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TOXICOLOGIC PATHOLOGY vol 29 no 6 pp 639ndash652 2001Copyright C 2001 by the Society of Toxicologic Pathology
Laboratory Animal amp Molecular Pathology
REVIEW ARTICLE
Compendium of Chemical Carcinogens by Target OrganResults of Chronic Bioassays in Rats Mice Hamsters Dogs and Monkeys
LOIS SWIRSKY GOLD12 NEELA B MANLEY1 THOMAS H SLONE1 AND JERROLD M WARD3
1Division of Biochemistry and Molecular Biology University of California Berkeley California 94720-32022Life Sciences Division Mail Stop 946 Ernest Orlando Lawrence Berkeley National Laboratory Berkeley California 94720 and
3Veterinary and Tumor Pathology Section Center for Cancer Research National Cancer Institute Frederick MD 21702-1201
ABSTRACT
A compendium of carcinogenesi s bioassay results organized by target organ is presented for 738 chemicals that are carcinogenic in chronic-exposure long-term bioassays in at least 1 species This compendium is based primarily on experiments in rats or mice results in hamsters monkeys and dogsare also reported The compendium can be used to identify chemicals that induce tumors at particular sites and to determine whether target sites arethe same for chemicals positive in more than 1 species The source of information is the Carcinogenic Potency Database (CPDB) which includesresults of 6073 experiments on 1458 chemicals (positive or negative for carcinogenicity) that have been reported in Technical Reports of the NationalCancer InstituteNational Toxicology Program or in papers in the general published literature The published CPDB includes detailed analyses of eachtest and citations The CPDB is publicly available in several formats (httppotencyberkeleyedu) Chemical carcinogens are reported for 35 differenttarget organs in rats or mice Target organs in humans are also summarized for 82 agents that have been evaluated as human carcinogens at a particulartarget site by the International Agency for Research on Cancer (IARC) Comparisons are provided of target organs for mutagens versus nonmutagensand rats versus mice
Keywords Human carcinogen tumor site animal cancer test Carcinogenic Potency Database species comparisons mutagenicity monkeys
INTRODUCTION
For many research issues in carcinogenesis it is valuableto have quick access to a list of chemicals that have been foundin chronic bioassays to induce tumors at each target site invarious species Researchers interested in carcinogenesis in aparticular target organ for example or epidemiologists inter-ested in a particular cancer in humans can use such results tocompare species or seek clues in animal models Comparisonof target sites in several species is possible for work on in-terspecies extrapolation Investigations of chemical structureor mechanism of carcinogenesis at a speci c target site canidentify chemicals that induce tumors in that organ
This paper presents a compendium of results of chroniclong-term cancer tests that is organized by the target or-gan of carcinogenesis (Table 1) Results are presented for738 chemicals that have been evaluated by the publishedauthor of experimental data as carcinogenic in at least oneexperiment in the Carcinogenic Potency Database (CPDB)(2 3 6) httppotencyberkeleyedudatabasehtml Resultsare organized by each of 35 target sites and within each
Address correspondenc e to Lois Swirsky Gold Mail Stop 946 E OLawrence Berkeley National Laboratory Berkeley California 94720 Fax(510) 547-7073 E-mail loispotencyberkeleyedu
site by the chemicals that induce tumors in each speciesThe compendium includes results of chronic bioassays inrats mice hamsters monkeys and dogs Comparative tox-icological analyses are facilitated by indicating whether achemical that is positive at a given site in the rat has beentested in the mouse whether results are also positive inthe mouse and whether the target organs are the same inthe 2 species By cross-referencing a chemical of interest tothe published plots of the CPDB (2 3 6) details of eachexperiment can be obtained including the number of ex-periments and strains tested as well as the following detailson each experiment citation of the original published paperstrain and sex of test animal route of chemical administra-tion dose rate tumor types tumor incidence the tumorigenicpotency (TD50) statistical signi cance and authorrsquos opinionTarget organs in humans are also summarized for 82 agentsthat have been evaluated as human carcinogens at a particulartarget site by the International Agency for Research on Cancer(IARC) (10 15 16) Comparisons of target organs for muta-gens versus nonmutagens and for rats versus mice are alsoprovided
METHODS
The CPDB (2 3 6) a systematic and unifying analysisof chronic long-term animal cancer tests is the source of
639 0192-623301$300 $000
640 GOLD ET AL TOXICOLOGIC PATHOLOGY
results included in the compendium (Table 1) The CPDBincludes 1381 papers published in the general literaturethrough 1996 and 430 Technical Reports of the NationalCancer InstituteNational Toxicology Program (NCINTP)published through 1998 Results are reported for 6073 ex-periments on 1458 chemicals of which 738 induce tumorsin 1 or more experiments
A word of caution is necessary about the limitations ofthe CPDB Only long-term experiments meeting a set of cri-teria designed to measure tumorigenic dose-rate (TD50) areincluded therefore the CPDB does not cover all cancer testsAdditionally for the identi cation of target sites for the com-pendium we do not personally evaluate whether a compoundinduced tumors at a given site rather the opinion of the pub-lished author is used For published opinions that are notclear even after personal communication with the publishedauthor the site is not considered a target and is not reportedin the compendium
Results of all NCINTP Technical Reports are included inthe CPDB except a few for which no whole body exposure inmgkgday could be calculated because the test agent was aparticulate or the route of administration was dermal (12 13)[httpntp-serverniehsnihgov] In the compendium a siteis classi ed as a target in an NCINTP bioassay if the eval-uation in the Technical Report was ldquocarcinogenicrdquo ldquoclearrdquoor ldquosomerdquo evidence of carcinogenic activity Sites that wereevaluated as ldquoequivocalrdquo are not included (9)
In the general literature experimental designs as well asthe authorsrsquo choice of information to report are quite diverseand bioassays have been included only if they meet all of thefollowing conditions
1 Animals on test were mammals2 Administration was begun early in life (100 days of age
or less for rats mice and hamsters)3 Route of administration was diet water gavage inhala-
tion intravenous or intraperitoneal injection (ie wherethe whole body was more likely to have been exposedrather than only a speci c site as with subcutaneous in-jection or skin painting)
4 Test agent was administered alone rather than in combi-nation with other chemicals
5 Exposure was chronic with not more than 7 days betweenadministrations
6 Duration of exposure was at least one fourth the standardlife span for that species For rodents the standard lifespan is 2 years
7 Duration of experiment was at least half the standard lifespan for that species
8 Research design included a concurrent control group9 Research design included at least 5 animals per group
10 Surgical intervention was not performed11 Pathology data were reported for the number of animals
with tumors rather than the total number of tumors12 Results reported were original data rather than sec-
ondary analyses of experiments already reported by otherauthors
More details on inclusion criteria can be found in Goldand coworkers (6) and httppotencyberkeleyedutextmethodshtml
Because we have adhered strictly to the standard inclu-sion criteria bioassays of particulate or brous matters arenot in the compendium eg asbestos cigarette smoke anddusts There are no studies using a single administration ofthe test agent no experiments by skin painting subcutaneousinjection or in utero exposure and no cocarcinogenesis ex-periments For a series of NCI long-term studies in monkeyssome of the inclusion rules have been relaxed details arereported in Appendix 1 of Gold et al 1999 (2)
There is great diversity in results for different chemicalsin the CPDB eg in the number of times a chemical has beentested among the 1148 chemicals tested in rats 25 haveonly 1 test in the CPDB and 50 have 2 tests however25 chemicals have 10 or more tests For the 938 chemicalstested in mice the parallel numbers are 11 with 1 test 57with 2 tests and 15 chemicals with more than 10 tests Ofthe 738 carcinogens reported here 54 (397738) have beentested in more than 1 species In the compendium (Table 1)a target site is identi ed by a positive result in any one ex-periment in the species thus different target sites may beidenti ed from the same or different experiments Chemi-cals that are tested more often have a greater chance of nd-ing multiple target sites Results on chemicals that have notbeen evaluated as carcinogenic are ignored in the target or-gan compendium (Table 1) however detailed results of thoseexperiments are reported in the plot of the CPDB (2 3 6)httppotencyberkeleyedu
Guide to the Compendium of Target Organs for 738Carcinogens
Table 1 reports results on 738 chemicals in the CPDB thatinduce tumors in at least 1 of 35 target organs in rats micehamsters monkeys or dogs The table is organized alpha-betically by target site and within each site by species andchemical Our previously unpublished analyses of experi-mental results that will be published in a forthcoming plot ofthe CPDB are included (3)
To facilitate use of the compendium the features aredescribed below using the example of adrenal gland whichis the rst of 35 target sites in Table 1 Under adrenal gland1 chemical is listed in hamsters 8 in mice and 16 in ratsIf a chemical name is followed by a superscript (either yor z) this indicates that the CPDB includes test results inboth rats and mice for example under adrenal gland in rats2-mercaptobenzothiazole but not isomazole has a super-script Because isomazole has no superscript it only hastests in the CPDB in the species reported in this case ratsThe superscript y for 2-mercaptobenzothiazole indicatesthat the chemical has been tested in both rats and mice butinduced tumors only in the reported species in this case ratsThe superscript z for 12-dibromo-3-chloropropane (DBCP)indicates that DBCP is carcinogenic at some target site inboth rats and mice Although the superscript z does not indi-cate whether DBCP induced tumors at the same target site inboth rats and mice this can easily be determined by lookingat mice under adrenal gland for the chemical name DBCPBecause it is not there DBCP induced tumors in mice only atsites other than the adrenal gland In contrastpentachloroanisole z induced adrenal tumors in both speciesbeacuse it is listed under that site for both species Bycomparing the chemicals with superscripts listed under each
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Adr
enal
glan
dH
amst
er1
Ure
than
ez
Mou
se8
Car
bon
tetr
achl
orid
ez F
uran
z 4
4-M
ethy
lene
dian
iline
2H
Clz
Pen
tach
loro
anis
olez
23
45
6-Pe
ntac
hlor
ophe
nol(
Dow
icid
eE
C-7
)y
23
45
6-P
enta
chlo
roph
enol
tec
hnic
algr
adez
p-R
osan
ilin
eH
Clz
11
2-T
rich
loro
etha
ney
Rat
16B
rom
oeth
anez
4-C
hlor
o-m
-phe
nyle
nedi
amin
ez C
obal
tsul
fate
hept
ahyd
rate
z 1
2-D
ibro
mo-
3-ch
loro
prop
anez
Die
thyl
stilb
estr
olz
Eth
ylal
coho
ly In
dolid
anI
som
azol
e2-
Mer
capt
oben
zoth
iazo
ley
Mir
exz
Pen
tach
loro
anis
olez
Phe
nolp
htha
lein
z 1
2-Pr
opyl
ene
oxid
ez C
Ip
igm
entr
ed3z
Res
erpi
nez
Ret
inol
acet
ate
Bon
eR
at5
Acr
onyc
ine
De
azac
ort
NN
-Dim
ethy
lani
liney
1-( 2
-Hyd
roxy
ethy
l)-1
-nit
roso
urea
z o-
Tolu
idin
eH
Clz
Clit
oral
pre
putia
lM
ouse
11A
ceta
ldeh
yde
met
hylf
orm
ylhy
draz
one
Ben
zene
z 1
3-B
utad
iene
z N
-n-B
utyl
-N-f
orm
ylhy
draz
ine
Dim
ethy
lvin
ylch
lori
dez
N-E
thyl
-N-f
orm
ylhy
draz
ine
glan
dH
exan
alm
ethy
lfor
myl
hydr
azon
e3-
Met
hylb
utan
alm
ethy
lfor
myl
hydr
azon
eP
enta
nalm
ethy
lfor
myl
hydr
azon
eN
-N-P
ropy
l-N
-for
myl
hydr
azin
eT
hio-
tepa
z
Rat
21A
cryl
amid
eC
Id
irec
tblu
e15
24
-Dia
min
oani
sole
sulf
atez
33
-Dim
etho
xybe
nzid
ine
2HC
l3
3-D
imet
hylb
enzi
dine
2H
Clz
Glu
-P-1
z G
lu-P
-2z
Gly
cido
lz IQ
z Is
opho
rone
y M
eIQ
xz 2-
Mer
capt
oben
zoth
iazo
ley
Nal
idix
icac
idy
15-
Nap
htha
lene
diam
inez
5-N
itro-
o-a
nisi
dine
z 5-
Nit
roac
enap
hthe
nez
p-N
itro
benz
oic
acid
y 1-
Nitr
opyr
ene
CI
aci
dre
d11
41
23-
Tri
chlo
ropr
opan
ez T
rp-P
-2ac
etat
ez
Ear
Zym
balrsquos
glan
dM
ouse
3B
enze
nez
Chl
orop
rene
z C
upfe
rron
z
Rat
41A
cryl
onit
rile
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
Azo
xym
etha
neB
enze
nez
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez C
Id
irec
tblu
e15
N-n
-But
yl-N
-nitr
osou
rea
Chl
oram
buci
lz C
upfe
rron
z N
-1-D
iace
tam
ido
uore
ne2
4-D
iam
inoa
niso
lesu
lfat
ez 3
3-D
ichl
orob
enzi
dine
25
-Dim
etho
xy-4
-am
inos
tilb
enez
33
-Dim
etho
xybe
nzid
ine
2HC
l3
3-D
imet
hylb
enzi
dine
2H
Clz
N-(
2-Fl
uore
nyl)
-22
2-t
riu
oroa
ceta
mid
eFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z G
lu-P
-1z
Glu
-P-2
z G
lyci
dolz
Hyd
razo
benz
enez
IQz
IQH
Cl
MeI
Qxz
2-M
etho
xy-3
-am
inod
iben
zofu
ran
8-M
etho
xyps
oral
enN
-(N
-Met
hyl-
N-n
itro
soca
rbam
oyl)
-l-o
rnit
hine
44
-Met
hyle
ne-
bis(
2-ch
loro
anili
ne)
5-N
itro-
o-an
isid
inez
5-N
itroa
cena
phth
enez
N-(
9-O
xo-2
-uo
reny
l)ac
etam
ide
Phen
acet
inz
Pre
dnim
usti
neC
Ia
cid
red
114
p-R
osan
iline
HC
lz T
hio-
tepa
z 4
4-T
hiod
iani
line
z b
-Thi
ogua
nine
deox
yrib
osid
e1
23-
Tri
chlo
ropr
opan
ez V
inyl
chlo
ride
z V
inyl
uor
idez
Eso
phag
usH
amst
er2
AF-
2z N
-Nitr
oso-
N-m
ethy
lure
than
eM
ouse
8B
enzo
( a) p
yren
ez 1
2-D
ibro
moe
than
ez N
-Eth
yl-N
-nit
ro-N
-nit
roso
guan
idin
eN
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
3-( 5
-Nit
ro-2
-fur
yl) -
imid
azo(
12-
a) p
yrid
inez
Nitr
osod
ibut
ylam
inez
N-N
itros
ohex
amet
hyle
neim
ine
Vin
ylac
etat
ez
Mon
key
1N
-Nitr
oso-
N-m
ethy
lure
az
Rat
362
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bis
( 23
-dib
rom
opro
pyl)
phos
phat
em
agne
sium
salt
N-n
-But
yl-N
-nitr
osou
rea
Dih
ydro
safr
olez
Dim
ethy
lvin
ylch
lori
dez
Din
itro
soho
mop
iper
azin
eZ
-Eth
yl-O
NN
-azo
xyet
hane
N-M
ethy
l-N
-nitr
o-N
-nit
roso
guan
idin
ez 3-
( 5-N
itro
-2-f
uryl
) -im
idaz
o(1
2-a
) pyr
idin
ez N
-Nitr
oso-
23-
dihy
drox
ypro
pyl-
2-hy
drox
ypro
pyla
min
eN
itro
so-2
3-d
ihyd
roxy
prop
yl-2
-oxo
prop
ylam
ine
N-N
itro
so-(
2-hy
drox
ypro
pyl)
-(2-
hydr
oxye
thyl
) am
ine
N-N
itros
o-N
-met
hyl-
4-u
oroa
nilin
eN
itros
o-N
-met
hyl-
N-(
2-ph
enyl
) eth
ylam
ine
Nitr
oso-
12
36-
tetr
ahyd
ropy
ridi
neN
-Nit
roso
( 22
2-t
riu
oroe
thyl
) eth
ylam
ine
N-N
itros
oall
yl-2
3-d
ihyd
roxy
prop
ylam
ine
N-N
itro
soal
lyl-
2-hy
drox
ypro
pyla
min
eN
-Nit
roso
ally
l-2-
oxop
ropy
lam
ine
Nitr
osoa
myl
uret
han
Nitr
osoa
naba
sine
N-N
itros
obis
( 2-h
ydro
xypr
opyl
) am
ine
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
diet
hyla
min
eN
-Nitr
osod
ipro
pyla
min
eN
itro
soet
hylu
reth
ane
Nit
roso
hept
amet
hyle
neim
ine
N-N
itro
som
ethy
l-2
3-di
hydr
oxyp
ropy
lam
ine
N-N
itros
omet
hyl-
2-hy
drox
ypro
pyla
min
eN
-Nit
roso
met
hyl(
2-ox
opro
pyl)
amin
e2-
Nitr
osom
ethy
lam
inop
yrid
ine
Nit
roso
met
hyla
nili
neN
-Nitr
oson
orni
cotin
e-1-
N-o
xide
N-N
itro
sopi
peri
dine
z N
-Nit
roso
thia
ldin
eN
-Nit
roso
thio
mor
phol
ine
Gal
lbla
dder
Ham
ster
1N
-Met
hyl-
N-f
orm
ylhy
draz
ine
Mou
se4
N-E
thyl
-N-f
orm
ylhy
draz
ine
N-M
ethy
l-N
-for
myl
hydr
azin
e3-
Met
hylb
utan
alm
ethy
lfor
myl
hydr
azon
eN
-N-P
ropy
l-N
-for
myl
hydr
azin
eM
onke
y1
Aa
toxi
nB
y 1H
arde
rian
glan
dM
ouse
19B
enze
nez
Ben
zidi
ne2
HC
l2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
13-
But
adie
nez
Cap
tafo
lz C
hlor
opre
nez
Cup
ferr
onz
Dic
hlor
oace
tyle
nez
Eth
ylen
eox
idez
Gen
tian
viol
etG
lyci
dolz
Iodi
nate
dgl
ycer
olz
Isop
rene
N-M
ethy
lola
cryl
amid
ey N
itro
met
hane
z 4
4-O
xydi
anil
inez
12
3-T
rich
loro
prop
anez
24
6-T
rini
tro-
13-
dim
ethy
l-5-
tert
-but
ylbe
nzen
eV
inyl
uor
idez
Hem
atop
oiet
icM
ouse
53A
ceta
mid
ez A
at
oxin
cru
dez
Ally
liso
vale
rate
z tr
ans-
5-A
min
o-3[
2-( 5
-nitr
o-2-
fury
l)vi
nyl] -
12
4-ox
adia
zole
2-A
min
o-4-
( p-n
itro
phen
yl) t
hiaz
ole
syst
em2-
Am
inoa
nthr
aqui
none
z 5-
Aza
cyti
dine
z A
zath
iopr
ine
Ben
zene
z 1
4-B
enzo
quin
one
Ben
zotr
ichl
orid
eB
enzo
ylhy
draz
ine
13-
But
adie
nez
12-
di-n
-But
ylhy
draz
ine
2HC
lC
apta
folz
Chl
oram
buci
lz C
hlor
inat
edpa
raf
ns( C
234
3ch
lori
ne)y
Cyc
loph
osph
amid
ez D
acar
bazi
nez
DD
Tz
Dib
rom
odul
cito
lz D
ibro
mom
anni
tolz
Est
radi
olm
usta
rdy
Eth
ylen
eox
idez
5-Fl
uoro
urac
ily Fo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z G
entia
nvi
olet
Hex
anam
idey
2-H
ydra
zino
-4-(
p-am
inop
heny
l)th
iazo
lez
2-H
ydra
zino
-4-
( p-n
itro
phen
yl) t
hiaz
olez
1-( 2
-Hyd
roxy
ethy
l)-1
-nit
roso
urea
z IC
RF
-159
z Is
opho
spha
mid
ez Is
opre
neM
eIQ
xz M
elph
alan
z 1-
Met
hyl-
14-
dihy
dro-
7-[ 2
-(5-
nitr
ofur
yl) v
inyl
] -4-
oxo-
18-
naph
thyr
idin
e-3-
carb
oxyl
ate
pota
ssiu
mM
ethy
lmet
hane
sulf
onat
e4
4-M
ethy
lene
dian
ilin
e2H
Clz
Met
roni
dazo
lez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez P
hene
ster
inz
Phe
nolp
htha
lein
z Ph
IPH
Clz
Phor
bol
Proc
arba
zine
HC
lz S
trob
ane
Tetr
auo
roet
hyle
nez
Thi
o-te
paz
p-To
lylu
reay
Tri
s(2-
chlo
roet
hyl)
phos
phat
ez U
reth
anez
CI
vat
yello
w4y
( Con
tinue
don
next
page
)
641
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Mon
key
1P
roca
rbaz
ine
HC
lz
Rat
56A
llyl
isov
aler
atez
1-A
myl
-1-n
itros
oure
aA
traz
iney
Ben
zidi
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
CI
dir
ectb
lue
15
N-n
-But
yl-N
-nitr
osou
rea
Cad
miu
mch
lori
deC
hlor
ambu
cilz
Cyc
loph
osph
amid
ez D
acar
bazi
nez
13-
Dib
utyl
-1-n
itro
sour
eaD
ichl
oroa
cety
lene
z 3
3-D
ichl
orob
enzi
dine
Dic
hlor
vosz
Dim
etho
xane
33
-Dim
etho
xybe
nzid
ine-
44
-dii
socy
anat
ey 3
3-D
imet
hoxy
benz
idin
e2H
Cl
Dim
ethy
lmor
phol
inop
hosp
hora
mid
atey
2-( 2
2-D
imet
hylh
ydra
zino
) -4-
( 5-n
itro-
2-fu
ryl)
thia
zole
Eth
ylen
eox
idez
Form
alde
hyde
z Fo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z F
uran
z G
lyci
dolz
FD
ampC
gree
nno
1y
FDamp
Cgr
een
no2
y H
emat
oxyl
in2
-Hyd
razi
no-4
-(p-
amin
ophe
nyl)
thia
zole
z H
ydro
quin
onez
1-( 2
-Hyd
roxy
ethy
l)-1
-nit
roso
urea
z Io
dina
ted
glyc
erol
z L
asio
carp
ine
2-M
erca
ptob
enzo
thia
zole
y M
etep
aM
ethy
lter
t-bu
tyle
ther
z M
irex
z l-
5-M
orph
olin
omet
hyl-
3-[(
5-ni
trof
urfu
ryli
dene
) am
ino]
-2-o
xazo
lidi
none
H
Cl
Nit
rite
sod
ium
y N
-[5-
( 5-N
itro-
2-fu
ryl)
-13
4-t
hiad
iazo
l-2-
yl] a
ceta
mid
ez o-
Nit
roan
isol
ez 1-
[(5-
Nitr
ofur
fury
liden
e)am
ino]
-2-i
mid
azol
idin
one
1-N
itro
pyre
neN
itros
o-N
-met
hyl-
N-(
2-ph
enyl
) eth
ylam
ine
N-N
itros
odie
than
olam
ine
PhIP
HC
lz P
roca
rbaz
ine
HC
lz P
ropa
nesu
ltone
N-P
ropy
l-N
-nit
roso
urea
FD
ampC
red
no2
FD
ampC
red
no4
y Te
trac
hlor
oeth
ylen
ez Te
tra
uoro
ethy
lene
z T
hio-
tepa
z 2
46-
Tri
chlo
roph
enol
z T
rp-P
-2ac
etat
ez
Kid
ney
Ham
ster
1B
rom
ate
pota
ssiu
mz
Mou
se26
o-B
enzy
l-p-
chlo
roph
enol
y 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bro
mat
epo
tass
ium
z B
rom
odic
hlor
omet
hane
z 1
3-B
utad
iene
z 1
2-di
-n-B
utyl
hydr
azin
e2H
Cl
Caf
feic
acid
z C
hlor
ofor
mz
Chl
orop
rene
z D
amin
ozid
ez 2
4-D
iam
inop
heno
l2H
Cly
Dic
hlor
oace
tyle
nez
24-
Din
itrot
olue
ne( c
onta
inin
g1
0-1
52
6-di
nitr
otol
uene
)zH
ydro
quin
onez
N-H
ydro
xy-2
-ace
tyla
min
ouo
rene
z 3-
Hyd
roxy
-p-b
utyr
ophe
neti
dide
L
ead
acet
ate
basi
cz M
ercu
rym
ethy
lchl
orid
eN
itril
otri
acet
icac
idz
Och
rato
xin
Az
Phe
nace
tinz
CI
pig
men
tred
3z St
rept
ozot
ocin
z T
ris(
2-ch
loro
ethy
l)ph
osph
atez
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez V
inyl
iden
ech
lori
dey
Mon
key
1C
ycas
inan
dm
ethy
lazo
xym
etha
nola
ceta
teR
at86
A
atox
inB
1y 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 1-
Am
ino-
2-m
ethy
lant
hraq
uino
nez
2-A
min
o-5-
( 5-n
itro-
2-fu
ryl)
-13
4-o
xadi
azol
e2-
Am
ino-
5-( 5
-nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
e2-
Am
ino-
4-ni
trop
heno
ly 2-
Am
ino-
5-ni
trot
hiaz
oley
o-A
nisi
dine
HC
lz A
rist
oloc
hic
acid
so
dium
salt
( 77
AA
I21
A
AII
) A
zoxy
met
hane
Bar
bita
lso
dium
Ben
zofu
ranz
Bro
mat
epo
tass
ium
z B
rom
odic
hlor
omet
hane
z te
rt-B
utyl
alco
holz
Caf
feic
acid
z C
apta
folz
Cap
tanz
Chl
orin
ated
para
fns
( C12
60
chlo
rine
)zC
hlor
ofor
mz
3-( p
-Chl
orop
heny
l)-1
1-d
imet
hylu
reay
Chl
orop
rene
z C
hlor
otha
loni
ly C
inna
myl
anth
rani
late
z C
itrin
inC
oum
arin
z D
ichl
oroa
cety
lene
z 1
4-D
ichl
orob
enze
nez
Die
thyl
acet
amid
e3
4-D
ihyd
roco
umar
inz
Dim
etho
xane
Dim
ethy
lmet
hylp
hosp
hona
tey
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
N-4
-(4
-Flu
orob
iphe
nyl)
acet
amid
eFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z G
lyci
neH
exac
hlor
obut
adie
ne
Hex
achl
oroe
than
ez H
exam
ethy
lmel
amin
e2-
Hyd
razi
no-4
-(5-
nitr
o-2-
fury
l)th
iazo
lez
Hyd
roqu
inon
ez 1-
( 2-H
ydro
xyet
hyl)
-1-n
itro
sour
eaz
Isop
horo
ney
Lea
dac
etat
ey L
ead
acet
ate
basi
cz d-
Lim
onen
ey 2-
Met
hoxy
-3-a
min
odib
enzo
fura
n8-
Met
hoxy
psor
alen
Z-M
ethy
l-O
NN
-azo
xyet
hane
Met
hylt
ert-
buty
leth
erz
N-(
N-M
ethy
l-N
-nit
roso
carb
amoy
l)-l
-orn
ithi
nea
-Met
hylb
enzy
lalc
ohol
y M
irex
z l-
5-M
orph
olin
omet
hyl-
3-[(
5-ni
trof
urfu
rylid
ene)
amin
o]-2
-oxa
zolid
inon
eH
Cl
Nit
rilo
tria
ceti
cac
idz
Nit
rilo
tria
cetic
acid
tri
sodi
umsa
ltm
onoh
ydra
tey
3-( 5
-Nitr
o-2-
fury
l)-i
mid
azo(
12-
a) p
yrid
inez
N-[
3-( 5
-Nitr
o-2-
fury
l)-1
24
-oxa
diaz
ole-
5-yl
] -m
ethy
l]ac
etam
ide
N-[
5-( 5
-Nitr
o-2-
fury
l)-1
34
-thi
adia
zol-
2-yl
] ace
tam
idez
o-N
itro
anis
olez
Nitr
oben
zene
z 2-
Nit
ro
uore
ne
1-[(
5-N
itrof
urfu
rylid
ene)
amin
o]hy
dant
oinz
1-N
itro
so-1
-hyd
roxy
ethy
l-3-
chlo
roet
hylu
rea
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
diet
hyla
min
eN
-Nitr
osod
imet
hyla
min
ez N
-Nit
roso
pyrr
olid
inez
Och
rato
xin
Az
CI
aci
dor
ange
3y N
-Oxy
diet
hyle
neth
ioca
rbam
yl-N
-oxy
diet
hyle
nesu
lfen
amid
eP
hena
cetin
z Ph
enaz
one
Phen
olph
thal
einz
Phen
ylbu
tazo
nez
o-Ph
enyl
phen
ate
sodi
umy
Que
rcet
iny
Salic
ylaz
osul
fapy
ridi
nez
Str
epto
zoto
cinz
Tetr
achl
oroe
thyl
enez
Tetr
auo
roet
hyle
nez
Tetr
ahyd
rofu
ranz
12
3-T
rich
loro
prop
anez
Tri
s(2-
chlo
roet
hyl)
phos
phat
ez T
ris(
23-
dibr
omop
ropy
l)ph
osph
atez
Vin
ylch
lori
dez
Lar
gein
test
ine
Ham
ster
51
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
Hyd
razi
nez
Met
hylh
ydra
zine
Ure
than
ezM
ouse
1C
apsa
icin
Rat
32A
at
oxin
B1y
1-A
llyl
-1-n
itros
oure
a1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z A
myl
opec
tin
sulf
ate
Azo
xym
etha
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
te
chni
calg
rade
z C
Id
irec
tblu
e15
Bro
mod
ichl
orom
etha
nez
N-N
-But
yl-n
-nitr
osou
rea
Car
rage
enan
aci
d-de
grad
edC
hrys
azin
z D
extr
ansu
lfat
eso
dium
( DS-
M-1
) 3
3-D
imet
hoxy
benz
idin
e2H
Cl
33
-Dim
ethy
lben
zidi
ne2
HC
lz Z
-Eth
yl-O
NN
-azo
xym
etha
ne1
-Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-t
hiaz
olyl
] hyd
razi
dez
Glu
-P-1
z G
lu-P
-2z
Gly
cido
lz N
-Hex
ylni
tros
oure
a1-
Hyd
roxy
anth
raqu
inon
e1-
( 2-H
ydro
xyet
hyl)
-1-n
itro
sour
eaz
IQz
o-N
itro
anis
olez
N-N
itro
sobi
s(2-
oxop
ropy
l)am
ine
Phe
nazo
pyri
dine
HC
lz P
hIP
HC
lz C
Ia
cid
red
114
44
-Thi
odia
nilin
ez T
ribr
omom
etha
ney
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez
Liv
erD
og2
33
-Dic
hlor
oben
zidi
ne4
4-M
ethy
lene
-bis
( 2-c
hlor
oani
line
)H
amst
er16
2-A
cety
lam
ino
uore
nez
pp
-DD
Ey
12-
Dim
ethy
lhyd
razi
ne2
HC
lH
exac
hlor
oben
zene
z H
ydra
zine
sulf
atez
N-H
ydro
xy-2
-ace
tyla
min
ouo
rene
z N
-Met
hyl-
N-f
orm
ylhy
draz
ine
Met
hylh
ydra
zine
Met
hyln
itros
amin
o-N
N-d
imet
hyle
thyl
amin
eN
-Nitr
oso-
13-
oxaz
olid
ine
Nit
roso
-2-o
xopr
opyl
etha
nola
min
eN
-Nitr
osoa
llyl-
2-ox
opro
pyla
min
eN
-Nit
roso
azet
idin
eN
-Nit
roso
mor
phol
ine
N-N
itros
opip
erid
inez
N-N
itros
opyr
rolid
inez
Mou
se23
1A
-a-C
Ace
tam
inop
henz
2-A
cety
lam
ino
uore
nez
Aci
uor
fen
Ald
rinz
1-A
min
o-2
4-di
brom
oant
hraq
uino
nez
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
1-A
min
o-2-
met
hyla
nthr
aqui
none
z 2-
Am
inoa
nthr
aqui
none
z 4-
Am
inod
iphe
nyl
2-A
min
odip
heny
lene
oxid
e3-
Am
inot
riaz
olez
Ara
mite
z A
rocl
or12
54y
Aur
amin
e-O
z B
enzi
dine
2H
Cl
Ben
zofu
ranz
Ben
zyla
ceta
tey
3-B
enzy
lsyd
none
-4-a
ceta
mid
ez B
is( 2
-chl
oro-
1-m
ethy
leth
yl) e
ther
tec
hnic
algr
adey
Bis
-2-c
hlor
oeth
ylet
her
Bis
-2-h
ydro
xyet
hyld
ithio
carb
amic
acid
pot
assi
umC
Id
irec
tbla
ck38
CI
dir
ectb
lue
218z
HC
blue
no1
z H
Cbl
ueno
1( p
uri
ed)
Bro
mod
ichl
orom
etha
nez
13-
But
adie
nez
But
ylat
edhy
drox
ytol
uene
y 1
1-di
-n-B
utyl
hydr
azin
eC
apta
folz
Car
bazo
le
Car
bon
tetr
achl
orid
ez C
hlor
alhy
drat
eC
hlor
ambe
ny C
hlor
dane
tec
hnic
algr
adey
Chl
oren
dic
acid
z C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
1-
Chl
oro-
2-ni
trob
enze
ney
1-C
hlor
o-4-
nitr
oben
zene
y 4-
Chl
oro-
m-p
heny
lene
diam
inez
4-C
hlor
o-o-
phen
ylen
edia
min
ez 5-
Chl
oro-
o-to
luid
iney
642
[ 4-C
hlor
o-6-
( 23
-xyl
idin
o)-2
-pyr
imid
inyl
thio
] ace
ticac
idz
4-C
hlor
o-6-
( 23
-xyl
idin
o)-2
-pyr
imid
inyl
thio
( N-b
-hyd
roxy
ethy
l)ac
etam
idez
Chl
oroa
ceta
ldeh
yde
p-C
hlor
oani
line
HC
lz C
hlor
oben
zila
tey
Chl
orod
ibro
mom
etha
ney
Chl
orof
orm
z C
hlor
opre
nez
Chr
ysaz
inz
CI-
924
Cin
nam
ylan
thra
nila
tez
Cip
ro
brat
ez C
lobu
zari
ty C
ompo
und
LY17
1883
Cou
mar
inz
p-C
resi
dine
z C
upfe
rron
z C
ycla
mat
eso
dium
y C
yclo
chlo
roti
neC
ypro
tero
neac
etat
ep
p-D
DD
y p
p-D
DE
y D
DT
z D
ialla
te2
4-D
iam
inot
olue
nez
24-
Dia
min
otol
uene
2H
Clz
35-
Dic
hlor
o-( N
-11
-dim
ethy
l-2-
prop
ynyl
) ben
zam
ide
26-
Dic
hlor
o-p-
phen
ylen
edia
min
ey D
ichl
oroa
cetic
acid
z 1
4-D
ichl
orob
enze
nez
12-
Dic
hlor
opro
pane
y D
icof
oly
Die
ldri
nz D
ifta
lone
34
-Dih
ydro
coum
arin
z D
ihyd
rosa
frol
ez 2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 1
1-D
imet
hylh
ydra
zine
y 1
4-D
ioxa
nez
55-
Dip
heny
lhyd
anto
iny
Dip
yron
ey D
oxyl
amin
esu
ccin
atez
Est
rago
led
l-E
thio
nine
z o-
Eth
oxyb
enza
mid
eN
-Eth
yl-N
-for
myl
hydr
azin
eE
thyl
ene
imin
eE
thyl
ene
thio
urea
z 2-
Eth
ylhe
xano
ly di
( 2-E
thyl
hexy
l)ad
ipat
ey di
( 2-E
thyl
hexy
l)ph
thal
atez
4-F
luor
o-4-
amin
odip
heny
lF
uran
z Fu
rfur
alz
Gen
tian
viol
etG
lu-P
-1z
Glu
-P-2
z G
lyci
dolz
Gri
seof
ulvi
nH
CD
Dm
ixtu
rez
Hep
tach
lory
Hex
achl
orob
enze
nez
a-1
23
45
6-H
exac
hlor
ocyc
lohe
xane
z b
-12
34
56
-Hex
achl
oroc
yclo
hexa
nec
-12
34
56
-Hex
achl
oroc
yclo
hexa
ney
Hex
achl
oroc
yclo
hexa
ne
tech
nica
lgra
deH
exac
hlor
oeth
anez
Hex
anal
met
hylf
orm
ylhy
draz
one
Hyd
razi
nesu
lfat
ez H
ydra
zobe
nzen
ez H
ydro
quin
onez
N-H
ydro
xy-2
-ac
etyl
amin
ouo
rene
z 1
-Hyd
roxy
estr
agol
e2-
Hyd
roxy
ethy
lhyd
razi
ne1
-Hyd
roxy
safr
olez
IQz
Ison
iazi
dz Is
opre
neK
epon
ez L
eupe
ptin
Lov
asta
tinL
uteo
skyr
inM
alon
alde
hyde
sod
ium
saltz
MeA
-a-C
acet
atez
MeI
QM
eIQ
xz M
ethi
dath
ion
3-M
etho
xy-4
-am
inoa
zobe
nzen
eM
ethy
lter
t-bu
tyle
ther
z M
ethy
lclo
fena
pate
z N
-Met
hyl-
N-f
orm
ylhy
draz
ine
3-M
ethy
lbut
anal
met
hylf
orm
ylhy
draz
one
44
-Met
hyle
ne-b
is( 2
-chl
oroa
nili
ne)
2HC
ly M
ethy
lene
chlo
ride
z 4
4-M
ethy
lene
bis(
NN
-dim
ethy
l)be
nzen
amin
ez 4
4-M
ethy
lene
dian
iline
2H
Clz
Met
hylh
ydra
zine
N-M
ethy
lola
cryl
amid
ey M
ethy
lphe
nida
teH
Cly
Mic
hler
rsquoske
tone
z M
irex
z 1
5-N
apht
hale
nedi
amin
ez 2-
Nap
hthy
lam
inez
Nit
hiaz
idez
3-N
itro-
p-ac
etop
hene
tidey
5-N
itro-
o-an
isid
inez
2-N
itro
-p-p
heny
lene
diam
iney
5-N
itro
-o-t
olui
dine
y 5-
Nitr
oace
naph
then
ez o-
Nitr
oani
sole
z N
itrob
enze
nez
6-N
itrob
enzi
mid
azol
ey N
itro
fenz
Nit
rom
etha
nez
Nitr
osod
ibut
ylam
inez
N-N
itros
odim
ethy
lam
inez
p-N
itros
odip
heny
lam
inez
N-N
itro
sohe
xam
ethy
lene
imin
eN
-Nit
roso
pipe
ridi
nez
Non
abro
mob
iphe
nyl
Och
rato
xin
Az
Oxa
zepa
my
44
-Oxy
dian
iline
z Pe
ntac
hlor
oeth
aney
Pent
achl
oron
itrob
enze
ney
23
45
6-Pe
ntac
hlor
ophe
nol(
Dow
icid
eE
C-7
)y 2
34
56-
Pen
tach
loro
phen
olt
echn
ical
grad
ez P
enta
nalm
ethy
lfor
myl
hydr
azon
eP
hena
zopy
ridi
neH
Clz
Phe
noba
rbit
aly
Phen
obar
bita
lso
dium
z Ph
enyl
buta
zone
z o-
Phen
ylen
edia
min
e2H
Clz
Pipe
rony
l-bu
toxi
dez
Pipe
rony
lsul
foxi
dey
Poly
brom
inat
edbi
phen
ylm
ixtu
rez
Prob
enec
idy
N-N
-Pro
pyl-
N-f
orm
ylhy
draz
ine
Damp
Cre
dno
5z
Rif
ampi
ciny
Rip
azep
amy
p-R
osan
iline
HC
lz S
afro
lez
Sali
cyla
zosu
lfap
yrid
inez
Sel
eniu
mdi
ethy
ldith
ioca
rbam
ate
Sel
eniu
msu
lde
z S
trob
ane
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
11
12-
Tetr
achl
oroe
than
ey 1
12
2-Te
trac
hlor
oeth
aney
Tetr
achl
oroe
thyl
enez
Tetr
achl
orvi
npho
sy Te
tra
uoro
-m-p
heny
lene
diam
ine
2HC
ly Te
tra
uoro
ethy
lene
z Te
trah
ydro
fura
nz T
hioa
ceta
mid
ez 4
4-T
hiod
iani
linez
Thi
oura
cilz
Tolu
ene
diis
ocya
nate
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
m-T
olui
dine
HC
ly o-
Tolu
idin
eH
Clz
p-To
luid
ine
HC
ly To
xaph
eney
T-2
toxi
nT
riam
tere
ney
Tri
chlo
roac
etic
acid
y 2
46-
Tri
chlo
roan
iline
y 1
12-
Tri
chlo
roet
hane
y T
rich
loro
ethy
lene
z T
rich
loro
ethy
lene
( wit
hout
epic
hlor
ohyd
rin)
y 2
46-
Tri
chlo
roph
enol
z 1
23-
Tri
chlo
ropr
opan
ez T
ri
ural
int
echn
ical
grad
ey 2
45-
Tri
met
hyla
nili
nez
24
5-T
rim
ethy
lani
line
HC
lz 2
46-
Tri
met
hyla
nilin
eH
Clz
24
6-T
rini
tro-
13-
dim
ethy
l-5-
tert
-but
ylbe
nzen
eT
ris(
2-ch
loro
ethy
l)ph
osph
atez
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez T
ris(
2-et
hylh
exyl
) pho
spha
tey
Trp
-P-1
acet
atez
Trp
-P-2
acet
atez
Ure
than
ez V
inyl
carb
amat
eV
inyl
uo
ride
z 2
5-X
ylid
ine
HC
lz C
Id
ispe
rse
yell
ow3z
Zea
rale
none
y
Mon
key
8A
ato
xin
B1y
Cyc
asin
and
met
hyla
zoxy
met
hano
lace
tate
IQ
z N
-Nitr
osod
ieth
ylam
ine
N-N
itro
sodi
prop
ylam
ine
N-N
itro
sopi
peri
dine
z S
teri
gmat
ocys
tinz
Ure
than
ez
Rat
206
Ace
tam
idez
Ace
tam
inop
henz
Ace
toxi
me
2-A
cety
lam
ino
uore
nez
A
atox
icol
A
atox
inB
y 1A
at
oxin
cru
dez
1-A
min
o-2
4-di
brom
oant
hraq
uino
nez
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
1-A
min
o-2-
met
hyla
nthr
aqui
none
z 2-
Am
inoa
nthr
aqui
none
z o-
Am
inoa
zoto
luen
ey 11
-Am
inou
ndec
anoi
cac
idy
Ara
mit
ez A
rocl
or12
60A
uram
ine-
Oz
Azo
xym
etha
neB
emit
radi
ne
Ben
zidi
ne3
-Ben
zyls
ydno
ne-4
-ace
tam
idez
Bis
( 23
-dib
rom
opro
pyl)
phos
phat
em
agne
sium
salt
CI
dir
ectb
lue
15
Bro
mod
ichl
orom
etha
nez
Bud
eson
ide
Cap
tafo
lz C
arbo
nte
trac
hlor
idez
Chl
oren
dic
acid
z C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
4-C
hlor
o-4
-am
inod
iphe
nyle
ther
z 2-
Chl
oro-
5-( 3
5-d
imet
hylp
iper
idin
osul
phon
yl) b
enzo
icac
id[
4-C
hlor
o-6-
( 23
-xy
lidi
no) -
2-py
rim
idin
ylth
io] a
ceti
cac
idz
4-C
hlor
o-6-
( 23
-xyl
idin
o)-2
-pyr
imid
inyl
thio
( N-b
-hyd
roxy
ethy
l)ac
etam
idez
Chl
orob
enze
ney
Chl
orof
orm
z 3-
( p-C
hlor
ophe
nyl)
-11
-dim
ethy
lure
ay C
ipro
bra
tez
Cliv
orin
eC
lob
rate
y C
loph
enA
30C
oum
arin
z p-
Cre
sidi
nez
Cro
tona
ldeh
yde
Cup
ferr
onz
Cyc
lope
ntan
one
oxim
eD
DT
z D
ecab
rom
odip
heny
loxi
dey
Deh
ydro
epia
ndro
ster
one
Deh
ydro
epia
ndro
ster
one
acet
ate
24-
Dia
min
otol
uene
z 2
4-D
iam
inot
olue
ne2
HC
lz 1
2-D
ibro
moe
than
ez D
ichl
oroa
ceti
cac
idz
Dic
hlor
oace
tyle
nez
NN
-Die
thyl
-4-(
4-[
pyri
dyl-
1-o
xide
] azo
) ani
line
Die
thyl
stil
best
rolz
Dim
etho
xane
3
3-D
imet
hoxy
benz
idin
e2H
Cl
56-
Dim
etho
xyst
erig
mat
ocys
tinN
N-D
imet
hyl-
4-am
inoa
zobe
nzen
e6-
Dim
ethy
lam
ino-
44-
diph
enyl
-3-h
epta
nola
ceta
teH
Cly
33
-Dim
ethy
lben
zidi
ne2
HC
lz D
imet
hyln
itram
ine
Din
itros
ohom
opip
eraz
ine
26-
Din
itro
tolu
ene
24-
Din
itrot
olue
ne( c
onta
inin
g1
0-1
52
6-di
nitr
otol
uene
)z
Din
itrot
olue
net
echn
ical
grad
e( 2
4( 7
7) -
and
26
( 19
) -)
14-
Dio
xane
z D
ipen
tyln
itro
sam
ine
Dox
ylam
ine
succ
inat
ez E
thin
yles
trad
iol
Eth
ioni
ne
dl-E
thio
nine
z 4-
Eth
oxy-
phen
ylur
eaE
thyl
alco
holy
Z-E
thyl
-ON
N-a
zoxy
etha
neZ
-Eth
yl-O
NN
-azo
xym
etha
neE
thyl
ene
thio
urea
z di
( 2-E
thyl
hexy
l)ph
thal
atez
Flu
cona
zole
y N
-(2-
Flu
oren
yl) -
22
2-tr
iuo
roac
etam
ide
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-t
hiaz
olyl
] hyd
razi
dez
Fum
onis
inB
1F
uran
z Fu
rfur
alz
Glu
-P-1
z G
lu-P
-2z
FDamp
Cgr
een
no1
y H
CD
Dm
ixtu
rez
Hex
achl
orob
enze
nez
a-1
23
45
6-H
exac
hlor
ocyc
lohe
xane
z H
ydra
zine
z H
ydra
zine
sulf
atez
Hyd
razo
benz
enez
Hyd
roch
loro
uor
ocar
bon
123
N-H
ydro
xy-2
-ace
tyla
min
ouo
rene
z 1-
Hyd
roxy
anth
raqu
inon
e1-
( 2-H
ydro
xyet
hyl)
-nitr
oso-
3-ch
loro
ethy
lure
a1
-Hyd
roxy
safr
olez
IQz
IQH
Cl
Ison
iazi
dz K
epon
ez L
asio
carp
ine
MeA
-a-C
acet
atez
MeI
Qxz
Met
hapy
rile
neH
Cl
Z-M
ethy
l-O
NN
-azo
xyet
hane
Met
hylc
arba
mat
ey M
ethy
lclo
fena
pate
z 3
-Met
hyl-
4-di
met
hyla
min
oazo
benz
ene
2-M
ethy
l-1-
nitr
oant
hraq
uino
nez
4-( 4
-N-M
ethy
l-N
-nit
rosa
min
osty
ryl)
quin
olin
e4
4-M
ethy
lene
-bis
( 2-c
hlor
oani
line
) 4
4-M
ethy
lene
-bis
( 2-m
ethy
lani
line
) 4
4-M
ethy
lene
dian
ilin
e2H
Clz
4-( M
ethy
lnit
rosa
min
o)-1
-(3-
pyri
dyl)
-1-(
buta
none
) M
etro
nida
zole
z M
ichl
errsquos
keto
nez
Mir
exz
Mon
ocro
tali
neN
afen
opin
Nit
rite
sod
ium
y N
itrob
enze
nez
2-N
itro
buta
ne2
-Nit
ro
uore
ne3
-Nit
rope
ntan
eN
-Nitr
oso-
bis-
( 44
4-t
ri
uoro
-N-b
utyl
) am
ine
1-N
itros
o-5
6-di
hydr
oura
cil
N-N
itro
so-2
3-d
ihyd
roxy
prop
ylet
hano
lam
ine
1-N
itros
o-1-
hydr
oxye
thyl
-3-c
hlor
oeth
ylur
ea1
-Nitr
oso-
1-( 2
-hyd
roxy
prop
yl) -
3-ch
loro
ethy
lure
aN
-Nitr
oso-
( 2-h
ydro
xypr
opyl
) -( 2
-hyd
roxy
ethy
l)am
ine
N-N
itros
o-N
-met
hyl-
N-d
odec
ylam
ine
Nit
roso
-N-m
ethy
l-N
-(2-
phen
yl) e
thyl
amin
e
( Con
tinue
don
next
page
)
643
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
N-N
itro
so-N
-met
hyld
ecyl
amin
e3-
Nit
roso
-2-o
xazo
lidin
one
Nit
roso
-2-o
xopr
opyl
etha
nola
min
eN
itro
so-1
23
6-t
etra
hydr
opyr
idin
eN
-Nit
roso
ally
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itro
soal
lyl-
2-ox
opro
pyla
min
eN
-Nitr
osoa
llyl
etha
nola
min
eN
-Nit
roso
bis(
2-ox
opro
pyl)
amin
eN
itro
sodi
buty
lam
inez
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
diet
hyla
min
eN
-Nitr
osod
imet
hyla
min
ez p-
Nitr
osod
iphe
nyla
min
ez N
-Nit
roso
dipr
opyl
amin
eN
itros
odod
ecam
ethy
lene
imin
eN
-Nit
roso
ephe
drin
eN
itro
soet
hylm
ethy
lam
ine
Nitr
osoh
epta
met
hyle
neim
ine
N-N
itros
omet
hyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nit
roso
met
hyl-
( 2-h
ydro
xyet
hyl)
amin
eN
-Nitr
osom
ethy
l-( 3
-hyd
roxy
prop
yl) a
min
eN
-Nitr
osom
ethy
l(2-
oxop
ropy
l)am
ine
N-N
itro
som
ethy
l-( 2
-tos
ylox
yeth
yl) a
min
eN
itro
som
ethy
lund
ecyl
amin
eN
-Nit
roso
mor
phol
ine
N-N
itros
opip
erid
inez
N-N
itro
sopy
rrol
idin
ez N
-Nit
roso
thia
ldin
eo-
Nit
roso
tolu
ene
Nor
lest
rinz
N-(
9-O
xo-2
-uo
reny
l)ac
etam
ide
44
-Oxy
dian
iline
z 2
34
56-
Pent
achl
orop
heno
lte
chni
calg
rade
z P
etas
iten
ine
Phe
noba
rbit
als
odiu
mz
1-P
heny
lazo
-2-n
apht
holy
o-P
heny
lene
diam
ine
2HC
lz P
iper
onyl
buto
xide
z P
olyb
rom
inat
edbi
phen
ylm
ixtu
rez
Pre
dnis
olon
eP
yril
amin
em
alea
tey
CI
aci
dre
d11
4C
Ip
igm
entr
ed3z
Damp
Cre
dno
5z
Damp
Cre
dno
9y
FD
ampC
red
no1
p-
Ros
anili
neH
Clz
Saf
role
z Se
leni
umsu
lde
z Se
nkir
kine
Ste
rigm
atoc
ystin
z S
ymph
ytin
eTa
mox
ifen
citr
atez
Telo
neII
tec
hnic
algr
adez
33
44
-Te
traa
min
obip
heny
l4H
Clz
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tetr
auo
roet
hyle
nez
Thi
oace
tam
idez
44
-Thi
odia
nilin
ez To
luen
edi
isoc
yana
te
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
Tri
amci
nolo
neac
eton
ide
24
5-T
rim
ethy
lani
line
z 2
45-
Tri
met
hyla
nili
neH
Clz
24
6-T
rim
ethy
lani
line
HC
lz T
rini
trog
lyce
rin
Trp
-P-1
acet
atez
Trp
-P-2
acet
atez
Vin
ylac
etat
ez V
inyl
brom
ide
Vin
ylch
lori
dez
Vin
yl
uori
dez
CI
dis
pers
eye
llow
3z
Tre
esh
rew
1A
ato
xin
B1y
Lun
gH
amst
er3
Met
hyln
itro
sam
ino-
NN
-dim
ethy
leth
ylam
ine
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
1-N
itro
so-3
45
-tri
met
hylp
iper
azin
eM
ouse
116
Ace
tald
ehyd
em
ethy
lfor
myl
hydr
azon
eN
-Ace
tyl-
4-( h
ydro
xym
ethy
l)ph
enyl
hydr
azin
e1-
Ace
tyl-
2-is
onic
otin
oylh
ydra
zine
A
llyl
hydr
azin
eH
Cl
1-A
min
o-2
4-di
brom
oant
hraq
uino
nez
Are
coli
neH
Cl
5-A
zacy
tidi
nez
Ben
zene
z B
enzo
fura
nz B
enzo
tric
hlor
ide
Ben
zoyl
hydr
azin
eB
enzy
lhyd
razi
ne2
HC
l2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bis
( 2-c
hlor
o-1-
met
hyle
thyl
) eth
er
tech
nica
lgra
dey
Bis
-(ch
loro
met
hyl)
ethe
rz 1
3-B
utad
iene
z N
-n-B
utyl
-N-f
orm
ylhy
draz
ine
But
ylat
edhy
drox
ytol
uene
y 1
1-di
-n-B
utyl
hydr
azin
en-
But
ylhy
draz
ine
HC
l1
2-di
-N-B
utyl
hydr
azin
e2H
Cl
Caf
feic
acid
z C
arba
myl
hydr
azin
eH
Cl
1-C
arba
myl
-2-p
heny
lhyd
razi
neC
hlor
ambu
cilz
Chl
orop
rene
z C
obal
tsul
fate
hept
ahyd
rate
z C
oum
arin
z C
yclo
phos
pham
idez
Dac
arba
zine
z D
amin
ozid
ez p
p-D
DD
y D
DT
z 1
1-D
iall
ylhy
draz
ine
12-
Dia
llyl
hydr
azin
e2H
Cl
Dib
enz(
ah)
anth
race
ne1
2-D
ibro
mo-
3-ch
loro
prop
anez
Dib
rom
odul
cito
lz 1
2-D
ibro
moe
than
ez D
ibro
mom
anni
tolz
12-
Dic
hlor
oeth
anez
12-
Dif
orm
ylhy
draz
ine
Dih
ydro
safr
olez
25-
Dim
etho
xy-4
-am
inos
tilbe
nez
33
-Dim
ethy
lben
zidi
ne2
HC
lz 1
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
a-E
cdys
one
Est
radi
olm
usta
rdy
N-E
thyl
-N-f
orm
ylhy
draz
ine
Eth
ylen
eim
ine
Eth
ylen
eox
idez
Eth
ylhy
draz
ine
HC
l5-
Flu
orou
raci
ly Fo
rmyl
hydr
azin
eG
lyci
dolz
c-1
23
45
6-H
exac
hlor
ocyc
lohe
xane
y H
exan
alm
ethy
lfor
myl
hydr
azon
eH
ydra
zine
z H
ydra
zine
sulf
atez
IQz
Isob
utyl
nitr
itez
Ison
iazi
dz Is
onic
otin
icac
idva
nilly
liden
ehyd
razi
de
Isop
rene
Lov
asta
tinM
eIQ
xz M
elph
alan
z 1-
Met
hyl-
14-
dihy
dro-
7-[ 2
-(5-
nitr
ofur
yl) v
inyl
] -4-
oxo-
18-
naph
thyr
idin
e-3-
carb
oxyl
ate
pota
ssiu
m
N-M
ethy
l-N
-for
myl
hydr
azin
eM
ethy
lmet
hane
sulf
onat
e3-
Met
hylb
utan
alm
ethy
lfor
myl
hydr
azon
eM
ethy
lene
chlo
ride
z M
ethy
lhyd
razi
ne
Met
hylh
ydra
zine
sulf
ate
( N-6
) -( M
ethy
lnit
roso
) ade
nine
(N
-6) -
( Met
hyln
itro
so) a
deno
sine
N-M
ethy
lola
cryl
amid
ey M
etro
nida
zole
z M
olyb
denu
mtr
ioxi
dey
Mon
oace
tylh
ydra
zine
Nap
htha
lene
15
-Nap
htha
lene
diam
inez
Nic
otin
icac
idhy
draz
ide
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez 3-
Nitr
o-3-
hexe
nez
Nit
robe
nzen
ez N
itrom
etha
nez
Nit
roso
dibu
tyla
min
ez N
-Nit
roso
dim
ethy
lam
inez
N-N
itros
ohex
amet
hyle
neim
ine
N-N
itro
sopi
peri
dine
z O
zone
y Pe
ntan
alm
ethy
lfor
myl
hydr
azon
en-
Pen
tylh
ydra
zine
HC
lPh
enes
teri
nz Ph
enyl
ethy
lhyd
razi
nesu
lfat
eP
roca
rbaz
ine
HC
lz N
-N-P
ropy
l-N
-for
myl
hydr
azin
eP
ropy
lhyd
razi
neH
Cl
Sel
eniu
msu
lde
z S
trep
tozo
toci
nz Su
lfal
late
z Te
lone
IIt
echn
ical
grad
ez 3
34
4-T
etra
amin
obip
heny
l4H
Clz
Tetr
anitr
omet
hane
z T-
2to
xin
Tri
chlo
roet
hyle
nez
Tri
ura
lint
echn
ical
grad
ey 2
45-
Tri
met
hyla
nilin
eH
Clz
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez U
reth
anez
Vin
ylch
lori
dez
Vin
ylu
orid
ez V
inyl
iden
ech
lori
dey
24-
Xyl
idin
eH
Cly
Mon
key
1U
reth
anez
Rat
551-
Ally
l-1-
nitr
osou
rea
2-A
min
o-5-
( 5-n
itro
-2-f
uryl
) -1
34-
oxad
iazo
le2
-Am
ino-
5-( 5
-nitr
o-2-
fury
l)-1
34
-thi
adia
zole
2-A
min
o-5-
nitr
othi
azol
ey 1-
Am
yl-1
-nitr
osou
rea
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
is-(
chlo
rom
ethy
l)et
herz
HC
blue
no1
z B
rom
oeth
anez
N-n
-But
yl-N
-nit
roso
urea
Cad
miu
mch
lori
deC
adm
ium
sulp
hate
( 11
) 1-
Chl
oroe
thyl
nitr
oso-
3-( 2
-hyd
roxy
prop
yl) u
rea
Chl
orop
rene
z C
obal
tsul
fate
hept
ahyd
rate
z 1
2-D
ibro
moe
than
ez D
imet
hylh
ydro
gen
phos
phit
ey tr
ans-
2-[(
Dim
ethy
lam
ino)
met
hylim
ino]
-5-
[ 2-(
5-ni
tro-
2-fu
ryl)
viny
l] -1
34-
oxad
iazo
le3
3-D
imet
hylb
enzi
dine
2H
Clz
12-
Epo
xybu
tane
y 1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
N-H
exyl
nitr
osou
rea
Hyd
razi
nez
Hyd
razi
nesu
lfat
ez 1-
( 2-H
ydro
xyet
hyl)
-1-n
itro
sour
eaz
Isob
utyl
nitr
itez
Ison
iazi
dz 4
4-M
ethy
lene
-bi
s(2-
chlo
roan
iline
) 4-
( Met
hyln
itros
amin
o)-1
-(3-
pyri
dyl)
-1-b
utan
ol4
-(M
ethy
lnit
rosa
min
o)-1
-(3-
pyri
dyl)
-1-(
buta
none
) N
-[ 3
-(5-
Nitr
o-2-
fury
l)-
12
4-ox
adia
zole
-5-y
l] -m
ethy
lace
tam
ide
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
3-N
itro-
3-he
xene
z 5-
Nitr
oace
naph
then
ez N
-Nit
roso
-bis
-(4
44-
tri
uoro
-N-b
utyl
) am
ine
N-N
itros
o-N
-met
hyl-
N-d
odec
ylam
ine
N-N
itros
o-N
-met
hyl-
N-t
etra
decy
lam
ine
N-N
itro
so-N
-met
hyld
ecyl
amin
eN
-Nitr
oso-
N-m
ethy
lure
az N
-Nitr
osob
is( 2
-hyd
roxy
prop
yl)
amin
eN
-Nitr
osob
is-2
3-d
ihyd
roxy
prop
ylam
ine
( 2-o
xopr
opyl
) am
ine
Nitr
osod
ibut
ylam
inez
N-N
itros
odim
ethy
lam
inez
N-N
itro
soep
hedr
ine
Nitr
osoe
thyl
met
hyla
min
eN
-Nit
roso
met
hyl
N-N
itro
som
ethy
l-( 3
-hyd
roxy
prop
yl) a
min
eN
itro
som
ethy
lund
ecyl
amin
eC
Ia
cid
red
114
Sod
ium
dich
rom
ate
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tetr
anit
rom
etha
nez
24
5-T
rim
ethy
lani
line
z 2
46-
Tri
met
hyla
nili
neH
Clz
Vin
ylch
lori
dez
Mam
mar
ygl
and
Dog
1Ly
nest
reno
lH
amst
er1
Vin
ylch
lori
dez
Mou
se24
5-A
zacy
tidin
ez B
enze
nez
CI
dir
ectb
lack
381
3-B
utad
iene
z C
alci
fero
lC
hlor
opre
nez
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
Die
thyl
stilb
estr
olz
a-E
cdys
one
Est
radi
olE
thyl
ene
oxid
ez F
uros
emid
ey G
lyci
dolz
Gri
seof
ulvi
nIs
onia
zidz
Ison
icot
inic
acid
vani
llylid
eneh
ydra
zide
( N
-6) -
( Met
hyln
itros
o)ad
enos
ine
Nitr
oben
zene
z R
eser
pine
z Su
lfal
late
z V
inyl
chlo
ride
z V
inyl
uor
idez
Vin
ylid
ene
chlo
ride
y
644
Rat
102
4-A
cety
lam
inob
iphe
nyl
2-A
cety
lam
ino
uore
nez
Acr
onyc
ine
Acr
ylam
ide
Acr
ylon
itri
leA
F-2
z 1-
Ally
l-1-
nitr
osou
rea
2-A
min
o-5-
( 5-n
itro-
2-fu
ryl)
-13
4-
oxad
iazo
le2
-Am
ino-
5-( 5
-nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
e2-
Am
ino-
5-ni
trot
hiaz
oley
4-A
min
odip
heny
lHC
l1-
Am
yl-1
-nit
roso
urea
Atr
azin
ey B
emit
radi
ne
Ben
zidi
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
4-B
is( 2
-hyd
roxy
ethy
l)am
ino-
2-( 5
-nit
ro-2
-thi
enyl
) qui
nazo
line
13-
But
adie
nez
N-n
-But
yl-N
-nitr
osou
rea
Cap
tafo
lz C
arbo
nte
trac
hlor
idez
Car
boxy
met
hyln
itros
oure
aC
hlor
ambu
cilz
Chl
orop
rene
z C
ytem
bena
y D
acar
bazi
nez
N-1
-Dia
ceta
mid
ouo
rene
46
-Dia
min
o-2-
( 5-n
itro-
2-fu
ryl)
-S-t
riaz
ine
24-
Dia
min
oani
sole
sulf
atez
24-
Dia
min
otol
uene
z 1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dib
rom
oman
nito
lz 1
3-D
ibut
yl-1
-nit
roso
urea
33
-Dic
hlor
oben
zidi
ne1
2-D
ichl
oroe
than
ez 3
3-D
imet
hoxy
benz
idin
e2H
Cl
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
12-
Dim
ethy
l-5-
nitr
oim
idaz
ole
tran
s-2-
[(D
imet
hyla
min
o)m
ethy
limin
o]-5
-[2-
( 5-n
itro
-2-f
uryl
) vin
yl] -
13
4-ox
adia
zole
Dim
ethy
lam
inoe
thyl
nitr
osoe
thyl
urea
nitr
ite
salt
33
-Dim
ethy
lben
zidi
ne2
HC
lz 2-
( 22
-Dim
ethy
lhyd
razi
no) -
4-( 5
-nitr
o-2-
fury
l)th
iazo
le
24-
Din
itro
tolu
ene
( con
tain
ing
10-
15
24-
Dio
xane
z 1-
Eth
ylni
tros
o-3-
( 2-h
ydro
xyet
hyl)
-ure
a1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
6-di
nitr
otol
uene
)zN
-(2-
Fluo
reny
l)-2
22
-tri
uo
roac
etam
ide
Form
icac
id2-
( 4-m
ethy
l-2-
thia
zoly
l)hy
draz
ide
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-
thia
zoly
l] hyd
razi
dez
Gly
cido
lz H
exam
ethy
lmel
amin
eN
-Hex
ylni
tros
oure
a2-
Hyd
razi
no-4
-(p-
amin
ophe
nyl)
thia
zole
z 2-
Hyd
razi
no-4
-( 5
-nit
ro-2
-fur
yl) t
hiaz
olez
2-H
ydra
zino
-4-(
p-ni
trop
heny
l)th
iazo
lez
Hyd
razo
benz
enez
1-( 2
-Hyd
roxy
ethy
l)-3
-[( 5
-nit
rofu
rfur
ylid
ene)
amin
o]-2
-im
idaz
olid
inon
e1-
( 2-H
ydro
xyet
hyl)
-nit
roso
-3-e
thyl
urea
1-(
2-H
ydro
xyet
hyl)
-1-n
itros
oure
az In
dom
etha
cin
IQz
IQH
Cl
Ison
iazi
dz 2-
Met
hoxy
-3-a
min
odib
enzo
fura
n4-
Met
hyl-
1-[(
5-ni
trof
urfu
rylid
ene)
amin
o]-2
-im
idaz
olid
inon
eN
-(N
-Met
hyl-
N-n
itro
soca
rbam
oyl)
-l-o
rnit
hine
3-M
ethy
lcho
lant
hren
e4
4-M
ethy
lene
-bi
s(2-
chlo
roan
iline
) 4
4-M
ethy
lene
-bis
( 2-m
ethy
lani
line)
Met
hyle
nech
lori
dez
Met
roni
dazo
lez
l-5-
Mor
phol
inom
ethy
l-3-
[(5-
nitr
ofur
fury
lide
ne) a
min
o]-
2-ox
azol
idin
one
HC
lN
ithia
zide
z 5-
Nitr
o-2-
fura
ldeh
yde
sem
icar
bazo
nez
3-( 5
-Nitr
o-2-
fury
l)-i
mid
azo(
12-
a)
pyri
dine
z 4-
( 5-N
itro-
2-fu
ryl)
thia
zole
N
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] ace
tam
ide
NN
-[6-
( 5-N
itro
-2-f
uryl
) -S-
tria
zine
-24
-diy
l] bis
acet
amid
e5-
Nitr
oace
naph
then
ez 1-
[(5-
Nit
rofu
rfur
ylid
ene)
amin
o]-2
-im
idaz
olid
inon
eN
itrom
etha
nez
1-N
itrop
yren
eN
orle
stri
nz O
chra
toxi
nA
z N
-(9-
Oxo
-2-
uore
nyl)
acet
amid
ePh
enac
etin
z Ph
enes
teri
nz Ph
IPH
Clz
Proc
arba
zine
HC
lz Pr
opan
esu
lton
e1
2-Pr
opyl
ene
oxid
ez St
yren
ey Su
lfal
late
z 4
4-S
ulfo
nylb
isac
etan
ilid
eTo
luen
edi
isoc
yana
te
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
o-T
olui
dine
HC
lz 1
23-
Tri
chlo
ropr
opan
ez 2
22-
Tri
uor
o-N
-[4-
( 5-n
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] ace
tam
idez
Trp
-P-2
acet
atez
Vin
ylch
lori
dez
FD
ampC
viol
etno
1y
Mes
ovar
ium
Rat
2Sa
lbut
amol
Ter
buta
line
Myo
card
ium
Mou
se2
Est
radi
olm
usta
rdy
Phen
este
rinz
Nas
alca
vity
bB
ush
baby
1N
-Nitr
osod
ieth
ylam
ine
Ham
ster
11A
ceta
ldeh
yde
Dia
llyln
itros
amin
eD
imet
hylc
arba
myl
chlo
ride
Hyd
razi
nez
Met
hyln
itro
sam
ino-
NN
-dim
ethy
leth
ylam
ine
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
N-N
itro
soal
lyl-
2-ox
opro
pyla
min
eN
-Nitr
osom
ethy
l-2
3-di
hydr
oxyp
ropy
lam
ine
N-N
itros
omor
phol
ine
N-N
itros
onor
nico
tine
N-N
itros
opip
erid
inez
Mou
se6
Ally
lgly
cidy
leth
ery
12-
Dib
rom
o-3-
chlo
ropr
opan
ez 1
2-D
ibro
moe
than
ez Fo
rmal
dehy
dez
N-N
itro
sohe
xam
ethy
lene
imin
e1
2-Pr
opyl
ene
oxid
ez
Rat
43A
ceta
ldeh
yde
Acr
ylon
itril
e1-
Azo
xypr
opan
eB
enze
nez
Bis
-(ch
loro
met
hyl)
ethe
rz p-
Cre
sidi
nez
Dia
llyln
itros
amin
e1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dim
ethy
lnitr
amin
eD
imet
hylv
inyl
chlo
ride
z D
initr
osoh
omop
iper
azin
e1
4-D
ioxa
nez
12-
Epo
xybu
tane
y Z
-Eth
yl-O
NN
-azo
xyet
hane
E
thyl
benz
ene
Eth
ylni
tros
ocya
nam
ide
Form
alde
hyde
z H
exam
ethy
lpho
spho
ram
ide
Hyd
razi
nez
N-N
itro
so-N
-met
hyld
ecyl
amin
edi
( N-N
itro
so) -
perh
ydro
pyri
mid
ine
N-N
itros
o(2
22-
tri
uoro
ethy
l)et
hyla
min
e1-
Nitr
oso-
34
5-tr
imet
hylp
iper
azin
eN
-Nitr
osoa
llyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nit
roso
ally
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itro
soal
lyle
than
olam
ine
N-N
itros
obis
( 2-h
ydro
xypr
opyl
) am
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
dipr
opyl
amin
eN
itros
oeth
ylm
ethy
lam
ine
N-N
itros
omet
hyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nitr
osom
ethy
l-( 2
-hyd
roxy
ethy
l)am
ine
N-N
itro
som
ethy
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itros
omet
hyl(
2-ox
opro
pyl)
amin
eN
-Nit
roso
norn
icot
ine-
1-N
-oxi
de
N-N
itro
sopi
peri
dine
z P
hena
cetin
z Ph
enyl
glyc
idyl
ethe
r1
2-Pr
opyl
ene
oxid
ez V
inyl
acet
atez
Vin
ylch
lori
dez
Ner
vous
Mou
se3
13-
But
adie
nez
N-N
itros
odim
ethy
lam
inez
Pro
carb
azin
eH
Clz
syst
emR
at21
Acr
ylam
ide
Acr
ylon
itril
eB
rom
oeth
anez
Chl
oram
buci
lz 1-
( 4-C
hlor
ophe
nyl)
-1-p
heny
l-2-
prop
ynyl
carb
amat
eC
yclo
phos
pham
idez
1-E
thyl
-1-n
itros
oure
aE
thyl
eneo
xide
z 1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
eaG
lu-P
-1z
Glu
-P-2
z G
lyci
dolz
R(
) -2-
Met
hyl-
N-n
itro
sopi
peri
dine
S(
) -2-
Met
hyl-
N-n
itro
sopi
peri
dine
M
ethy
lnit
ram
ine
N-N
itros
o-N
-met
hylu
reaz
N-N
itros
odie
than
olam
ine
1-P
heny
l-3
3-di
met
hyltr
iaze
neP
roca
rbaz
ine
HC
lz P
ropa
nesu
ltone
Vin
ylch
lori
dez
Ora
lcav
ityc
Ham
ster
4A
ceta
ldeh
yde
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
N-N
itros
omor
phol
ine
N-N
itro
sopi
peri
dine
z
Mou
se3
N-N
itros
ohex
amet
hyle
neim
ine
12
3-T
rich
loro
prop
anez
Vin
ylac
etat
ez
Rat
32A
cryl
amid
eA
cryl
onitr
ile
Ben
zene
z 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
CI
dir
ectb
lue
15C
Id
irec
tblu
e21
8z C
hlor
opre
nez
3-D
iazo
tyra
min
eH
Cl
12-
Dib
rom
o-3-
chlo
ropr
opan
ez 3
3-D
imet
hoxy
benz
idin
e2H
Cl
33
-Dim
ethy
lben
zidi
ne2
HC
lz D
imet
hylv
inyl
chlo
ride
z D
initr
osoh
omop
iper
azin
eG
lyci
dolz
IQz
MeA
-a-C
acet
atez
N-N
itros
o-2
3-di
hydr
oxyp
ropy
l-2-
hydr
oxyp
ropy
lam
ine
Nit
roso
-23
-dih
ydro
xypr
opyl
-2-
oxop
ropy
lam
ine
Nitr
oso-
N-m
ethy
l-N
-(2-
phen
yl) e
thyl
amin
eN
itro
soam
ylur
etha
nN
-Nitr
osod
ieth
ylam
ine
Nit
roso
ethy
lure
than
N
itros
ohep
tam
ethy
lene
imin
e1-
Nitr
osoh
ydan
toin
N-N
itros
omet
hyl(
2-ox
opro
pyl)
amin
eN
-Nit
roso
thia
ldin
eN
-Nitr
osot
hiom
orph
olin
eC
Ia
cid
red
114
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tolu
eney
12
3-T
rich
loro
prop
anez
Xyl
ene
mix
ture
( m-x
ylen
eo-
xyle
nep
-xyl
ene)
Ova
ryM
ouse
10B
enze
nez
13-
But
adie
nez
Die
thyl
stil
best
rolz
N-M
ethy
lola
cryl
amid
ey 5-
Nitr
o-2-
fura
ldeh
yde
sem
icar
bazo
nez
5-N
itroa
cena
phth
enez
1-[(
5-N
itro
furf
uryl
iden
e)am
ino]
hyda
ntoi
nz P
heno
lpht
hale
inz
Tam
oxif
enci
trat
ez 4-
Vin
ylcy
cloh
exen
ePa
ncre
asH
amst
er3
Nitr
oso-
23-
dihy
drox
ypro
pyl-
2-ox
opro
pyla
min
eN
itro
so-2
6-d
imet
hylm
orph
olin
eN
itro
so-2
-oxo
prop
ylet
hano
lam
ine
Mon
key
1U
reth
anez
Rat
222-
Am
ino-
5-ni
trop
heno
ly 1-
( Am
inom
ethy
l)cy
cloh
exan
eace
ticac
idA
zase
rine
But
ylbe
nzyl
phth
alat
ey C
hlor
endi
cac
idz
Cin
nam
ylan
thra
nila
tez
Clo
bra
tey
Dic
hlor
vosz
Eth
ylal
coho
ly H
ydro
chlo
ro
uoro
carb
on12
3IQ
HC
lM
alon
alde
hyde
sod
ium
saltz
MeA
-a-C
acet
atez
2-M
erca
ptob
enzo
thia
zole
y M
ethy
lclo
fena
pate
z N
-(N
-Met
hyl-
N-n
itros
ocar
bam
oyl)
-l-o
rnit
hine
4-(
Met
hyln
itro
sam
ino)
-1-(
3-py
ridy
l)-1
-but
anol
4-(
Met
hyln
itros
amin
o)-1
-( 3
-pyr
idyl
) -1-
( but
anon
e)N
afen
opin
Nitr
ofen
z To
luen
edi
isoc
yana
tec
omm
erci
algr
ade
( 24
( 80
) -an
d2
6( 2
0) -
)z1
23
-Tri
chlo
ropr
opan
ez
Peri
tone
alM
ouse
8B
is-1
2-(
chlo
rom
etho
xy) e
than
eB
is-1
4-(
chlo
rom
etho
xy) -
p-xy
lene
Bis
-(ch
loro
met
hyl)
ethe
rz C
hlor
opre
nez
tran
s-1
4-D
ichl
orob
uten
e-2
cavi
tyD
imet
hylc
arba
myl
chlo
ride
Phe
noxy
benz
amin
eH
Clz
Tri
s-1
23-
( chl
orom
etho
xy) p
ropa
neR
at22
Acr
onyc
ine
Acr
ylam
ide
Act
inom
ycin
DA
nili
neH
Cly
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
rom
ate
pota
ssiu
mz
Chl
oroz
otoc
in
Cyt
embe
nay
Dap
sone
y 1
2-D
ibro
moe
than
ez D
ibro
mom
anni
tolz
33
-Dim
ethy
lben
zidi
ne2
HC
lz 1
4-D
ioxa
nez
Eth
ylen
eox
idez
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Gly
cido
lz M
elph
alan
z N
-Met
hyl-
N4
-din
itros
oani
line
Mit
omyc
in-C
N-N
itro
so-2
24
-tri
met
hyl-
12-
dihy
droq
uino
line
poly
mer
Ph
enox
yben
zam
ine
HC
lz o-
Tolu
idin
eH
Clz
( Con
tinue
don
next
page
)
645
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Pitu
itar
ygl
and
Mou
se8
Die
thyl
stil
best
rolz
Eno
vid
Eth
ylen
eth
iour
eaz
Iodi
nate
dgl
ycer
olz
Isop
rene
Nor
lest
rinz
Pro
pylt
hiou
raci
lz Z
eara
leno
ney
Rat
73-
Am
inot
riaz
olez
12-
Dib
rom
oeth
anez
Die
thyl
stil
best
rolz
Eth
ylal
coho
ly 2-
Mer
capt
oben
zoth
iazo
ley
Met
roni
dazo
lez
Nor
lest
rinz
Pros
tate
Rat
4C
adm
ium
chlo
ride
N-N
itros
obis
( 2-h
ydro
xypr
opyl
) am
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
PhIP
HC
lz
Skin
Ham
ster
2U
reth
anez
Vin
ylch
lori
dez
Mou
se5
5-A
zacy
tidin
ez 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Chl
orop
rene
z G
lyci
dolz
Thi
o-te
paz
Rat
332-
Ace
tyla
min
ouo
rene
z 3-
Am
ino-
9-et
hylc
arba
zole
mix
ture
z 1-
Azo
xypr
opan
e2-
Azo
xypr
opan
eB
enze
nez
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
ol
tech
nica
lgra
dez
CI
dir
ectb
lue
15C
arbo
xym
ethy
lnitr
osou
rea
24-
Dia
min
oani
sole
sulf
atez
Dib
rom
odul
cito
lz D
ibro
mom
anni
tolz
Dim
etho
xane
2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 3
3-D
imet
hoxy
benz
idin
e-4
4-d
iisoc
yana
tey
33
-Dim
etho
xybe
nzid
ine
2HC
l3
3-D
imet
hylb
enzi
dine
2H
Clz
Dim
ethy
lvin
ylch
lori
dez
24-
Din
itro
tolu
ene
( con
tain
ing
10-
15
26-
dini
trot
olue
ne)z
1-E
thyl
nitr
oso-
3-( 2
-hyd
roxy
ethy
l)-u
rea
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Gly
cido
lz 1-
( 2-H
ydro
xyet
hyl)
-nit
roso
-3-e
thyl
urea
IQ
z L
asio
carp
ine
MeI
Qxz
N-(
N-M
ethy
l-N
-nitr
osoc
arba
moy
l)-l
-orn
ithi
ne
5-N
itro-
o-an
isid
inez
CI
aci
dre
d11
4p-
Ros
anili
neH
Clz
Thi
o-te
paz
Thi
oure
ay V
inyl
chlo
ride
z F
Damp
Cvi
olet
no1
y
Smal
lint
esti
neM
ouse
6C
apta
folz
Cap
tanz
N-E
thyl
-N-n
itro
-N-n
itro
sogu
anid
ine
Hyd
roge
npe
roxi
deN
-Met
hyl-
N-n
itro-
N-n
itros
ogua
nidi
nez
N-(
Tri
chlo
rom
ethy
lthi
o)ph
thal
imid
eM
onke
y1
Ure
than
ez
Rat
29A
cryl
onitr
ile
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
is( 2
3-d
ibro
mop
ropy
l)ph
osph
ate
mag
nesi
umsa
lt4
-Bis
( 2-h
ydro
xyet
hyl)
amin
o-2-
( 5-n
itro
-2-t
hien
yl) q
uina
zolin
eC
Id
irec
tblu
e15
Car
boxy
met
hyln
itros
oure
a1-
( 4-C
hlor
ophe
nyl)
-1-p
heny
l-2-
prop
ynyl
carb
amat
e2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 3
3-D
imet
hoxy
benz
idin
e2H
Cl
46-
Dim
ethy
l-2-
( 5-n
itro
-2-f
uryl
)py
rim
idin
etr
ans-
2-[(
Dim
ethy
lam
ino)
met
hylim
ino]
-5-[
2-( 5
-nit
ro-2
-fur
yl) v
inyl
] -1
34-
oxad
iazo
le3
3-D
imet
hylb
enzi
dine
2H
Clz
Z-E
thyl
-ON
N-a
zoxy
met
hane
1-E
thyl
-1-n
itros
oure
aFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z G
lu-P
-1z
Glu
-P-2
z IQ
z L
asio
carp
ine
N-M
ethy
l-N
-nitr
o-N
-nitr
osog
uani
dine
z N
-[5-
( 5-N
itro-
2-fu
ryl)
-13
4-t
hiad
iazo
l-2-
yl] a
ceta
mid
ez N
-Nitr
oso-
N-i
sobu
tylu
rea
3-N
itro
so-2
-oxa
zoli
dino
neN
itro
soet
hylu
reth
ane
PhI
PH
Clz
Pro
pane
sulto
neQ
uerc
etin
y C
Ia
cid
red
114
Trp
-P-2
acet
atez
Sple
enR
at7
Ani
line
HC
ly A
zobe
nzen
ey p-
Chl
oroa
nili
neH
Clz
Dap
sone
y o-
Nitr
osot
olue
neD
ampC
red
no9
y o-
Tolu
idin
eH
Clz
Stom
ach
Ham
ster
18A
F-2z
14-
Din
itros
o-2
6-di
met
hylp
iper
azin
eFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z H
ydra
zine
z N
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
N-[
4-( 5
-Nitr
o-2-
fury
l)-2
-thi
azol
yl] a
ceta
mid
eN
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] for
mam
idez
N-N
itro
so-2
3-d
ihyd
roxy
prop
yl-2
-hyd
roxy
prop
ylam
ine
Nitr
oso-
23-
dihy
drox
ypro
pyl-
2-ox
opro
pyla
min
eN
-Nitr
oso-
ethy
l-2-
oxop
ropy
lure
aN
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aN
itros
o-5-
met
hylo
xazo
lidon
eN
-Nit
roso
-N-m
ethy
lure
than
N-N
itros
o-1
3-ox
azol
idin
eN
-Nit
roso
-2-p
heny
leth
ylur
ea1
-Nit
roso
-34
5-t
rim
ethy
lpip
eraz
ine
Ure
than
ez V
inyl
chlo
ride
z
Mou
se63
Ace
tald
ehyd
em
ethy
lfor
myl
hydr
azon
eA
ciu
orfe
nA
F-2
z 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 2-
Am
ino-
4-( 5
-nitr
o-2-
fury
l)th
iazo
lez
tran
s-5-
Am
ino-
3[2-
( 5-n
itro-
2-fu
ryl)
viny
l] -1
24-
oxad
iazo
leA
reco
line
HC
lB
enza
ldeh
ydey
Ben
zofu
ranz
Ben
zotr
ichl
orid
eB
enzy
lace
tate
y B
enzy
lchl
orid
ey B
rom
oeth
anol
13
-But
adie
nez
But
ylat
edhy
drox
yani
sole
z 1
1-di
-N-B
utyl
hydr
azin
eC
affe
icac
idz
Cap
tafo
lz C
arba
zole
Cat
echo
lz 3-
Chl
oro-
2-m
ethy
lpro
pene
tec
hnic
algr
ade
( con
tain
ing
5di
met
hylv
inyl
chlo
ride
)z3
-(C
hlor
omet
hyl)
pyri
dine
HC
lz C
hlor
opre
nez
2-C
hlor
opro
pana
l1-
Chl
orop
rope
neC
ypro
tero
neac
etat
e1
1-D
ially
lhyd
razi
ne1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dic
hlor
vosz
Dig
lyci
dylr
esor
cino
leth
ert
echn
ical
grad
ez D
imet
hylv
inyl
chlo
ride
z D
init
roso
pipe
razi
neE
stra
diol
mus
tard
y E
thyl
acry
late
z Fo
rmic
acid
2-[ 4
-( 5
-nit
ro-2
-fur
yl) -
2-th
iazo
lyl] h
ydra
zide
z G
lyci
dolz
2-H
ydra
zino
-4-(
5-ni
tro-
2-fu
ryl)
thia
zole
z N
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
ICI
1628
46z
IQz
Isop
rene
Lov
asta
tin
MeI
Q1
-Met
hyl-
14-
dihy
dro-
7-[ 2
-(5-
nitr
ofur
yl) v
inyl
] -4-
oxo-
18-
naph
thyr
idin
e-3-
carb
oxyl
ate
pota
ssiu
m3
-(5-
Nitr
o-2-
fury
l)-
imid
azo(
12-
a) p
yrid
inez
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
N-[
4-( 5
-Nitr
o-2-
fury
l)-2
-thi
azol
yl] f
orm
amid
ez N
-Nit
roso
-N
-met
hylu
reaz
Nit
roso
dibu
tyla
min
ez N
-Nit
roso
hexa
met
hyle
neim
ine
N-N
itros
opip
erid
inez
b-P
ropi
olac
tone
z Se
sam
olz
Sty
rene
oxid
ez Te
lone
IIt
echn
ical
grad
ez N
-(T
rich
loro
met
hylth
io) p
htha
limid
e1
23-
Tri
chlo
ropr
opan
ez 2
22-
Tri
uo
ro-N
-[4-
( 5-n
itro
-2-f
uryl
) -2-
thia
zoly
l]ac
etam
idez
Tri
ur
alin
tec
hnic
algr
adey
Tri
s(2-
chlo
roet
hyl)
phos
phat
ez T
ris(
23-
dibr
omop
ropy
l)ph
osph
atez
Vin
ylac
etat
ez
Rat
85A
ceto
ne[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zone
1-A
ceto
xysa
frol
ey A
cryl
onitr
ile
1-A
llyl
-1-n
itro
sour
ea2
-Am
ino-
5-( 5
-nit
ro-2
-fur
yl) -
13
4-ox
adia
zole
2-
Am
ino-
5-( 5
-nitr
o-2-
fury
l)-1
34
-thi
adia
zole
2-A
min
o-4-
( 5-n
itro
-2-f
uryl
) thi
azol
ez 1-
Am
yl-1
-nit
roso
urea
Ari
stol
ochi
cac
id
sodi
umsa
lt( 7
7A
AI
21
AA
II)
Ben
zene
z B
enzo
( a) p
yren
ez 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bis
( 23
-dib
rom
opro
pyl)
phos
phat
em
agne
sium
salt
BL
-634
1H
Cl
N-n
-But
yl-N
-nitr
osou
rea
But
ylat
edhy
drox
yani
sole
z b
-But
yrol
acto
neC
affe
icac
idz
Cat
echo
lz 3-
Chl
oro-
2-m
ethy
lpro
pene
tec
hnic
algr
ade
( con
tain
ing
5di
met
hylv
inyl
chlo
ride
)z4
-Chl
oro-
o-ph
enyl
ened
iam
inez
Chl
oro
uoro
met
hane
3-
( Chl
orom
ethy
l)py
ridi
neH
Clz
Cip
rob
rate
z C
upfe
rron
z 1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
Dig
lyci
dylr
esor
cino
leth
ert
echn
ical
grad
ez 2
5-D
imet
hoxy
-4-a
min
osti
lben
ez D
imet
hylh
ydro
gen
phos
phit
ey 4
6-D
imet
hyl-
2-( 5
-nit
ro-2
-fu
ryl)
pyri
mid
ine
tran
s-2-
[(D
imet
hyla
min
o)m
ethy
limin
o]-5
-[2-
( 5-n
itro
-2-f
uryl
) vin
yl] -
13
4-ox
adia
zole
Dim
ethy
lvin
ylch
lori
dez
Epi
chlo
rohy
drin
y E
thyl
acry
late
z E
thyl
ene
oxid
ez 2-
Flu
oroe
thyl
-nitr
osou
rea
Gly
cido
lz N
-Hex
ylni
tros
oure
a1-
Hyd
roxy
anth
raqu
inon
e1-
( 2-H
ydro
xyet
hyl)
-1-
nitr
osou
reaz
1-( 3
-Hyd
roxy
prop
yl) -
1-ni
tros
oure
a1
-Hyd
roxy
safr
olez
ICI
1628
46z
Lox
tidin
eL
upit
idin
e3H
Cl
Mer
curi
cch
lori
dey
3-M
etho
xyca
tech
ol4
-Met
hoxy
phen
olN
-Met
hyl-
N-n
itro-
N-n
itros
ogua
nidi
nez
N-M
ethy
l-N
-nit
roso
benz
amid
e4-
Met
hylc
atec
hol
Met
hyln
itro
socy
anam
ide
3-( 5
-Nit
ro-2
-fur
yl) -
imid
azo(
12-
a) p
yrid
inez
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
4-( 5
-Nit
ro-2
-fur
yl) t
hiaz
ole
2-N
itro
uo
rene
8-N
itro
quin
olin
eN
itro
so-B
aygo
nN
-Nit
roso
-23
-dih
ydro
xypr
opyl
-2-h
ydro
xypr
opyl
amin
eN
itros
o-2
3-di
hydr
oxyp
ropy
l-2-
oxop
ropy
lam
ine
1-N
itro
so-3
5-d
imet
hyl-
4-be
nzoy
lpip
eraz
ine
N-N
itro
so-N
-met
hyl-
N-d
odec
ylam
ine
Nitr
oso-
N-m
ethy
l-N
-(2-
phen
yl) e
thyl
amin
eN
-Nit
roso
-N-m
ethy
ldec
ylam
ine
N-N
itro
so-N
-met
hylu
reaz
Nit
roso
-12
36
-tet
rahy
drop
yrid
ine
N-N
itro
sobe
nzth
iazu
ron
Nitr
osod
ibut
ylam
inez
N-N
itros
odie
thyl
amin
eN
-Nit
roso
ephe
drin
eN
itros
oeth
ylur
etha
nO
mep
razo
ley
Phen
acet
inz
Piv
alol
acto
ney
b-P
ropi
olac
tone
z N
-Pro
pyl-
N-n
itro
-N-n
itro
sogu
anid
ine
12-
Pro
pyle
neox
idez
Ses
amol
z St
yren
eox
idez
Sulf
alla
tez
Telo
neII
tec
hnic
algr
adez
12
3-T
rich
loro
prop
anez
24
6-T
rim
ethy
lani
line
HC
lz
646
Subc
utan
eous
Mou
se4
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 1
2-D
ibro
moe
than
ez N
2-c
-Glu
tam
yl-p
-hyd
razi
nobe
nzoi
cac
idG
lyci
dolz
tissu
eR
at13
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 2
4-D
iam
inot
olue
ne2
HC
lz 1
2-D
ichl
oroe
than
ez D
imet
hoxa
ne1
4-D
ioxa
nez
MeA
-a-C
acet
atez
44
-Met
hyle
ne-b
is( 2
-met
hyla
nili
ne)
o-N
itro
soto
luen
ep-
Ros
anili
neH
Clz
Tolu
ene
diis
ocya
nate
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
o-T
olui
dine
HC
lz 2
45-
Tri
met
hyla
nilin
eH
Clz
25-
Xyl
idin
eH
Clz
Test
isM
ouse
4D
ieth
ylst
ilbe
stro
lz Fi
nast
erid
eR
eser
pine
z Ta
mox
ifen
citr
atez
Rat
185-
Aza
cytid
inez
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 1
3-B
utad
iene
z N
-But
yl-N
-(4-
hydr
oxyb
utyl
) nitr
osam
ine
Cad
miu
mch
lori
de
2-C
hlor
o-1
11-
tri
uoro
etha
ne1
1-D
ichl
oro-
1-u
oroe
than
eH
ydro
chlo
rou
oroc
arbo
n12
3M
ethy
lter
t-bu
tyle
ther
z M
ethy
lclo
fena
pate
z M
etro
nida
zole
z N
-Nit
roso
dim
ethy
lam
inez
Oxo
linic
acid
y SD
Z20
0-11
01
11
2-Te
tra
uoro
etha
ney
Tri
chlo
roet
hyle
nez
Tri
nitr
ogly
ceri
nV
inyl
chlo
ride
z
Thy
roid
glan
dH
amst
er4
Hex
achl
orob
enze
nez
Hyd
razi
nez
Met
hylt
hiou
raci
lU
reth
anez
Mou
se18
3-A
min
o-4-
etho
xyac
etan
ilide
y H
Cbl
ueno
1z
tert
-But
ylal
coho
lz C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
24
-Dia
min
oani
sole
sulf
atez
Die
thyl
stil
best
rolz
Dox
ylam
ine
succ
inat
ez E
thio
nam
idey
Eth
ylen
eth
iour
eaz
44
-Met
hyle
nedi
anil
ine
2HC
lz 1
5-N
apht
hale
nedi
amin
ez N
itrob
enze
nez
Oxa
zepa
my
44
-Oxy
dian
iline
z C
Ip
igm
entr
ed3z
Sulf
amet
hazi
ne2
37
8-T
etra
chlo
rodi
benz
o-p-
diox
inz
44
-Thi
odia
nilin
ez
Rat
33A
cryl
amid
e3-
Am
inot
riaz
olez
o-A
nisi
dine
HC
lz B
emit
radi
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bro
mat
epo
tass
ium
z C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
Chl
orop
rene
z 2
4-D
iam
inoa
niso
lesu
lfat
ez N
N-D
ieth
ylth
iour
eay
1-E
thyl
-1-n
itro
sour
ea
Eth
ylen
eth
iour
eaz
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Flu
vast
atin
Gly
cido
lz Io
dina
ted
glyc
erol
z Is
obut
eney
Mal
onal
dehy
des
odiu
msa
ltz
Met
him
azol
e4
4-M
ethy
lene
bis(
NN
-dim
ethy
l)be
nzen
amin
ez 4
4-M
ethy
lene
dian
iline
2H
Clz
Mir
exp
hoto
-N
itro
benz
enez
N-N
itro
sobi
s(2-
oxop
ropy
l)am
ine
44
-Oxy
dian
iline
z Pr
opyl
thio
urac
ilz p-
Ros
anil
ine
HC
lz 2
37
8-Te
trac
hlor
odib
enzo
-p-d
ioxi
nz 4
4-T
hiod
iani
linez
Thi
oura
cilz
Tri
met
hylt
hiou
reay
Vin
ylac
etat
ez Z
inc
dim
ethy
ldith
ioca
rbam
atez
Uri
nary
blad
der
Dog
23
3-D
ichl
orob
enzi
dine
44
-Met
hyle
ne-b
is( 2
-chl
oroa
nilin
e)H
amst
er3
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-t
hiaz
olyl
] hyd
razi
dez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
acet
amid
eN
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] for
mam
idez
Mou
se12
2-A
cety
lam
ino
uore
nez
4-A
min
odip
heny
l2-
Am
inod
iphe
nyle
neox
ide
o-A
nisi
dine
HC
lz 4-
Chl
oro-
4-a
min
odip
heny
leth
erz
p-C
resi
dine
z 4-
Eth
ylsu
lpho
nyln
apht
hale
ne-1
-sul
fona
mid
eN
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez P
hena
cetin
z Te
lone
IIt
echn
ical
grad
ez U
raci
lz
Mon
key
12-
Nap
hthy
lam
inez
Rat
49A
ceta
min
ophe
nz A
llyli
soth
iocy
anat
ey 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 2-
Am
ino-
4-( 5
-nitr
o-2-
fury
l)th
iazo
lez
4-A
min
o-2-
nitr
ophe
noly
11-A
min
ound
ecan
oic
acid
y o-
Ani
sidi
neH
Clz
Ari
stol
ochi
cac
ids
odiu
msa
lt( 7
7A
AI
21
AA
II)
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez C
Id
ispe
rse
blue
1y N
-But
yl-N
-(4-
hydr
oxyb
utyl
) nitr
osam
ine
4-C
hlor
o-o-
phen
ylen
edia
min
ez m
-Cre
sidi
ney
p-C
resi
dine
z C
yclo
phos
pham
idez
Die
thyl
ene
glyc
olD
imet
hyla
rsin
icac
idy
Fose
tylA
lIQ
HC
lM
eA-a
-Cac
etat
ez M
elam
iney
2-M
etho
xy-3
-am
inod
iben
zofu
ran
2-N
apht
hyla
min
ez N
itril
otri
acet
icac
idz
Nitr
ilot
riac
etic
acid
tri
sodi
umsa
ltm
onoh
ydra
tey
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez o-
Nitr
oani
sole
z N
-Nitr
oso-
N-m
ethy
l-N
-dod
ecyl
amin
eN
-Nitr
oso-
N-m
ethy
l-N
-tet
rade
cyla
min
eN
-Nit
roso
-N-m
ethy
ldec
ylam
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
Nitr
osod
ibut
ylam
inez
N-N
itro
sodi
phen
ylam
iney
o-N
itros
otol
uene
N-O
xydi
ethy
lene
thio
carb
amyl
-N-o
xydi
ethy
lene
sulf
enam
ide
Phe
nace
tinz
Phen
azon
eo-
Phen
ylph
enat
eso
dium
y o-
Phen
ylph
enol
y P
otas
sium
bica
rbon
ate
Purp
urin
Que
rcet
iny
p-Q
uino
nedi
oxim
ey Sa
ccha
rin
sodi
umy
Sali
cyla
zosu
lfap
yrid
inez
o-To
luen
esul
fona
mid
eo-
Tolu
idin
eH
Clz
Trp
-P-2
acet
atez
Ura
cilz
Ute
rus
Ham
ster
1N
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aM
ouse
12B
rom
oeth
anez
Chl
oroe
than
ey D
acar
bazi
nez
12-
Dic
hlor
oeth
anez
Die
thyl
stil
best
rolz
Eth
ylen
eox
idez
Gly
cido
lz ( N
-6) -
( Met
hyln
itros
o)ad
enos
ine
Proc
arba
zine
HC
lz 1
23-
Tri
chlo
ropr
opan
ez T
rim
ethy
lpho
spha
tey
Vin
ylac
etat
ez
Rat
26A
cryl
amid
e1-
Ally
l-1-
nitr
osou
rea
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
1-A
myl
-1-n
itros
oure
aA
traz
iney
CI
dir
ectb
lue
15B
rom
ocri
ptin
em
esyl
atey
N-n
-But
yl-N
-nit
roso
urea
Cal
cium
valp
roat
eC
apta
nz 2-
Chl
oro-
11
1-tr
iuo
roet
hane
Dac
arba
zine
z D
amin
ozid
ez 3
3-D
imet
hoxy
benz
idin
e-4
4-d
iisoc
yana
tey
33
-Dim
etho
xybe
nzid
ine
2HC
lD
imet
hyla
min
oeth
ylni
tros
oeth
ylur
ean
itri
tesa
lt1-
Eth
ylni
tros
o-3-
( 2-h
ydro
xyet
hyl)
-ure
a1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
N-H
exyl
nitr
osou
rea
ICR
F-1
59z
Isop
hosp
ham
idez
15-
Nap
htha
lene
diam
inez
Nit
robe
nzen
ez N
orle
stri
nz 4
4-T
hiod
iani
linez
Vin
ylac
etat
ez
Vag
ina
Mou
se1
AZ
Tz
Rat
2A
ZT
z N
-n-B
utyl
-N-n
itro
sour
ea( C
ontin
ued
onne
xtpa
ge)
647
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Vas
cula
rsy
stem
Ham
ster
91
2-D
imet
hylh
ydra
zine
2H
Cl
Gly
cido
lz H
exac
hlor
oben
zene
z N
-Nit
roso
-eth
yl-2
-oxo
prop
ylur
eaN
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aN
-Nitr
oso-
oxop
ropy
lchl
oroe
thyl
urea
N-N
itro
so-o
xopr
opyl
urea
N-N
itros
o-2-
phen
ylet
hylu
rea
Vin
ylch
lori
dez
Mou
se59
A-a
-CN
-Ace
tyl-
4-( h
ydro
xym
ethy
l)ph
enyl
hydr
azin
e1-
Ace
tyl-
2-ph
enyl
hydr
azin
eA
llyl
hydr
azin
eH
Cl
Are
colin
eH
Cl
Aza
thio
prin
eB
enzi
dine
2H
Cl
2-B
iphe
nyla
min
eH
Cly
13-
But
adie
nez
Cap
tafo
lz C
arba
myl
hydr
azin
eH
Cl
4-C
hlor
o-4
-am
inod
iphe
nyle
ther
z 1-
Chl
oro-
4-ni
trob
enze
ney
5-C
hlor
o-o-
tolu
idin
ey 4-
Chl
oro-
o-to
luid
ine
HC
ly p-
Chl
oroa
nilin
eH
Clz
Chl
orop
rene
z C
upfe
rron
z D
acar
bazi
nez
Dam
inoz
idez
24-
Dia
min
otol
uene
2H
Clz
12-
Dib
rom
oeth
anez
Dif
talo
ne7
12-
Dim
ethy
lben
z(a)
anth
race
ne1
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
N-E
thyl
-N-f
orm
ylhy
draz
ine
Eth
ylhy
draz
ine
HC
lG
lu-P
-1z
Glu
-P-2
z p-
Hyd
razi
nobe
nzoi
cac
idH
Cl
1-H
ydro
xysa
frol
ez Is
opre
neM
eA-a
-Cac
etat
ez N
-Met
hyl-
N-f
orm
ylhy
draz
ine
2-M
ethy
l-1-
nitr
oant
hraq
uino
nez
Mic
hler
rsquoske
tone
z 5-
Nitr
o-o-
tolu
idin
ey N
itro
fenz
N-N
itros
o-N
-met
hylu
reaz
Pent
achl
oroa
niso
lez
23
45
6-Pe
ntac
hlor
ophe
nol(
Dow
icid
eE
C-7
)y2
34
56
-Pen
tach
loro
phen
olt
echn
ical
grad
ez n-
Pen
tylh
ydra
zine
HC
lPh
enyl
ethy
lhyd
razi
nesu
lfat
ePh
enyl
hydr
azin
eH
Cl
Ster
igm
atoc
ysti
nz Te
tra
uoro
ethy
lene
z To
luen
edi
isoc
yana
tec
omm
erci
algr
ade
( 24
( 80
) -an
d2
6( 2
0) -
)zo
-Tol
uidi
neH
Clz
24
6-T
rich
loro
anil
iney
24
5-T
rim
ethy
lani
line
HC
lz 2
46-
Tri
met
hyla
nili
neH
Clz
Ure
than
ez V
inyl
carb
amat
eV
inyl
chlo
ride
z V
inyl
uor
idez
Vin
ylid
ene
chlo
ride
y 2
5-X
ylid
ine
HC
lz
Mon
key
2A
ato
xin
B1y
Ure
than
ez
Rat
32A
nilin
eH
Cly
Azo
benz
eney
Ben
zene
z C
livor
ine
Cup
ferr
onz
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
Z-E
thyl
-ON
N-a
zoxy
etha
neZ
-Eth
yl-O
NN
-azo
xym
etha
neI
QH
Cl
Las
ioca
rpin
e4
4-M
ethy
lene
-bis
( 2-c
hlor
oani
line)
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
N-N
itros
o-( 2
-hyd
roxy
prop
yl) -
( 2-h
ydro
xyet
hyl)
amin
eN
itro
so-1
23
6-t
etra
hydr
opyr
idin
eN
-Nitr
osob
is( 2
-oxo
prop
yl) a
min
eN
-Nit
roso
diet
hano
lam
ine
N-N
itro
sodi
ethy
lam
ine
N-N
itros
odim
ethy
lam
inez
N-N
itros
omet
hyl-
( 2-t
osyl
oxye
thyl
) am
ine
N-N
itros
omor
phol
ine
N-N
itro
sopy
rrol
idin
ez Pe
tasi
teni
neS
teri
gmat
ocys
tinz
Sym
phyt
ine
Tetr
auo
roet
hyle
nez
o-To
luid
ine
HC
lz T
rp-P
-2ac
etat
ez V
inyl
brom
ide
Vin
ylch
lori
dez
Vin
yl
uori
dez
aT
here
was
nore
port
edta
rget
site
in1
spec
ies
( rat
sor
mic
e)fo
r5
chem
ical
sw
ithsu
pers
crip
tsb
utth
ech
emic
alw
asev
alua
ted
byth
epu
blis
hed
auth
oras
aca
rcin
ogen
ald
rinz
diel
drin
z N
-nit
roso
pyrr
olid
inez
23
45
6-pe
ntac
hlor
ophe
nol
( Dow
icid
eE
C-7
)ya
ndur
etha
nez
bN
asal
cavi
tyin
clud
estis
sues
ofth
eno
sen
asal
turb
inat
esp
aran
asal
sinu
ses
and
trac
hea
c Ora
lcav
ityin
clud
estis
sues
ofth
em
outh
oro
phar
ynx
phar
ynx
and
lary
nx
Ach
emic
alis
liste
dun
der
each
orga
nev
alua
ted
aspo
sitiv
ein
anex
peri
men
tin
that
spec
ies
byat
leas
t1au
thor
The
refo
rea
chem
ical
may
beli
sted
unde
rse
vera
ltar
geto
rgan
san
dev
ery
chem
ical
liste
din
the
tabl
eis
posi
tive
inat
leas
t1sp
ecie
sIn
orde
rto
com
pare
resu
ltsin
rats
and
mic
esy
mbo
lsfo
llow
chem
ical
ste
sted
inbo
thsp
ecie
sa
zin
dica
tes
that
the
chem
ical
ispo
sitiv
eat
som
esi
tein
both
spec
ies
and
ay
indi
cate
sth
atit
was
test
edin
both
butp
ositi
vein
only
1a
Nth
enu
mbe
rof
chem
ical
sw
ithat
leas
t1po
sitiv
ete
stat
that
site
inth
atsp
ecie
sB
ecau
sem
any
chem
ical
sin
duce
tum
ors
atm
ore
than
1si
tein
agi
ven
spec
ies
man
ych
emic
als
appe
arm
ore
than
once
inth
eta
ble
648
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649
species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters
RESULTS IN RATS AND MICE
For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens
TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database
Chemicals evaluated as carcinogenic in
Rats Mice
All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)
Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2
a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not
b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats
All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical
to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included
The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site
Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common
650 GOLD ET AL TOXICOLOGIC PATHOLOGY
TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)
Target site Agent mixture or industrial process
Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e
Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke
Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products
Brain Vinyl chloride a
Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e
Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena
Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system
Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as
a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell
lymphotropic virus type I (HTLV-I) Vinyl chloridea
Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production
Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)
Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea
Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea
Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)
Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea
Mesenchymal tumors Azathioprinea
Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust
Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust
Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid
(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke
Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production
8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots
Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e
Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays
IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD
IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no
tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance
is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651
sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites
Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to
be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)
Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)
Target Organs of Human CarcinogensTo complement the compendium of target organs in car-
cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke
In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)
Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens
Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from
bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)
ACKNOWLEDGMENTS
We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention
REFERENCES
1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56
2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600
3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998
4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685
5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404
6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605
7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246
8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100
9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash
23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC
11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the
652 GOLD ET AL TOXICOLOGIC PATHOLOGY
US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240
12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute
13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program
14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX
15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11
16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash
34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c
Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729
640 GOLD ET AL TOXICOLOGIC PATHOLOGY
results included in the compendium (Table 1) The CPDBincludes 1381 papers published in the general literaturethrough 1996 and 430 Technical Reports of the NationalCancer InstituteNational Toxicology Program (NCINTP)published through 1998 Results are reported for 6073 ex-periments on 1458 chemicals of which 738 induce tumorsin 1 or more experiments
A word of caution is necessary about the limitations ofthe CPDB Only long-term experiments meeting a set of cri-teria designed to measure tumorigenic dose-rate (TD50) areincluded therefore the CPDB does not cover all cancer testsAdditionally for the identi cation of target sites for the com-pendium we do not personally evaluate whether a compoundinduced tumors at a given site rather the opinion of the pub-lished author is used For published opinions that are notclear even after personal communication with the publishedauthor the site is not considered a target and is not reportedin the compendium
Results of all NCINTP Technical Reports are included inthe CPDB except a few for which no whole body exposure inmgkgday could be calculated because the test agent was aparticulate or the route of administration was dermal (12 13)[httpntp-serverniehsnihgov] In the compendium a siteis classi ed as a target in an NCINTP bioassay if the eval-uation in the Technical Report was ldquocarcinogenicrdquo ldquoclearrdquoor ldquosomerdquo evidence of carcinogenic activity Sites that wereevaluated as ldquoequivocalrdquo are not included (9)
In the general literature experimental designs as well asthe authorsrsquo choice of information to report are quite diverseand bioassays have been included only if they meet all of thefollowing conditions
1 Animals on test were mammals2 Administration was begun early in life (100 days of age
or less for rats mice and hamsters)3 Route of administration was diet water gavage inhala-
tion intravenous or intraperitoneal injection (ie wherethe whole body was more likely to have been exposedrather than only a speci c site as with subcutaneous in-jection or skin painting)
4 Test agent was administered alone rather than in combi-nation with other chemicals
5 Exposure was chronic with not more than 7 days betweenadministrations
6 Duration of exposure was at least one fourth the standardlife span for that species For rodents the standard lifespan is 2 years
7 Duration of experiment was at least half the standard lifespan for that species
8 Research design included a concurrent control group9 Research design included at least 5 animals per group
10 Surgical intervention was not performed11 Pathology data were reported for the number of animals
with tumors rather than the total number of tumors12 Results reported were original data rather than sec-
ondary analyses of experiments already reported by otherauthors
More details on inclusion criteria can be found in Goldand coworkers (6) and httppotencyberkeleyedutextmethodshtml
Because we have adhered strictly to the standard inclu-sion criteria bioassays of particulate or brous matters arenot in the compendium eg asbestos cigarette smoke anddusts There are no studies using a single administration ofthe test agent no experiments by skin painting subcutaneousinjection or in utero exposure and no cocarcinogenesis ex-periments For a series of NCI long-term studies in monkeyssome of the inclusion rules have been relaxed details arereported in Appendix 1 of Gold et al 1999 (2)
There is great diversity in results for different chemicalsin the CPDB eg in the number of times a chemical has beentested among the 1148 chemicals tested in rats 25 haveonly 1 test in the CPDB and 50 have 2 tests however25 chemicals have 10 or more tests For the 938 chemicalstested in mice the parallel numbers are 11 with 1 test 57with 2 tests and 15 chemicals with more than 10 tests Ofthe 738 carcinogens reported here 54 (397738) have beentested in more than 1 species In the compendium (Table 1)a target site is identi ed by a positive result in any one ex-periment in the species thus different target sites may beidenti ed from the same or different experiments Chemi-cals that are tested more often have a greater chance of nd-ing multiple target sites Results on chemicals that have notbeen evaluated as carcinogenic are ignored in the target or-gan compendium (Table 1) however detailed results of thoseexperiments are reported in the plot of the CPDB (2 3 6)httppotencyberkeleyedu
Guide to the Compendium of Target Organs for 738Carcinogens
Table 1 reports results on 738 chemicals in the CPDB thatinduce tumors in at least 1 of 35 target organs in rats micehamsters monkeys or dogs The table is organized alpha-betically by target site and within each site by species andchemical Our previously unpublished analyses of experi-mental results that will be published in a forthcoming plot ofthe CPDB are included (3)
To facilitate use of the compendium the features aredescribed below using the example of adrenal gland whichis the rst of 35 target sites in Table 1 Under adrenal gland1 chemical is listed in hamsters 8 in mice and 16 in ratsIf a chemical name is followed by a superscript (either yor z) this indicates that the CPDB includes test results inboth rats and mice for example under adrenal gland in rats2-mercaptobenzothiazole but not isomazole has a super-script Because isomazole has no superscript it only hastests in the CPDB in the species reported in this case ratsThe superscript y for 2-mercaptobenzothiazole indicatesthat the chemical has been tested in both rats and mice butinduced tumors only in the reported species in this case ratsThe superscript z for 12-dibromo-3-chloropropane (DBCP)indicates that DBCP is carcinogenic at some target site inboth rats and mice Although the superscript z does not indi-cate whether DBCP induced tumors at the same target site inboth rats and mice this can easily be determined by lookingat mice under adrenal gland for the chemical name DBCPBecause it is not there DBCP induced tumors in mice only atsites other than the adrenal gland In contrastpentachloroanisole z induced adrenal tumors in both speciesbeacuse it is listed under that site for both species Bycomparing the chemicals with superscripts listed under each
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Adr
enal
glan
dH
amst
er1
Ure
than
ez
Mou
se8
Car
bon
tetr
achl
orid
ez F
uran
z 4
4-M
ethy
lene
dian
iline
2H
Clz
Pen
tach
loro
anis
olez
23
45
6-Pe
ntac
hlor
ophe
nol(
Dow
icid
eE
C-7
)y
23
45
6-P
enta
chlo
roph
enol
tec
hnic
algr
adez
p-R
osan
ilin
eH
Clz
11
2-T
rich
loro
etha
ney
Rat
16B
rom
oeth
anez
4-C
hlor
o-m
-phe
nyle
nedi
amin
ez C
obal
tsul
fate
hept
ahyd
rate
z 1
2-D
ibro
mo-
3-ch
loro
prop
anez
Die
thyl
stilb
estr
olz
Eth
ylal
coho
ly In
dolid
anI
som
azol
e2-
Mer
capt
oben
zoth
iazo
ley
Mir
exz
Pen
tach
loro
anis
olez
Phe
nolp
htha
lein
z 1
2-Pr
opyl
ene
oxid
ez C
Ip
igm
entr
ed3z
Res
erpi
nez
Ret
inol
acet
ate
Bon
eR
at5
Acr
onyc
ine
De
azac
ort
NN
-Dim
ethy
lani
liney
1-( 2
-Hyd
roxy
ethy
l)-1
-nit
roso
urea
z o-
Tolu
idin
eH
Clz
Clit
oral
pre
putia
lM
ouse
11A
ceta
ldeh
yde
met
hylf
orm
ylhy
draz
one
Ben
zene
z 1
3-B
utad
iene
z N
-n-B
utyl
-N-f
orm
ylhy
draz
ine
Dim
ethy
lvin
ylch
lori
dez
N-E
thyl
-N-f
orm
ylhy
draz
ine
glan
dH
exan
alm
ethy
lfor
myl
hydr
azon
e3-
Met
hylb
utan
alm
ethy
lfor
myl
hydr
azon
eP
enta
nalm
ethy
lfor
myl
hydr
azon
eN
-N-P
ropy
l-N
-for
myl
hydr
azin
eT
hio-
tepa
z
Rat
21A
cryl
amid
eC
Id
irec
tblu
e15
24
-Dia
min
oani
sole
sulf
atez
33
-Dim
etho
xybe
nzid
ine
2HC
l3
3-D
imet
hylb
enzi
dine
2H
Clz
Glu
-P-1
z G
lu-P
-2z
Gly
cido
lz IQ
z Is
opho
rone
y M
eIQ
xz 2-
Mer
capt
oben
zoth
iazo
ley
Nal
idix
icac
idy
15-
Nap
htha
lene
diam
inez
5-N
itro-
o-a
nisi
dine
z 5-
Nit
roac
enap
hthe
nez
p-N
itro
benz
oic
acid
y 1-
Nitr
opyr
ene
CI
aci
dre
d11
41
23-
Tri
chlo
ropr
opan
ez T
rp-P
-2ac
etat
ez
Ear
Zym
balrsquos
glan
dM
ouse
3B
enze
nez
Chl
orop
rene
z C
upfe
rron
z
Rat
41A
cryl
onit
rile
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
Azo
xym
etha
neB
enze
nez
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez C
Id
irec
tblu
e15
N-n
-But
yl-N
-nitr
osou
rea
Chl
oram
buci
lz C
upfe
rron
z N
-1-D
iace
tam
ido
uore
ne2
4-D
iam
inoa
niso
lesu
lfat
ez 3
3-D
ichl
orob
enzi
dine
25
-Dim
etho
xy-4
-am
inos
tilb
enez
33
-Dim
etho
xybe
nzid
ine
2HC
l3
3-D
imet
hylb
enzi
dine
2H
Clz
N-(
2-Fl
uore
nyl)
-22
2-t
riu
oroa
ceta
mid
eFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z G
lu-P
-1z
Glu
-P-2
z G
lyci
dolz
Hyd
razo
benz
enez
IQz
IQH
Cl
MeI
Qxz
2-M
etho
xy-3
-am
inod
iben
zofu
ran
8-M
etho
xyps
oral
enN
-(N
-Met
hyl-
N-n
itro
soca
rbam
oyl)
-l-o
rnit
hine
44
-Met
hyle
ne-
bis(
2-ch
loro
anili
ne)
5-N
itro-
o-an
isid
inez
5-N
itroa
cena
phth
enez
N-(
9-O
xo-2
-uo
reny
l)ac
etam
ide
Phen
acet
inz
Pre
dnim
usti
neC
Ia
cid
red
114
p-R
osan
iline
HC
lz T
hio-
tepa
z 4
4-T
hiod
iani
line
z b
-Thi
ogua
nine
deox
yrib
osid
e1
23-
Tri
chlo
ropr
opan
ez V
inyl
chlo
ride
z V
inyl
uor
idez
Eso
phag
usH
amst
er2
AF-
2z N
-Nitr
oso-
N-m
ethy
lure
than
eM
ouse
8B
enzo
( a) p
yren
ez 1
2-D
ibro
moe
than
ez N
-Eth
yl-N
-nit
ro-N
-nit
roso
guan
idin
eN
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
3-( 5
-Nit
ro-2
-fur
yl) -
imid
azo(
12-
a) p
yrid
inez
Nitr
osod
ibut
ylam
inez
N-N
itros
ohex
amet
hyle
neim
ine
Vin
ylac
etat
ez
Mon
key
1N
-Nitr
oso-
N-m
ethy
lure
az
Rat
362
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bis
( 23
-dib
rom
opro
pyl)
phos
phat
em
agne
sium
salt
N-n
-But
yl-N
-nitr
osou
rea
Dih
ydro
safr
olez
Dim
ethy
lvin
ylch
lori
dez
Din
itro
soho
mop
iper
azin
eZ
-Eth
yl-O
NN
-azo
xyet
hane
N-M
ethy
l-N
-nitr
o-N
-nit
roso
guan
idin
ez 3-
( 5-N
itro
-2-f
uryl
) -im
idaz
o(1
2-a
) pyr
idin
ez N
-Nitr
oso-
23-
dihy
drox
ypro
pyl-
2-hy
drox
ypro
pyla
min
eN
itro
so-2
3-d
ihyd
roxy
prop
yl-2
-oxo
prop
ylam
ine
N-N
itro
so-(
2-hy
drox
ypro
pyl)
-(2-
hydr
oxye
thyl
) am
ine
N-N
itros
o-N
-met
hyl-
4-u
oroa
nilin
eN
itros
o-N
-met
hyl-
N-(
2-ph
enyl
) eth
ylam
ine
Nitr
oso-
12
36-
tetr
ahyd
ropy
ridi
neN
-Nit
roso
( 22
2-t
riu
oroe
thyl
) eth
ylam
ine
N-N
itros
oall
yl-2
3-d
ihyd
roxy
prop
ylam
ine
N-N
itro
soal
lyl-
2-hy
drox
ypro
pyla
min
eN
-Nit
roso
ally
l-2-
oxop
ropy
lam
ine
Nitr
osoa
myl
uret
han
Nitr
osoa
naba
sine
N-N
itros
obis
( 2-h
ydro
xypr
opyl
) am
ine
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
diet
hyla
min
eN
-Nitr
osod
ipro
pyla
min
eN
itro
soet
hylu
reth
ane
Nit
roso
hept
amet
hyle
neim
ine
N-N
itro
som
ethy
l-2
3-di
hydr
oxyp
ropy
lam
ine
N-N
itros
omet
hyl-
2-hy
drox
ypro
pyla
min
eN
-Nit
roso
met
hyl(
2-ox
opro
pyl)
amin
e2-
Nitr
osom
ethy
lam
inop
yrid
ine
Nit
roso
met
hyla
nili
neN
-Nitr
oson
orni
cotin
e-1-
N-o
xide
N-N
itro
sopi
peri
dine
z N
-Nit
roso
thia
ldin
eN
-Nit
roso
thio
mor
phol
ine
Gal
lbla
dder
Ham
ster
1N
-Met
hyl-
N-f
orm
ylhy
draz
ine
Mou
se4
N-E
thyl
-N-f
orm
ylhy
draz
ine
N-M
ethy
l-N
-for
myl
hydr
azin
e3-
Met
hylb
utan
alm
ethy
lfor
myl
hydr
azon
eN
-N-P
ropy
l-N
-for
myl
hydr
azin
eM
onke
y1
Aa
toxi
nB
y 1H
arde
rian
glan
dM
ouse
19B
enze
nez
Ben
zidi
ne2
HC
l2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
13-
But
adie
nez
Cap
tafo
lz C
hlor
opre
nez
Cup
ferr
onz
Dic
hlor
oace
tyle
nez
Eth
ylen
eox
idez
Gen
tian
viol
etG
lyci
dolz
Iodi
nate
dgl
ycer
olz
Isop
rene
N-M
ethy
lola
cryl
amid
ey N
itro
met
hane
z 4
4-O
xydi
anil
inez
12
3-T
rich
loro
prop
anez
24
6-T
rini
tro-
13-
dim
ethy
l-5-
tert
-but
ylbe
nzen
eV
inyl
uor
idez
Hem
atop
oiet
icM
ouse
53A
ceta
mid
ez A
at
oxin
cru
dez
Ally
liso
vale
rate
z tr
ans-
5-A
min
o-3[
2-( 5
-nitr
o-2-
fury
l)vi
nyl] -
12
4-ox
adia
zole
2-A
min
o-4-
( p-n
itro
phen
yl) t
hiaz
ole
syst
em2-
Am
inoa
nthr
aqui
none
z 5-
Aza
cyti
dine
z A
zath
iopr
ine
Ben
zene
z 1
4-B
enzo
quin
one
Ben
zotr
ichl
orid
eB
enzo
ylhy
draz
ine
13-
But
adie
nez
12-
di-n
-But
ylhy
draz
ine
2HC
lC
apta
folz
Chl
oram
buci
lz C
hlor
inat
edpa
raf
ns( C
234
3ch
lori
ne)y
Cyc
loph
osph
amid
ez D
acar
bazi
nez
DD
Tz
Dib
rom
odul
cito
lz D
ibro
mom
anni
tolz
Est
radi
olm
usta
rdy
Eth
ylen
eox
idez
5-Fl
uoro
urac
ily Fo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z G
entia
nvi
olet
Hex
anam
idey
2-H
ydra
zino
-4-(
p-am
inop
heny
l)th
iazo
lez
2-H
ydra
zino
-4-
( p-n
itro
phen
yl) t
hiaz
olez
1-( 2
-Hyd
roxy
ethy
l)-1
-nit
roso
urea
z IC
RF
-159
z Is
opho
spha
mid
ez Is
opre
neM
eIQ
xz M
elph
alan
z 1-
Met
hyl-
14-
dihy
dro-
7-[ 2
-(5-
nitr
ofur
yl) v
inyl
] -4-
oxo-
18-
naph
thyr
idin
e-3-
carb
oxyl
ate
pota
ssiu
mM
ethy
lmet
hane
sulf
onat
e4
4-M
ethy
lene
dian
ilin
e2H
Clz
Met
roni
dazo
lez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez P
hene
ster
inz
Phe
nolp
htha
lein
z Ph
IPH
Clz
Phor
bol
Proc
arba
zine
HC
lz S
trob
ane
Tetr
auo
roet
hyle
nez
Thi
o-te
paz
p-To
lylu
reay
Tri
s(2-
chlo
roet
hyl)
phos
phat
ez U
reth
anez
CI
vat
yello
w4y
( Con
tinue
don
next
page
)
641
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Mon
key
1P
roca
rbaz
ine
HC
lz
Rat
56A
llyl
isov
aler
atez
1-A
myl
-1-n
itros
oure
aA
traz
iney
Ben
zidi
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
CI
dir
ectb
lue
15
N-n
-But
yl-N
-nitr
osou
rea
Cad
miu
mch
lori
deC
hlor
ambu
cilz
Cyc
loph
osph
amid
ez D
acar
bazi
nez
13-
Dib
utyl
-1-n
itro
sour
eaD
ichl
oroa
cety
lene
z 3
3-D
ichl
orob
enzi
dine
Dic
hlor
vosz
Dim
etho
xane
33
-Dim
etho
xybe
nzid
ine-
44
-dii
socy
anat
ey 3
3-D
imet
hoxy
benz
idin
e2H
Cl
Dim
ethy
lmor
phol
inop
hosp
hora
mid
atey
2-( 2
2-D
imet
hylh
ydra
zino
) -4-
( 5-n
itro-
2-fu
ryl)
thia
zole
Eth
ylen
eox
idez
Form
alde
hyde
z Fo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z F
uran
z G
lyci
dolz
FD
ampC
gree
nno
1y
FDamp
Cgr
een
no2
y H
emat
oxyl
in2
-Hyd
razi
no-4
-(p-
amin
ophe
nyl)
thia
zole
z H
ydro
quin
onez
1-( 2
-Hyd
roxy
ethy
l)-1
-nit
roso
urea
z Io
dina
ted
glyc
erol
z L
asio
carp
ine
2-M
erca
ptob
enzo
thia
zole
y M
etep
aM
ethy
lter
t-bu
tyle
ther
z M
irex
z l-
5-M
orph
olin
omet
hyl-
3-[(
5-ni
trof
urfu
ryli
dene
) am
ino]
-2-o
xazo
lidi
none
H
Cl
Nit
rite
sod
ium
y N
-[5-
( 5-N
itro-
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ryl)
-13
4-t
hiad
iazo
l-2-
yl] a
ceta
mid
ez o-
Nit
roan
isol
ez 1-
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Nitr
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ino]
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itros
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enyl
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ylam
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itros
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than
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ine
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rbaz
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ropa
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ltone
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ropy
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red
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no4
y Te
trac
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ylen
ez Te
tra
uoro
ethy
lene
z T
hio-
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z 2
46-
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chlo
roph
enol
z T
rp-P
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etat
ez
Kid
ney
Ham
ster
1B
rom
ate
pota
ssiu
mz
Mou
se26
o-B
enzy
l-p-
chlo
roph
enol
y 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bro
mat
epo
tass
ium
z B
rom
odic
hlor
omet
hane
z 1
3-B
utad
iene
z 1
2-di
-n-B
utyl
hydr
azin
e2H
Cl
Caf
feic
acid
z C
hlor
ofor
mz
Chl
orop
rene
z D
amin
ozid
ez 2
4-D
iam
inop
heno
l2H
Cly
Dic
hlor
oace
tyle
nez
24-
Din
itrot
olue
ne( c
onta
inin
g1
0-1
52
6-di
nitr
otol
uene
)zH
ydro
quin
onez
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ydro
xy-2
-ace
tyla
min
ouo
rene
z 3-
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roxy
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utyr
ophe
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dide
L
ead
acet
ate
basi
cz M
ercu
rym
ethy
lchl
orid
eN
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acet
icac
idz
Och
rato
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Az
Phe
nace
tinz
CI
pig
men
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3z St
rept
ozot
ocin
z T
ris(
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loro
ethy
l)ph
osph
atez
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez V
inyl
iden
ech
lori
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Mon
key
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dm
ethy
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xym
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teR
at86
A
atox
inB
1y 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 1-
Am
ino-
2-m
ethy
lant
hraq
uino
nez
2-A
min
o-5-
( 5-n
itro-
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ryl)
-13
4-o
xadi
azol
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Am
ino-
5-( 5
-nit
ro-2
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yl) -
13
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iadi
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Am
ino-
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heno
ly 2-
Am
ino-
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HC
lz A
rist
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acid
so
dium
salt
( 77
AA
I21
A
AII
) A
zoxy
met
hane
Bar
bita
lso
dium
Ben
zofu
ranz
Bro
mat
epo
tass
ium
z B
rom
odic
hlor
omet
hane
z te
rt-B
utyl
alco
holz
Caf
feic
acid
z C
apta
folz
Cap
tanz
Chl
orin
ated
para
fns
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60
chlo
rine
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hlor
ofor
mz
3-( p
-Chl
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heny
l)-1
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imet
hylu
reay
Chl
orop
rene
z C
hlor
otha
loni
ly C
inna
myl
anth
rani
late
z C
itrin
inC
oum
arin
z D
ichl
oroa
cety
lene
z 1
4-D
ichl
orob
enze
nez
Die
thyl
acet
amid
e3
4-D
ihyd
roco
umar
inz
Dim
etho
xane
Dim
ethy
lmet
hylp
hosp
hona
tey
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
N-4
-(4
-Flu
orob
iphe
nyl)
acet
amid
eFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z G
lyci
neH
exac
hlor
obut
adie
ne
Hex
achl
oroe
than
ez H
exam
ethy
lmel
amin
e2-
Hyd
razi
no-4
-(5-
nitr
o-2-
fury
l)th
iazo
lez
Hyd
roqu
inon
ez 1-
( 2-H
ydro
xyet
hyl)
-1-n
itro
sour
eaz
Isop
horo
ney
Lea
dac
etat
ey L
ead
acet
ate
basi
cz d-
Lim
onen
ey 2-
Met
hoxy
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min
odib
enzo
fura
n8-
Met
hoxy
psor
alen
Z-M
ethy
l-O
NN
-azo
xyet
hane
Met
hylt
ert-
buty
leth
erz
N-(
N-M
ethy
l-N
-nit
roso
carb
amoy
l)-l
-orn
ithi
nea
-Met
hylb
enzy
lalc
ohol
y M
irex
z l-
5-M
orph
olin
omet
hyl-
3-[(
5-ni
trof
urfu
rylid
ene)
amin
o]-2
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zolid
inon
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Cl
Nit
rilo
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cac
idz
Nit
rilo
tria
cetic
acid
tri
sodi
umsa
ltm
onoh
ydra
tey
3-( 5
-Nitr
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fury
l)-i
mid
azo(
12-
a) p
yrid
inez
N-[
3-( 5
-Nitr
o-2-
fury
l)-1
24
-oxa
diaz
ole-
5-yl
] -m
ethy
l]ac
etam
ide
N-[
5-( 5
-Nitr
o-2-
fury
l)-1
34
-thi
adia
zol-
2-yl
] ace
tam
idez
o-N
itro
anis
olez
Nitr
oben
zene
z 2-
Nit
ro
uore
ne
1-[(
5-N
itrof
urfu
rylid
ene)
amin
o]hy
dant
oinz
1-N
itro
so-1
-hyd
roxy
ethy
l-3-
chlo
roet
hylu
rea
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
diet
hyla
min
eN
-Nitr
osod
imet
hyla
min
ez N
-Nit
roso
pyrr
olid
inez
Och
rato
xin
Az
CI
aci
dor
ange
3y N
-Oxy
diet
hyle
neth
ioca
rbam
yl-N
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diet
hyle
nesu
lfen
amid
eP
hena
cetin
z Ph
enaz
one
Phen
olph
thal
einz
Phen
ylbu
tazo
nez
o-Ph
enyl
phen
ate
sodi
umy
Que
rcet
iny
Salic
ylaz
osul
fapy
ridi
nez
Str
epto
zoto
cinz
Tetr
achl
oroe
thyl
enez
Tetr
auo
roet
hyle
nez
Tetr
ahyd
rofu
ranz
12
3-T
rich
loro
prop
anez
Tri
s(2-
chlo
roet
hyl)
phos
phat
ez T
ris(
23-
dibr
omop
ropy
l)ph
osph
atez
Vin
ylch
lori
dez
Lar
gein
test
ine
Ham
ster
51
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
Hyd
razi
nez
Met
hylh
ydra
zine
Ure
than
ezM
ouse
1C
apsa
icin
Rat
32A
at
oxin
B1y
1-A
llyl
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itros
oure
a1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z A
myl
opec
tin
sulf
ate
Azo
xym
etha
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
te
chni
calg
rade
z C
Id
irec
tblu
e15
Bro
mod
ichl
orom
etha
nez
N-N
-But
yl-n
-nitr
osou
rea
Car
rage
enan
aci
d-de
grad
edC
hrys
azin
z D
extr
ansu
lfat
eso
dium
( DS-
M-1
) 3
3-D
imet
hoxy
benz
idin
e2H
Cl
33
-Dim
ethy
lben
zidi
ne2
HC
lz Z
-Eth
yl-O
NN
-azo
xym
etha
ne1
-Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-t
hiaz
olyl
] hyd
razi
dez
Glu
-P-1
z G
lu-P
-2z
Gly
cido
lz N
-Hex
ylni
tros
oure
a1-
Hyd
roxy
anth
raqu
inon
e1-
( 2-H
ydro
xyet
hyl)
-1-n
itro
sour
eaz
IQz
o-N
itro
anis
olez
N-N
itro
sobi
s(2-
oxop
ropy
l)am
ine
Phe
nazo
pyri
dine
HC
lz P
hIP
HC
lz C
Ia
cid
red
114
44
-Thi
odia
nilin
ez T
ribr
omom
etha
ney
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez
Liv
erD
og2
33
-Dic
hlor
oben
zidi
ne4
4-M
ethy
lene
-bis
( 2-c
hlor
oani
line
)H
amst
er16
2-A
cety
lam
ino
uore
nez
pp
-DD
Ey
12-
Dim
ethy
lhyd
razi
ne2
HC
lH
exac
hlor
oben
zene
z H
ydra
zine
sulf
atez
N-H
ydro
xy-2
-ace
tyla
min
ouo
rene
z N
-Met
hyl-
N-f
orm
ylhy
draz
ine
Met
hylh
ydra
zine
Met
hyln
itros
amin
o-N
N-d
imet
hyle
thyl
amin
eN
-Nitr
oso-
13-
oxaz
olid
ine
Nit
roso
-2-o
xopr
opyl
etha
nola
min
eN
-Nitr
osoa
llyl-
2-ox
opro
pyla
min
eN
-Nit
roso
azet
idin
eN
-Nit
roso
mor
phol
ine
N-N
itros
opip
erid
inez
N-N
itros
opyr
rolid
inez
Mou
se23
1A
-a-C
Ace
tam
inop
henz
2-A
cety
lam
ino
uore
nez
Aci
uor
fen
Ald
rinz
1-A
min
o-2
4-di
brom
oant
hraq
uino
nez
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
1-A
min
o-2-
met
hyla
nthr
aqui
none
z 2-
Am
inoa
nthr
aqui
none
z 4-
Am
inod
iphe
nyl
2-A
min
odip
heny
lene
oxid
e3-
Am
inot
riaz
olez
Ara
mite
z A
rocl
or12
54y
Aur
amin
e-O
z B
enzi
dine
2H
Cl
Ben
zofu
ranz
Ben
zyla
ceta
tey
3-B
enzy
lsyd
none
-4-a
ceta
mid
ez B
is( 2
-chl
oro-
1-m
ethy
leth
yl) e
ther
tec
hnic
algr
adey
Bis
-2-c
hlor
oeth
ylet
her
Bis
-2-h
ydro
xyet
hyld
ithio
carb
amic
acid
pot
assi
umC
Id
irec
tbla
ck38
CI
dir
ectb
lue
218z
HC
blue
no1
z H
Cbl
ueno
1( p
uri
ed)
Bro
mod
ichl
orom
etha
nez
13-
But
adie
nez
But
ylat
edhy
drox
ytol
uene
y 1
1-di
-n-B
utyl
hydr
azin
eC
apta
folz
Car
bazo
le
Car
bon
tetr
achl
orid
ez C
hlor
alhy
drat
eC
hlor
ambe
ny C
hlor
dane
tec
hnic
algr
adey
Chl
oren
dic
acid
z C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
1-
Chl
oro-
2-ni
trob
enze
ney
1-C
hlor
o-4-
nitr
oben
zene
y 4-
Chl
oro-
m-p
heny
lene
diam
inez
4-C
hlor
o-o-
phen
ylen
edia
min
ez 5-
Chl
oro-
o-to
luid
iney
642
[ 4-C
hlor
o-6-
( 23
-xyl
idin
o)-2
-pyr
imid
inyl
thio
] ace
ticac
idz
4-C
hlor
o-6-
( 23
-xyl
idin
o)-2
-pyr
imid
inyl
thio
( N-b
-hyd
roxy
ethy
l)ac
etam
idez
Chl
oroa
ceta
ldeh
yde
p-C
hlor
oani
line
HC
lz C
hlor
oben
zila
tey
Chl
orod
ibro
mom
etha
ney
Chl
orof
orm
z C
hlor
opre
nez
Chr
ysaz
inz
CI-
924
Cin
nam
ylan
thra
nila
tez
Cip
ro
brat
ez C
lobu
zari
ty C
ompo
und
LY17
1883
Cou
mar
inz
p-C
resi
dine
z C
upfe
rron
z C
ycla
mat
eso
dium
y C
yclo
chlo
roti
neC
ypro
tero
neac
etat
ep
p-D
DD
y p
p-D
DE
y D
DT
z D
ialla
te2
4-D
iam
inot
olue
nez
24-
Dia
min
otol
uene
2H
Clz
35-
Dic
hlor
o-( N
-11
-dim
ethy
l-2-
prop
ynyl
) ben
zam
ide
26-
Dic
hlor
o-p-
phen
ylen
edia
min
ey D
ichl
oroa
cetic
acid
z 1
4-D
ichl
orob
enze
nez
12-
Dic
hlor
opro
pane
y D
icof
oly
Die
ldri
nz D
ifta
lone
34
-Dih
ydro
coum
arin
z D
ihyd
rosa
frol
ez 2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 1
1-D
imet
hylh
ydra
zine
y 1
4-D
ioxa
nez
55-
Dip
heny
lhyd
anto
iny
Dip
yron
ey D
oxyl
amin
esu
ccin
atez
Est
rago
led
l-E
thio
nine
z o-
Eth
oxyb
enza
mid
eN
-Eth
yl-N
-for
myl
hydr
azin
eE
thyl
ene
imin
eE
thyl
ene
thio
urea
z 2-
Eth
ylhe
xano
ly di
( 2-E
thyl
hexy
l)ad
ipat
ey di
( 2-E
thyl
hexy
l)ph
thal
atez
4-F
luor
o-4-
amin
odip
heny
lF
uran
z Fu
rfur
alz
Gen
tian
viol
etG
lu-P
-1z
Glu
-P-2
z G
lyci
dolz
Gri
seof
ulvi
nH
CD
Dm
ixtu
rez
Hep
tach
lory
Hex
achl
orob
enze
nez
a-1
23
45
6-H
exac
hlor
ocyc
lohe
xane
z b
-12
34
56
-Hex
achl
oroc
yclo
hexa
nec
-12
34
56
-Hex
achl
oroc
yclo
hexa
ney
Hex
achl
oroc
yclo
hexa
ne
tech
nica
lgra
deH
exac
hlor
oeth
anez
Hex
anal
met
hylf
orm
ylhy
draz
one
Hyd
razi
nesu
lfat
ez H
ydra
zobe
nzen
ez H
ydro
quin
onez
N-H
ydro
xy-2
-ac
etyl
amin
ouo
rene
z 1
-Hyd
roxy
estr
agol
e2-
Hyd
roxy
ethy
lhyd
razi
ne1
-Hyd
roxy
safr
olez
IQz
Ison
iazi
dz Is
opre
neK
epon
ez L
eupe
ptin
Lov
asta
tinL
uteo
skyr
inM
alon
alde
hyde
sod
ium
saltz
MeA
-a-C
acet
atez
MeI
QM
eIQ
xz M
ethi
dath
ion
3-M
etho
xy-4
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inoa
zobe
nzen
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ethy
lter
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tyle
ther
z M
ethy
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fena
pate
z N
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orm
ylhy
draz
ine
3-M
ethy
lbut
anal
met
hylf
orm
ylhy
draz
one
44
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hyle
ne-b
is( 2
-chl
oroa
nili
ne)
2HC
ly M
ethy
lene
chlo
ride
z 4
4-M
ethy
lene
bis(
NN
-dim
ethy
l)be
nzen
amin
ez 4
4-M
ethy
lene
dian
iline
2H
Clz
Met
hylh
ydra
zine
N-M
ethy
lola
cryl
amid
ey M
ethy
lphe
nida
teH
Cly
Mic
hler
rsquoske
tone
z M
irex
z 1
5-N
apht
hale
nedi
amin
ez 2-
Nap
hthy
lam
inez
Nit
hiaz
idez
3-N
itro-
p-ac
etop
hene
tidey
5-N
itro-
o-an
isid
inez
2-N
itro
-p-p
heny
lene
diam
iney
5-N
itro
-o-t
olui
dine
y 5-
Nitr
oace
naph
then
ez o-
Nitr
oani
sole
z N
itrob
enze
nez
6-N
itrob
enzi
mid
azol
ey N
itro
fenz
Nit
rom
etha
nez
Nitr
osod
ibut
ylam
inez
N-N
itros
odim
ethy
lam
inez
p-N
itros
odip
heny
lam
inez
N-N
itro
sohe
xam
ethy
lene
imin
eN
-Nit
roso
pipe
ridi
nez
Non
abro
mob
iphe
nyl
Och
rato
xin
Az
Oxa
zepa
my
44
-Oxy
dian
iline
z Pe
ntac
hlor
oeth
aney
Pent
achl
oron
itrob
enze
ney
23
45
6-Pe
ntac
hlor
ophe
nol(
Dow
icid
eE
C-7
)y 2
34
56-
Pen
tach
loro
phen
olt
echn
ical
grad
ez P
enta
nalm
ethy
lfor
myl
hydr
azon
eP
hena
zopy
ridi
neH
Clz
Phe
noba
rbit
aly
Phen
obar
bita
lso
dium
z Ph
enyl
buta
zone
z o-
Phen
ylen
edia
min
e2H
Clz
Pipe
rony
l-bu
toxi
dez
Pipe
rony
lsul
foxi
dey
Poly
brom
inat
edbi
phen
ylm
ixtu
rez
Prob
enec
idy
N-N
-Pro
pyl-
N-f
orm
ylhy
draz
ine
Damp
Cre
dno
5z
Rif
ampi
ciny
Rip
azep
amy
p-R
osan
iline
HC
lz S
afro
lez
Sali
cyla
zosu
lfap
yrid
inez
Sel
eniu
mdi
ethy
ldith
ioca
rbam
ate
Sel
eniu
msu
lde
z S
trob
ane
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
11
12-
Tetr
achl
oroe
than
ey 1
12
2-Te
trac
hlor
oeth
aney
Tetr
achl
oroe
thyl
enez
Tetr
achl
orvi
npho
sy Te
tra
uoro
-m-p
heny
lene
diam
ine
2HC
ly Te
tra
uoro
ethy
lene
z Te
trah
ydro
fura
nz T
hioa
ceta
mid
ez 4
4-T
hiod
iani
linez
Thi
oura
cilz
Tolu
ene
diis
ocya
nate
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
m-T
olui
dine
HC
ly o-
Tolu
idin
eH
Clz
p-To
luid
ine
HC
ly To
xaph
eney
T-2
toxi
nT
riam
tere
ney
Tri
chlo
roac
etic
acid
y 2
46-
Tri
chlo
roan
iline
y 1
12-
Tri
chlo
roet
hane
y T
rich
loro
ethy
lene
z T
rich
loro
ethy
lene
( wit
hout
epic
hlor
ohyd
rin)
y 2
46-
Tri
chlo
roph
enol
z 1
23-
Tri
chlo
ropr
opan
ez T
ri
ural
int
echn
ical
grad
ey 2
45-
Tri
met
hyla
nili
nez
24
5-T
rim
ethy
lani
line
HC
lz 2
46-
Tri
met
hyla
nilin
eH
Clz
24
6-T
rini
tro-
13-
dim
ethy
l-5-
tert
-but
ylbe
nzen
eT
ris(
2-ch
loro
ethy
l)ph
osph
atez
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez T
ris(
2-et
hylh
exyl
) pho
spha
tey
Trp
-P-1
acet
atez
Trp
-P-2
acet
atez
Ure
than
ez V
inyl
carb
amat
eV
inyl
uo
ride
z 2
5-X
ylid
ine
HC
lz C
Id
ispe
rse
yell
ow3z
Zea
rale
none
y
Mon
key
8A
ato
xin
B1y
Cyc
asin
and
met
hyla
zoxy
met
hano
lace
tate
IQ
z N
-Nitr
osod
ieth
ylam
ine
N-N
itro
sodi
prop
ylam
ine
N-N
itro
sopi
peri
dine
z S
teri
gmat
ocys
tinz
Ure
than
ez
Rat
206
Ace
tam
idez
Ace
tam
inop
henz
Ace
toxi
me
2-A
cety
lam
ino
uore
nez
A
atox
icol
A
atox
inB
y 1A
at
oxin
cru
dez
1-A
min
o-2
4-di
brom
oant
hraq
uino
nez
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
1-A
min
o-2-
met
hyla
nthr
aqui
none
z 2-
Am
inoa
nthr
aqui
none
z o-
Am
inoa
zoto
luen
ey 11
-Am
inou
ndec
anoi
cac
idy
Ara
mit
ez A
rocl
or12
60A
uram
ine-
Oz
Azo
xym
etha
neB
emit
radi
ne
Ben
zidi
ne3
-Ben
zyls
ydno
ne-4
-ace
tam
idez
Bis
( 23
-dib
rom
opro
pyl)
phos
phat
em
agne
sium
salt
CI
dir
ectb
lue
15
Bro
mod
ichl
orom
etha
nez
Bud
eson
ide
Cap
tafo
lz C
arbo
nte
trac
hlor
idez
Chl
oren
dic
acid
z C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
4-C
hlor
o-4
-am
inod
iphe
nyle
ther
z 2-
Chl
oro-
5-( 3
5-d
imet
hylp
iper
idin
osul
phon
yl) b
enzo
icac
id[
4-C
hlor
o-6-
( 23
-xy
lidi
no) -
2-py
rim
idin
ylth
io] a
ceti
cac
idz
4-C
hlor
o-6-
( 23
-xyl
idin
o)-2
-pyr
imid
inyl
thio
( N-b
-hyd
roxy
ethy
l)ac
etam
idez
Chl
orob
enze
ney
Chl
orof
orm
z 3-
( p-C
hlor
ophe
nyl)
-11
-dim
ethy
lure
ay C
ipro
bra
tez
Cliv
orin
eC
lob
rate
y C
loph
enA
30C
oum
arin
z p-
Cre
sidi
nez
Cro
tona
ldeh
yde
Cup
ferr
onz
Cyc
lope
ntan
one
oxim
eD
DT
z D
ecab
rom
odip
heny
loxi
dey
Deh
ydro
epia
ndro
ster
one
Deh
ydro
epia
ndro
ster
one
acet
ate
24-
Dia
min
otol
uene
z 2
4-D
iam
inot
olue
ne2
HC
lz 1
2-D
ibro
moe
than
ez D
ichl
oroa
ceti
cac
idz
Dic
hlor
oace
tyle
nez
NN
-Die
thyl
-4-(
4-[
pyri
dyl-
1-o
xide
] azo
) ani
line
Die
thyl
stil
best
rolz
Dim
etho
xane
3
3-D
imet
hoxy
benz
idin
e2H
Cl
56-
Dim
etho
xyst
erig
mat
ocys
tinN
N-D
imet
hyl-
4-am
inoa
zobe
nzen
e6-
Dim
ethy
lam
ino-
44-
diph
enyl
-3-h
epta
nola
ceta
teH
Cly
33
-Dim
ethy
lben
zidi
ne2
HC
lz D
imet
hyln
itram
ine
Din
itros
ohom
opip
eraz
ine
26-
Din
itro
tolu
ene
24-
Din
itrot
olue
ne( c
onta
inin
g1
0-1
52
6-di
nitr
otol
uene
)z
Din
itrot
olue
net
echn
ical
grad
e( 2
4( 7
7) -
and
26
( 19
) -)
14-
Dio
xane
z D
ipen
tyln
itro
sam
ine
Dox
ylam
ine
succ
inat
ez E
thin
yles
trad
iol
Eth
ioni
ne
dl-E
thio
nine
z 4-
Eth
oxy-
phen
ylur
eaE
thyl
alco
holy
Z-E
thyl
-ON
N-a
zoxy
etha
neZ
-Eth
yl-O
NN
-azo
xym
etha
neE
thyl
ene
thio
urea
z di
( 2-E
thyl
hexy
l)ph
thal
atez
Flu
cona
zole
y N
-(2-
Flu
oren
yl) -
22
2-tr
iuo
roac
etam
ide
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-t
hiaz
olyl
] hyd
razi
dez
Fum
onis
inB
1F
uran
z Fu
rfur
alz
Glu
-P-1
z G
lu-P
-2z
FDamp
Cgr
een
no1
y H
CD
Dm
ixtu
rez
Hex
achl
orob
enze
nez
a-1
23
45
6-H
exac
hlor
ocyc
lohe
xane
z H
ydra
zine
z H
ydra
zine
sulf
atez
Hyd
razo
benz
enez
Hyd
roch
loro
uor
ocar
bon
123
N-H
ydro
xy-2
-ace
tyla
min
ouo
rene
z 1-
Hyd
roxy
anth
raqu
inon
e1-
( 2-H
ydro
xyet
hyl)
-nitr
oso-
3-ch
loro
ethy
lure
a1
-Hyd
roxy
safr
olez
IQz
IQH
Cl
Ison
iazi
dz K
epon
ez L
asio
carp
ine
MeA
-a-C
acet
atez
MeI
Qxz
Met
hapy
rile
neH
Cl
Z-M
ethy
l-O
NN
-azo
xyet
hane
Met
hylc
arba
mat
ey M
ethy
lclo
fena
pate
z 3
-Met
hyl-
4-di
met
hyla
min
oazo
benz
ene
2-M
ethy
l-1-
nitr
oant
hraq
uino
nez
4-( 4
-N-M
ethy
l-N
-nit
rosa
min
osty
ryl)
quin
olin
e4
4-M
ethy
lene
-bis
( 2-c
hlor
oani
line
) 4
4-M
ethy
lene
-bis
( 2-m
ethy
lani
line
) 4
4-M
ethy
lene
dian
ilin
e2H
Clz
4-( M
ethy
lnit
rosa
min
o)-1
-(3-
pyri
dyl)
-1-(
buta
none
) M
etro
nida
zole
z M
ichl
errsquos
keto
nez
Mir
exz
Mon
ocro
tali
neN
afen
opin
Nit
rite
sod
ium
y N
itrob
enze
nez
2-N
itro
buta
ne2
-Nit
ro
uore
ne3
-Nit
rope
ntan
eN
-Nitr
oso-
bis-
( 44
4-t
ri
uoro
-N-b
utyl
) am
ine
1-N
itros
o-5
6-di
hydr
oura
cil
N-N
itro
so-2
3-d
ihyd
roxy
prop
ylet
hano
lam
ine
1-N
itros
o-1-
hydr
oxye
thyl
-3-c
hlor
oeth
ylur
ea1
-Nitr
oso-
1-( 2
-hyd
roxy
prop
yl) -
3-ch
loro
ethy
lure
aN
-Nitr
oso-
( 2-h
ydro
xypr
opyl
) -( 2
-hyd
roxy
ethy
l)am
ine
N-N
itros
o-N
-met
hyl-
N-d
odec
ylam
ine
Nit
roso
-N-m
ethy
l-N
-(2-
phen
yl) e
thyl
amin
e
( Con
tinue
don
next
page
)
643
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
N-N
itro
so-N
-met
hyld
ecyl
amin
e3-
Nit
roso
-2-o
xazo
lidin
one
Nit
roso
-2-o
xopr
opyl
etha
nola
min
eN
itro
so-1
23
6-t
etra
hydr
opyr
idin
eN
-Nit
roso
ally
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itro
soal
lyl-
2-ox
opro
pyla
min
eN
-Nitr
osoa
llyl
etha
nola
min
eN
-Nit
roso
bis(
2-ox
opro
pyl)
amin
eN
itro
sodi
buty
lam
inez
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
diet
hyla
min
eN
-Nitr
osod
imet
hyla
min
ez p-
Nitr
osod
iphe
nyla
min
ez N
-Nit
roso
dipr
opyl
amin
eN
itros
odod
ecam
ethy
lene
imin
eN
-Nit
roso
ephe
drin
eN
itro
soet
hylm
ethy
lam
ine
Nitr
osoh
epta
met
hyle
neim
ine
N-N
itros
omet
hyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nit
roso
met
hyl-
( 2-h
ydro
xyet
hyl)
amin
eN
-Nitr
osom
ethy
l-( 3
-hyd
roxy
prop
yl) a
min
eN
-Nitr
osom
ethy
l(2-
oxop
ropy
l)am
ine
N-N
itro
som
ethy
l-( 2
-tos
ylox
yeth
yl) a
min
eN
itro
som
ethy
lund
ecyl
amin
eN
-Nit
roso
mor
phol
ine
N-N
itros
opip
erid
inez
N-N
itro
sopy
rrol
idin
ez N
-Nit
roso
thia
ldin
eo-
Nit
roso
tolu
ene
Nor
lest
rinz
N-(
9-O
xo-2
-uo
reny
l)ac
etam
ide
44
-Oxy
dian
iline
z 2
34
56-
Pent
achl
orop
heno
lte
chni
calg
rade
z P
etas
iten
ine
Phe
noba
rbit
als
odiu
mz
1-P
heny
lazo
-2-n
apht
holy
o-P
heny
lene
diam
ine
2HC
lz P
iper
onyl
buto
xide
z P
olyb
rom
inat
edbi
phen
ylm
ixtu
rez
Pre
dnis
olon
eP
yril
amin
em
alea
tey
CI
aci
dre
d11
4C
Ip
igm
entr
ed3z
Damp
Cre
dno
5z
Damp
Cre
dno
9y
FD
ampC
red
no1
p-
Ros
anili
neH
Clz
Saf
role
z Se
leni
umsu
lde
z Se
nkir
kine
Ste
rigm
atoc
ystin
z S
ymph
ytin
eTa
mox
ifen
citr
atez
Telo
neII
tec
hnic
algr
adez
33
44
-Te
traa
min
obip
heny
l4H
Clz
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tetr
auo
roet
hyle
nez
Thi
oace
tam
idez
44
-Thi
odia
nilin
ez To
luen
edi
isoc
yana
te
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
Tri
amci
nolo
neac
eton
ide
24
5-T
rim
ethy
lani
line
z 2
45-
Tri
met
hyla
nili
neH
Clz
24
6-T
rim
ethy
lani
line
HC
lz T
rini
trog
lyce
rin
Trp
-P-1
acet
atez
Trp
-P-2
acet
atez
Vin
ylac
etat
ez V
inyl
brom
ide
Vin
ylch
lori
dez
Vin
yl
uori
dez
CI
dis
pers
eye
llow
3z
Tre
esh
rew
1A
ato
xin
B1y
Lun
gH
amst
er3
Met
hyln
itro
sam
ino-
NN
-dim
ethy
leth
ylam
ine
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
1-N
itro
so-3
45
-tri
met
hylp
iper
azin
eM
ouse
116
Ace
tald
ehyd
em
ethy
lfor
myl
hydr
azon
eN
-Ace
tyl-
4-( h
ydro
xym
ethy
l)ph
enyl
hydr
azin
e1-
Ace
tyl-
2-is
onic
otin
oylh
ydra
zine
A
llyl
hydr
azin
eH
Cl
1-A
min
o-2
4-di
brom
oant
hraq
uino
nez
Are
coli
neH
Cl
5-A
zacy
tidi
nez
Ben
zene
z B
enzo
fura
nz B
enzo
tric
hlor
ide
Ben
zoyl
hydr
azin
eB
enzy
lhyd
razi
ne2
HC
l2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bis
( 2-c
hlor
o-1-
met
hyle
thyl
) eth
er
tech
nica
lgra
dey
Bis
-(ch
loro
met
hyl)
ethe
rz 1
3-B
utad
iene
z N
-n-B
utyl
-N-f
orm
ylhy
draz
ine
But
ylat
edhy
drox
ytol
uene
y 1
1-di
-n-B
utyl
hydr
azin
en-
But
ylhy
draz
ine
HC
l1
2-di
-N-B
utyl
hydr
azin
e2H
Cl
Caf
feic
acid
z C
arba
myl
hydr
azin
eH
Cl
1-C
arba
myl
-2-p
heny
lhyd
razi
neC
hlor
ambu
cilz
Chl
orop
rene
z C
obal
tsul
fate
hept
ahyd
rate
z C
oum
arin
z C
yclo
phos
pham
idez
Dac
arba
zine
z D
amin
ozid
ez p
p-D
DD
y D
DT
z 1
1-D
iall
ylhy
draz
ine
12-
Dia
llyl
hydr
azin
e2H
Cl
Dib
enz(
ah)
anth
race
ne1
2-D
ibro
mo-
3-ch
loro
prop
anez
Dib
rom
odul
cito
lz 1
2-D
ibro
moe
than
ez D
ibro
mom
anni
tolz
12-
Dic
hlor
oeth
anez
12-
Dif
orm
ylhy
draz
ine
Dih
ydro
safr
olez
25-
Dim
etho
xy-4
-am
inos
tilbe
nez
33
-Dim
ethy
lben
zidi
ne2
HC
lz 1
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
a-E
cdys
one
Est
radi
olm
usta
rdy
N-E
thyl
-N-f
orm
ylhy
draz
ine
Eth
ylen
eim
ine
Eth
ylen
eox
idez
Eth
ylhy
draz
ine
HC
l5-
Flu
orou
raci
ly Fo
rmyl
hydr
azin
eG
lyci
dolz
c-1
23
45
6-H
exac
hlor
ocyc
lohe
xane
y H
exan
alm
ethy
lfor
myl
hydr
azon
eH
ydra
zine
z H
ydra
zine
sulf
atez
IQz
Isob
utyl
nitr
itez
Ison
iazi
dz Is
onic
otin
icac
idva
nilly
liden
ehyd
razi
de
Isop
rene
Lov
asta
tinM
eIQ
xz M
elph
alan
z 1-
Met
hyl-
14-
dihy
dro-
7-[ 2
-(5-
nitr
ofur
yl) v
inyl
] -4-
oxo-
18-
naph
thyr
idin
e-3-
carb
oxyl
ate
pota
ssiu
m
N-M
ethy
l-N
-for
myl
hydr
azin
eM
ethy
lmet
hane
sulf
onat
e3-
Met
hylb
utan
alm
ethy
lfor
myl
hydr
azon
eM
ethy
lene
chlo
ride
z M
ethy
lhyd
razi
ne
Met
hylh
ydra
zine
sulf
ate
( N-6
) -( M
ethy
lnit
roso
) ade
nine
(N
-6) -
( Met
hyln
itro
so) a
deno
sine
N-M
ethy
lola
cryl
amid
ey M
etro
nida
zole
z M
olyb
denu
mtr
ioxi
dey
Mon
oace
tylh
ydra
zine
Nap
htha
lene
15
-Nap
htha
lene
diam
inez
Nic
otin
icac
idhy
draz
ide
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez 3-
Nitr
o-3-
hexe
nez
Nit
robe
nzen
ez N
itrom
etha
nez
Nit
roso
dibu
tyla
min
ez N
-Nit
roso
dim
ethy
lam
inez
N-N
itros
ohex
amet
hyle
neim
ine
N-N
itro
sopi
peri
dine
z O
zone
y Pe
ntan
alm
ethy
lfor
myl
hydr
azon
en-
Pen
tylh
ydra
zine
HC
lPh
enes
teri
nz Ph
enyl
ethy
lhyd
razi
nesu
lfat
eP
roca
rbaz
ine
HC
lz N
-N-P
ropy
l-N
-for
myl
hydr
azin
eP
ropy
lhyd
razi
neH
Cl
Sel
eniu
msu
lde
z S
trep
tozo
toci
nz Su
lfal
late
z Te
lone
IIt
echn
ical
grad
ez 3
34
4-T
etra
amin
obip
heny
l4H
Clz
Tetr
anitr
omet
hane
z T-
2to
xin
Tri
chlo
roet
hyle
nez
Tri
ura
lint
echn
ical
grad
ey 2
45-
Tri
met
hyla
nilin
eH
Clz
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez U
reth
anez
Vin
ylch
lori
dez
Vin
ylu
orid
ez V
inyl
iden
ech
lori
dey
24-
Xyl
idin
eH
Cly
Mon
key
1U
reth
anez
Rat
551-
Ally
l-1-
nitr
osou
rea
2-A
min
o-5-
( 5-n
itro
-2-f
uryl
) -1
34-
oxad
iazo
le2
-Am
ino-
5-( 5
-nitr
o-2-
fury
l)-1
34
-thi
adia
zole
2-A
min
o-5-
nitr
othi
azol
ey 1-
Am
yl-1
-nitr
osou
rea
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
is-(
chlo
rom
ethy
l)et
herz
HC
blue
no1
z B
rom
oeth
anez
N-n
-But
yl-N
-nit
roso
urea
Cad
miu
mch
lori
deC
adm
ium
sulp
hate
( 11
) 1-
Chl
oroe
thyl
nitr
oso-
3-( 2
-hyd
roxy
prop
yl) u
rea
Chl
orop
rene
z C
obal
tsul
fate
hept
ahyd
rate
z 1
2-D
ibro
moe
than
ez D
imet
hylh
ydro
gen
phos
phit
ey tr
ans-
2-[(
Dim
ethy
lam
ino)
met
hylim
ino]
-5-
[ 2-(
5-ni
tro-
2-fu
ryl)
viny
l] -1
34-
oxad
iazo
le3
3-D
imet
hylb
enzi
dine
2H
Clz
12-
Epo
xybu
tane
y 1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
N-H
exyl
nitr
osou
rea
Hyd
razi
nez
Hyd
razi
nesu
lfat
ez 1-
( 2-H
ydro
xyet
hyl)
-1-n
itro
sour
eaz
Isob
utyl
nitr
itez
Ison
iazi
dz 4
4-M
ethy
lene
-bi
s(2-
chlo
roan
iline
) 4-
( Met
hyln
itros
amin
o)-1
-(3-
pyri
dyl)
-1-b
utan
ol4
-(M
ethy
lnit
rosa
min
o)-1
-(3-
pyri
dyl)
-1-(
buta
none
) N
-[ 3
-(5-
Nitr
o-2-
fury
l)-
12
4-ox
adia
zole
-5-y
l] -m
ethy
lace
tam
ide
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
3-N
itro-
3-he
xene
z 5-
Nitr
oace
naph
then
ez N
-Nit
roso
-bis
-(4
44-
tri
uoro
-N-b
utyl
) am
ine
N-N
itros
o-N
-met
hyl-
N-d
odec
ylam
ine
N-N
itros
o-N
-met
hyl-
N-t
etra
decy
lam
ine
N-N
itro
so-N
-met
hyld
ecyl
amin
eN
-Nitr
oso-
N-m
ethy
lure
az N
-Nitr
osob
is( 2
-hyd
roxy
prop
yl)
amin
eN
-Nitr
osob
is-2
3-d
ihyd
roxy
prop
ylam
ine
( 2-o
xopr
opyl
) am
ine
Nitr
osod
ibut
ylam
inez
N-N
itros
odim
ethy
lam
inez
N-N
itro
soep
hedr
ine
Nitr
osoe
thyl
met
hyla
min
eN
-Nit
roso
met
hyl
N-N
itro
som
ethy
l-( 3
-hyd
roxy
prop
yl) a
min
eN
itro
som
ethy
lund
ecyl
amin
eC
Ia
cid
red
114
Sod
ium
dich
rom
ate
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tetr
anit
rom
etha
nez
24
5-T
rim
ethy
lani
line
z 2
46-
Tri
met
hyla
nili
neH
Clz
Vin
ylch
lori
dez
Mam
mar
ygl
and
Dog
1Ly
nest
reno
lH
amst
er1
Vin
ylch
lori
dez
Mou
se24
5-A
zacy
tidin
ez B
enze
nez
CI
dir
ectb
lack
381
3-B
utad
iene
z C
alci
fero
lC
hlor
opre
nez
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
Die
thyl
stilb
estr
olz
a-E
cdys
one
Est
radi
olE
thyl
ene
oxid
ez F
uros
emid
ey G
lyci
dolz
Gri
seof
ulvi
nIs
onia
zidz
Ison
icot
inic
acid
vani
llylid
eneh
ydra
zide
( N
-6) -
( Met
hyln
itros
o)ad
enos
ine
Nitr
oben
zene
z R
eser
pine
z Su
lfal
late
z V
inyl
chlo
ride
z V
inyl
uor
idez
Vin
ylid
ene
chlo
ride
y
644
Rat
102
4-A
cety
lam
inob
iphe
nyl
2-A
cety
lam
ino
uore
nez
Acr
onyc
ine
Acr
ylam
ide
Acr
ylon
itri
leA
F-2
z 1-
Ally
l-1-
nitr
osou
rea
2-A
min
o-5-
( 5-n
itro-
2-fu
ryl)
-13
4-
oxad
iazo
le2
-Am
ino-
5-( 5
-nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
e2-
Am
ino-
5-ni
trot
hiaz
oley
4-A
min
odip
heny
lHC
l1-
Am
yl-1
-nit
roso
urea
Atr
azin
ey B
emit
radi
ne
Ben
zidi
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
4-B
is( 2
-hyd
roxy
ethy
l)am
ino-
2-( 5
-nit
ro-2
-thi
enyl
) qui
nazo
line
13-
But
adie
nez
N-n
-But
yl-N
-nitr
osou
rea
Cap
tafo
lz C
arbo
nte
trac
hlor
idez
Car
boxy
met
hyln
itros
oure
aC
hlor
ambu
cilz
Chl
orop
rene
z C
ytem
bena
y D
acar
bazi
nez
N-1
-Dia
ceta
mid
ouo
rene
46
-Dia
min
o-2-
( 5-n
itro-
2-fu
ryl)
-S-t
riaz
ine
24-
Dia
min
oani
sole
sulf
atez
24-
Dia
min
otol
uene
z 1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dib
rom
oman
nito
lz 1
3-D
ibut
yl-1
-nit
roso
urea
33
-Dic
hlor
oben
zidi
ne1
2-D
ichl
oroe
than
ez 3
3-D
imet
hoxy
benz
idin
e2H
Cl
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
12-
Dim
ethy
l-5-
nitr
oim
idaz
ole
tran
s-2-
[(D
imet
hyla
min
o)m
ethy
limin
o]-5
-[2-
( 5-n
itro
-2-f
uryl
) vin
yl] -
13
4-ox
adia
zole
Dim
ethy
lam
inoe
thyl
nitr
osoe
thyl
urea
nitr
ite
salt
33
-Dim
ethy
lben
zidi
ne2
HC
lz 2-
( 22
-Dim
ethy
lhyd
razi
no) -
4-( 5
-nitr
o-2-
fury
l)th
iazo
le
24-
Din
itro
tolu
ene
( con
tain
ing
10-
15
24-
Dio
xane
z 1-
Eth
ylni
tros
o-3-
( 2-h
ydro
xyet
hyl)
-ure
a1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
6-di
nitr
otol
uene
)zN
-(2-
Fluo
reny
l)-2
22
-tri
uo
roac
etam
ide
Form
icac
id2-
( 4-m
ethy
l-2-
thia
zoly
l)hy
draz
ide
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-
thia
zoly
l] hyd
razi
dez
Gly
cido
lz H
exam
ethy
lmel
amin
eN
-Hex
ylni
tros
oure
a2-
Hyd
razi
no-4
-(p-
amin
ophe
nyl)
thia
zole
z 2-
Hyd
razi
no-4
-( 5
-nit
ro-2
-fur
yl) t
hiaz
olez
2-H
ydra
zino
-4-(
p-ni
trop
heny
l)th
iazo
lez
Hyd
razo
benz
enez
1-( 2
-Hyd
roxy
ethy
l)-3
-[( 5
-nit
rofu
rfur
ylid
ene)
amin
o]-2
-im
idaz
olid
inon
e1-
( 2-H
ydro
xyet
hyl)
-nit
roso
-3-e
thyl
urea
1-(
2-H
ydro
xyet
hyl)
-1-n
itros
oure
az In
dom
etha
cin
IQz
IQH
Cl
Ison
iazi
dz 2-
Met
hoxy
-3-a
min
odib
enzo
fura
n4-
Met
hyl-
1-[(
5-ni
trof
urfu
rylid
ene)
amin
o]-2
-im
idaz
olid
inon
eN
-(N
-Met
hyl-
N-n
itro
soca
rbam
oyl)
-l-o
rnit
hine
3-M
ethy
lcho
lant
hren
e4
4-M
ethy
lene
-bi
s(2-
chlo
roan
iline
) 4
4-M
ethy
lene
-bis
( 2-m
ethy
lani
line)
Met
hyle
nech
lori
dez
Met
roni
dazo
lez
l-5-
Mor
phol
inom
ethy
l-3-
[(5-
nitr
ofur
fury
lide
ne) a
min
o]-
2-ox
azol
idin
one
HC
lN
ithia
zide
z 5-
Nitr
o-2-
fura
ldeh
yde
sem
icar
bazo
nez
3-( 5
-Nitr
o-2-
fury
l)-i
mid
azo(
12-
a)
pyri
dine
z 4-
( 5-N
itro-
2-fu
ryl)
thia
zole
N
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] ace
tam
ide
NN
-[6-
( 5-N
itro
-2-f
uryl
) -S-
tria
zine
-24
-diy
l] bis
acet
amid
e5-
Nitr
oace
naph
then
ez 1-
[(5-
Nit
rofu
rfur
ylid
ene)
amin
o]-2
-im
idaz
olid
inon
eN
itrom
etha
nez
1-N
itrop
yren
eN
orle
stri
nz O
chra
toxi
nA
z N
-(9-
Oxo
-2-
uore
nyl)
acet
amid
ePh
enac
etin
z Ph
enes
teri
nz Ph
IPH
Clz
Proc
arba
zine
HC
lz Pr
opan
esu
lton
e1
2-Pr
opyl
ene
oxid
ez St
yren
ey Su
lfal
late
z 4
4-S
ulfo
nylb
isac
etan
ilid
eTo
luen
edi
isoc
yana
te
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
o-T
olui
dine
HC
lz 1
23-
Tri
chlo
ropr
opan
ez 2
22-
Tri
uor
o-N
-[4-
( 5-n
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] ace
tam
idez
Trp
-P-2
acet
atez
Vin
ylch
lori
dez
FD
ampC
viol
etno
1y
Mes
ovar
ium
Rat
2Sa
lbut
amol
Ter
buta
line
Myo
card
ium
Mou
se2
Est
radi
olm
usta
rdy
Phen
este
rinz
Nas
alca
vity
bB
ush
baby
1N
-Nitr
osod
ieth
ylam
ine
Ham
ster
11A
ceta
ldeh
yde
Dia
llyln
itros
amin
eD
imet
hylc
arba
myl
chlo
ride
Hyd
razi
nez
Met
hyln
itro
sam
ino-
NN
-dim
ethy
leth
ylam
ine
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
N-N
itro
soal
lyl-
2-ox
opro
pyla
min
eN
-Nitr
osom
ethy
l-2
3-di
hydr
oxyp
ropy
lam
ine
N-N
itros
omor
phol
ine
N-N
itros
onor
nico
tine
N-N
itros
opip
erid
inez
Mou
se6
Ally
lgly
cidy
leth
ery
12-
Dib
rom
o-3-
chlo
ropr
opan
ez 1
2-D
ibro
moe
than
ez Fo
rmal
dehy
dez
N-N
itro
sohe
xam
ethy
lene
imin
e1
2-Pr
opyl
ene
oxid
ez
Rat
43A
ceta
ldeh
yde
Acr
ylon
itril
e1-
Azo
xypr
opan
eB
enze
nez
Bis
-(ch
loro
met
hyl)
ethe
rz p-
Cre
sidi
nez
Dia
llyln
itros
amin
e1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dim
ethy
lnitr
amin
eD
imet
hylv
inyl
chlo
ride
z D
initr
osoh
omop
iper
azin
e1
4-D
ioxa
nez
12-
Epo
xybu
tane
y Z
-Eth
yl-O
NN
-azo
xyet
hane
E
thyl
benz
ene
Eth
ylni
tros
ocya
nam
ide
Form
alde
hyde
z H
exam
ethy
lpho
spho
ram
ide
Hyd
razi
nez
N-N
itro
so-N
-met
hyld
ecyl
amin
edi
( N-N
itro
so) -
perh
ydro
pyri
mid
ine
N-N
itros
o(2
22-
tri
uoro
ethy
l)et
hyla
min
e1-
Nitr
oso-
34
5-tr
imet
hylp
iper
azin
eN
-Nitr
osoa
llyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nit
roso
ally
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itro
soal
lyle
than
olam
ine
N-N
itros
obis
( 2-h
ydro
xypr
opyl
) am
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
dipr
opyl
amin
eN
itros
oeth
ylm
ethy
lam
ine
N-N
itros
omet
hyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nitr
osom
ethy
l-( 2
-hyd
roxy
ethy
l)am
ine
N-N
itro
som
ethy
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itros
omet
hyl(
2-ox
opro
pyl)
amin
eN
-Nit
roso
norn
icot
ine-
1-N
-oxi
de
N-N
itro
sopi
peri
dine
z P
hena
cetin
z Ph
enyl
glyc
idyl
ethe
r1
2-Pr
opyl
ene
oxid
ez V
inyl
acet
atez
Vin
ylch
lori
dez
Ner
vous
Mou
se3
13-
But
adie
nez
N-N
itros
odim
ethy
lam
inez
Pro
carb
azin
eH
Clz
syst
emR
at21
Acr
ylam
ide
Acr
ylon
itril
eB
rom
oeth
anez
Chl
oram
buci
lz 1-
( 4-C
hlor
ophe
nyl)
-1-p
heny
l-2-
prop
ynyl
carb
amat
eC
yclo
phos
pham
idez
1-E
thyl
-1-n
itros
oure
aE
thyl
eneo
xide
z 1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
eaG
lu-P
-1z
Glu
-P-2
z G
lyci
dolz
R(
) -2-
Met
hyl-
N-n
itro
sopi
peri
dine
S(
) -2-
Met
hyl-
N-n
itro
sopi
peri
dine
M
ethy
lnit
ram
ine
N-N
itros
o-N
-met
hylu
reaz
N-N
itros
odie
than
olam
ine
1-P
heny
l-3
3-di
met
hyltr
iaze
neP
roca
rbaz
ine
HC
lz P
ropa
nesu
ltone
Vin
ylch
lori
dez
Ora
lcav
ityc
Ham
ster
4A
ceta
ldeh
yde
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
N-N
itros
omor
phol
ine
N-N
itro
sopi
peri
dine
z
Mou
se3
N-N
itros
ohex
amet
hyle
neim
ine
12
3-T
rich
loro
prop
anez
Vin
ylac
etat
ez
Rat
32A
cryl
amid
eA
cryl
onitr
ile
Ben
zene
z 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
CI
dir
ectb
lue
15C
Id
irec
tblu
e21
8z C
hlor
opre
nez
3-D
iazo
tyra
min
eH
Cl
12-
Dib
rom
o-3-
chlo
ropr
opan
ez 3
3-D
imet
hoxy
benz
idin
e2H
Cl
33
-Dim
ethy
lben
zidi
ne2
HC
lz D
imet
hylv
inyl
chlo
ride
z D
initr
osoh
omop
iper
azin
eG
lyci
dolz
IQz
MeA
-a-C
acet
atez
N-N
itros
o-2
3-di
hydr
oxyp
ropy
l-2-
hydr
oxyp
ropy
lam
ine
Nit
roso
-23
-dih
ydro
xypr
opyl
-2-
oxop
ropy
lam
ine
Nitr
oso-
N-m
ethy
l-N
-(2-
phen
yl) e
thyl
amin
eN
itro
soam
ylur
etha
nN
-Nitr
osod
ieth
ylam
ine
Nit
roso
ethy
lure
than
N
itros
ohep
tam
ethy
lene
imin
e1-
Nitr
osoh
ydan
toin
N-N
itros
omet
hyl(
2-ox
opro
pyl)
amin
eN
-Nit
roso
thia
ldin
eN
-Nitr
osot
hiom
orph
olin
eC
Ia
cid
red
114
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tolu
eney
12
3-T
rich
loro
prop
anez
Xyl
ene
mix
ture
( m-x
ylen
eo-
xyle
nep
-xyl
ene)
Ova
ryM
ouse
10B
enze
nez
13-
But
adie
nez
Die
thyl
stil
best
rolz
N-M
ethy
lola
cryl
amid
ey 5-
Nitr
o-2-
fura
ldeh
yde
sem
icar
bazo
nez
5-N
itroa
cena
phth
enez
1-[(
5-N
itro
furf
uryl
iden
e)am
ino]
hyda
ntoi
nz P
heno
lpht
hale
inz
Tam
oxif
enci
trat
ez 4-
Vin
ylcy
cloh
exen
ePa
ncre
asH
amst
er3
Nitr
oso-
23-
dihy
drox
ypro
pyl-
2-ox
opro
pyla
min
eN
itro
so-2
6-d
imet
hylm
orph
olin
eN
itro
so-2
-oxo
prop
ylet
hano
lam
ine
Mon
key
1U
reth
anez
Rat
222-
Am
ino-
5-ni
trop
heno
ly 1-
( Am
inom
ethy
l)cy
cloh
exan
eace
ticac
idA
zase
rine
But
ylbe
nzyl
phth
alat
ey C
hlor
endi
cac
idz
Cin
nam
ylan
thra
nila
tez
Clo
bra
tey
Dic
hlor
vosz
Eth
ylal
coho
ly H
ydro
chlo
ro
uoro
carb
on12
3IQ
HC
lM
alon
alde
hyde
sod
ium
saltz
MeA
-a-C
acet
atez
2-M
erca
ptob
enzo
thia
zole
y M
ethy
lclo
fena
pate
z N
-(N
-Met
hyl-
N-n
itros
ocar
bam
oyl)
-l-o
rnit
hine
4-(
Met
hyln
itro
sam
ino)
-1-(
3-py
ridy
l)-1
-but
anol
4-(
Met
hyln
itros
amin
o)-1
-( 3
-pyr
idyl
) -1-
( but
anon
e)N
afen
opin
Nitr
ofen
z To
luen
edi
isoc
yana
tec
omm
erci
algr
ade
( 24
( 80
) -an
d2
6( 2
0) -
)z1
23
-Tri
chlo
ropr
opan
ez
Peri
tone
alM
ouse
8B
is-1
2-(
chlo
rom
etho
xy) e
than
eB
is-1
4-(
chlo
rom
etho
xy) -
p-xy
lene
Bis
-(ch
loro
met
hyl)
ethe
rz C
hlor
opre
nez
tran
s-1
4-D
ichl
orob
uten
e-2
cavi
tyD
imet
hylc
arba
myl
chlo
ride
Phe
noxy
benz
amin
eH
Clz
Tri
s-1
23-
( chl
orom
etho
xy) p
ropa
neR
at22
Acr
onyc
ine
Acr
ylam
ide
Act
inom
ycin
DA
nili
neH
Cly
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
rom
ate
pota
ssiu
mz
Chl
oroz
otoc
in
Cyt
embe
nay
Dap
sone
y 1
2-D
ibro
moe
than
ez D
ibro
mom
anni
tolz
33
-Dim
ethy
lben
zidi
ne2
HC
lz 1
4-D
ioxa
nez
Eth
ylen
eox
idez
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Gly
cido
lz M
elph
alan
z N
-Met
hyl-
N4
-din
itros
oani
line
Mit
omyc
in-C
N-N
itro
so-2
24
-tri
met
hyl-
12-
dihy
droq
uino
line
poly
mer
Ph
enox
yben
zam
ine
HC
lz o-
Tolu
idin
eH
Clz
( Con
tinue
don
next
page
)
645
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Pitu
itar
ygl
and
Mou
se8
Die
thyl
stil
best
rolz
Eno
vid
Eth
ylen
eth
iour
eaz
Iodi
nate
dgl
ycer
olz
Isop
rene
Nor
lest
rinz
Pro
pylt
hiou
raci
lz Z
eara
leno
ney
Rat
73-
Am
inot
riaz
olez
12-
Dib
rom
oeth
anez
Die
thyl
stil
best
rolz
Eth
ylal
coho
ly 2-
Mer
capt
oben
zoth
iazo
ley
Met
roni
dazo
lez
Nor
lest
rinz
Pros
tate
Rat
4C
adm
ium
chlo
ride
N-N
itros
obis
( 2-h
ydro
xypr
opyl
) am
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
PhIP
HC
lz
Skin
Ham
ster
2U
reth
anez
Vin
ylch
lori
dez
Mou
se5
5-A
zacy
tidin
ez 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Chl
orop
rene
z G
lyci
dolz
Thi
o-te
paz
Rat
332-
Ace
tyla
min
ouo
rene
z 3-
Am
ino-
9-et
hylc
arba
zole
mix
ture
z 1-
Azo
xypr
opan
e2-
Azo
xypr
opan
eB
enze
nez
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
ol
tech
nica
lgra
dez
CI
dir
ectb
lue
15C
arbo
xym
ethy
lnitr
osou
rea
24-
Dia
min
oani
sole
sulf
atez
Dib
rom
odul
cito
lz D
ibro
mom
anni
tolz
Dim
etho
xane
2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 3
3-D
imet
hoxy
benz
idin
e-4
4-d
iisoc
yana
tey
33
-Dim
etho
xybe
nzid
ine
2HC
l3
3-D
imet
hylb
enzi
dine
2H
Clz
Dim
ethy
lvin
ylch
lori
dez
24-
Din
itro
tolu
ene
( con
tain
ing
10-
15
26-
dini
trot
olue
ne)z
1-E
thyl
nitr
oso-
3-( 2
-hyd
roxy
ethy
l)-u
rea
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Gly
cido
lz 1-
( 2-H
ydro
xyet
hyl)
-nit
roso
-3-e
thyl
urea
IQ
z L
asio
carp
ine
MeI
Qxz
N-(
N-M
ethy
l-N
-nitr
osoc
arba
moy
l)-l
-orn
ithi
ne
5-N
itro-
o-an
isid
inez
CI
aci
dre
d11
4p-
Ros
anili
neH
Clz
Thi
o-te
paz
Thi
oure
ay V
inyl
chlo
ride
z F
Damp
Cvi
olet
no1
y
Smal
lint
esti
neM
ouse
6C
apta
folz
Cap
tanz
N-E
thyl
-N-n
itro
-N-n
itro
sogu
anid
ine
Hyd
roge
npe
roxi
deN
-Met
hyl-
N-n
itro-
N-n
itros
ogua
nidi
nez
N-(
Tri
chlo
rom
ethy
lthi
o)ph
thal
imid
eM
onke
y1
Ure
than
ez
Rat
29A
cryl
onitr
ile
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
is( 2
3-d
ibro
mop
ropy
l)ph
osph
ate
mag
nesi
umsa
lt4
-Bis
( 2-h
ydro
xyet
hyl)
amin
o-2-
( 5-n
itro
-2-t
hien
yl) q
uina
zolin
eC
Id
irec
tblu
e15
Car
boxy
met
hyln
itros
oure
a1-
( 4-C
hlor
ophe
nyl)
-1-p
heny
l-2-
prop
ynyl
carb
amat
e2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 3
3-D
imet
hoxy
benz
idin
e2H
Cl
46-
Dim
ethy
l-2-
( 5-n
itro
-2-f
uryl
)py
rim
idin
etr
ans-
2-[(
Dim
ethy
lam
ino)
met
hylim
ino]
-5-[
2-( 5
-nit
ro-2
-fur
yl) v
inyl
] -1
34-
oxad
iazo
le3
3-D
imet
hylb
enzi
dine
2H
Clz
Z-E
thyl
-ON
N-a
zoxy
met
hane
1-E
thyl
-1-n
itros
oure
aFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z G
lu-P
-1z
Glu
-P-2
z IQ
z L
asio
carp
ine
N-M
ethy
l-N
-nitr
o-N
-nitr
osog
uani
dine
z N
-[5-
( 5-N
itro-
2-fu
ryl)
-13
4-t
hiad
iazo
l-2-
yl] a
ceta
mid
ez N
-Nitr
oso-
N-i
sobu
tylu
rea
3-N
itro
so-2
-oxa
zoli
dino
neN
itro
soet
hylu
reth
ane
PhI
PH
Clz
Pro
pane
sulto
neQ
uerc
etin
y C
Ia
cid
red
114
Trp
-P-2
acet
atez
Sple
enR
at7
Ani
line
HC
ly A
zobe
nzen
ey p-
Chl
oroa
nili
neH
Clz
Dap
sone
y o-
Nitr
osot
olue
neD
ampC
red
no9
y o-
Tolu
idin
eH
Clz
Stom
ach
Ham
ster
18A
F-2z
14-
Din
itros
o-2
6-di
met
hylp
iper
azin
eFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z H
ydra
zine
z N
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
N-[
4-( 5
-Nitr
o-2-
fury
l)-2
-thi
azol
yl] a
ceta
mid
eN
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] for
mam
idez
N-N
itro
so-2
3-d
ihyd
roxy
prop
yl-2
-hyd
roxy
prop
ylam
ine
Nitr
oso-
23-
dihy
drox
ypro
pyl-
2-ox
opro
pyla
min
eN
-Nitr
oso-
ethy
l-2-
oxop
ropy
lure
aN
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aN
itros
o-5-
met
hylo
xazo
lidon
eN
-Nit
roso
-N-m
ethy
lure
than
N-N
itros
o-1
3-ox
azol
idin
eN
-Nit
roso
-2-p
heny
leth
ylur
ea1
-Nit
roso
-34
5-t
rim
ethy
lpip
eraz
ine
Ure
than
ez V
inyl
chlo
ride
z
Mou
se63
Ace
tald
ehyd
em
ethy
lfor
myl
hydr
azon
eA
ciu
orfe
nA
F-2
z 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 2-
Am
ino-
4-( 5
-nitr
o-2-
fury
l)th
iazo
lez
tran
s-5-
Am
ino-
3[2-
( 5-n
itro-
2-fu
ryl)
viny
l] -1
24-
oxad
iazo
leA
reco
line
HC
lB
enza
ldeh
ydey
Ben
zofu
ranz
Ben
zotr
ichl
orid
eB
enzy
lace
tate
y B
enzy
lchl
orid
ey B
rom
oeth
anol
13
-But
adie
nez
But
ylat
edhy
drox
yani
sole
z 1
1-di
-N-B
utyl
hydr
azin
eC
affe
icac
idz
Cap
tafo
lz C
arba
zole
Cat
echo
lz 3-
Chl
oro-
2-m
ethy
lpro
pene
tec
hnic
algr
ade
( con
tain
ing
5di
met
hylv
inyl
chlo
ride
)z3
-(C
hlor
omet
hyl)
pyri
dine
HC
lz C
hlor
opre
nez
2-C
hlor
opro
pana
l1-
Chl
orop
rope
neC
ypro
tero
neac
etat
e1
1-D
ially
lhyd
razi
ne1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dic
hlor
vosz
Dig
lyci
dylr
esor
cino
leth
ert
echn
ical
grad
ez D
imet
hylv
inyl
chlo
ride
z D
init
roso
pipe
razi
neE
stra
diol
mus
tard
y E
thyl
acry
late
z Fo
rmic
acid
2-[ 4
-( 5
-nit
ro-2
-fur
yl) -
2-th
iazo
lyl] h
ydra
zide
z G
lyci
dolz
2-H
ydra
zino
-4-(
5-ni
tro-
2-fu
ryl)
thia
zole
z N
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
ICI
1628
46z
IQz
Isop
rene
Lov
asta
tin
MeI
Q1
-Met
hyl-
14-
dihy
dro-
7-[ 2
-(5-
nitr
ofur
yl) v
inyl
] -4-
oxo-
18-
naph
thyr
idin
e-3-
carb
oxyl
ate
pota
ssiu
m3
-(5-
Nitr
o-2-
fury
l)-
imid
azo(
12-
a) p
yrid
inez
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
N-[
4-( 5
-Nitr
o-2-
fury
l)-2
-thi
azol
yl] f
orm
amid
ez N
-Nit
roso
-N
-met
hylu
reaz
Nit
roso
dibu
tyla
min
ez N
-Nit
roso
hexa
met
hyle
neim
ine
N-N
itros
opip
erid
inez
b-P
ropi
olac
tone
z Se
sam
olz
Sty
rene
oxid
ez Te
lone
IIt
echn
ical
grad
ez N
-(T
rich
loro
met
hylth
io) p
htha
limid
e1
23-
Tri
chlo
ropr
opan
ez 2
22-
Tri
uo
ro-N
-[4-
( 5-n
itro
-2-f
uryl
) -2-
thia
zoly
l]ac
etam
idez
Tri
ur
alin
tec
hnic
algr
adey
Tri
s(2-
chlo
roet
hyl)
phos
phat
ez T
ris(
23-
dibr
omop
ropy
l)ph
osph
atez
Vin
ylac
etat
ez
Rat
85A
ceto
ne[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zone
1-A
ceto
xysa
frol
ey A
cryl
onitr
ile
1-A
llyl
-1-n
itro
sour
ea2
-Am
ino-
5-( 5
-nit
ro-2
-fur
yl) -
13
4-ox
adia
zole
2-
Am
ino-
5-( 5
-nitr
o-2-
fury
l)-1
34
-thi
adia
zole
2-A
min
o-4-
( 5-n
itro
-2-f
uryl
) thi
azol
ez 1-
Am
yl-1
-nit
roso
urea
Ari
stol
ochi
cac
id
sodi
umsa
lt( 7
7A
AI
21
AA
II)
Ben
zene
z B
enzo
( a) p
yren
ez 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bis
( 23
-dib
rom
opro
pyl)
phos
phat
em
agne
sium
salt
BL
-634
1H
Cl
N-n
-But
yl-N
-nitr
osou
rea
But
ylat
edhy
drox
yani
sole
z b
-But
yrol
acto
neC
affe
icac
idz
Cat
echo
lz 3-
Chl
oro-
2-m
ethy
lpro
pene
tec
hnic
algr
ade
( con
tain
ing
5di
met
hylv
inyl
chlo
ride
)z4
-Chl
oro-
o-ph
enyl
ened
iam
inez
Chl
oro
uoro
met
hane
3-
( Chl
orom
ethy
l)py
ridi
neH
Clz
Cip
rob
rate
z C
upfe
rron
z 1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
Dig
lyci
dylr
esor
cino
leth
ert
echn
ical
grad
ez 2
5-D
imet
hoxy
-4-a
min
osti
lben
ez D
imet
hylh
ydro
gen
phos
phit
ey 4
6-D
imet
hyl-
2-( 5
-nit
ro-2
-fu
ryl)
pyri
mid
ine
tran
s-2-
[(D
imet
hyla
min
o)m
ethy
limin
o]-5
-[2-
( 5-n
itro
-2-f
uryl
) vin
yl] -
13
4-ox
adia
zole
Dim
ethy
lvin
ylch
lori
dez
Epi
chlo
rohy
drin
y E
thyl
acry
late
z E
thyl
ene
oxid
ez 2-
Flu
oroe
thyl
-nitr
osou
rea
Gly
cido
lz N
-Hex
ylni
tros
oure
a1-
Hyd
roxy
anth
raqu
inon
e1-
( 2-H
ydro
xyet
hyl)
-1-
nitr
osou
reaz
1-( 3
-Hyd
roxy
prop
yl) -
1-ni
tros
oure
a1
-Hyd
roxy
safr
olez
ICI
1628
46z
Lox
tidin
eL
upit
idin
e3H
Cl
Mer
curi
cch
lori
dey
3-M
etho
xyca
tech
ol4
-Met
hoxy
phen
olN
-Met
hyl-
N-n
itro-
N-n
itros
ogua
nidi
nez
N-M
ethy
l-N
-nit
roso
benz
amid
e4-
Met
hylc
atec
hol
Met
hyln
itro
socy
anam
ide
3-( 5
-Nit
ro-2
-fur
yl) -
imid
azo(
12-
a) p
yrid
inez
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
4-( 5
-Nit
ro-2
-fur
yl) t
hiaz
ole
2-N
itro
uo
rene
8-N
itro
quin
olin
eN
itro
so-B
aygo
nN
-Nit
roso
-23
-dih
ydro
xypr
opyl
-2-h
ydro
xypr
opyl
amin
eN
itros
o-2
3-di
hydr
oxyp
ropy
l-2-
oxop
ropy
lam
ine
1-N
itro
so-3
5-d
imet
hyl-
4-be
nzoy
lpip
eraz
ine
N-N
itro
so-N
-met
hyl-
N-d
odec
ylam
ine
Nitr
oso-
N-m
ethy
l-N
-(2-
phen
yl) e
thyl
amin
eN
-Nit
roso
-N-m
ethy
ldec
ylam
ine
N-N
itro
so-N
-met
hylu
reaz
Nit
roso
-12
36
-tet
rahy
drop
yrid
ine
N-N
itro
sobe
nzth
iazu
ron
Nitr
osod
ibut
ylam
inez
N-N
itros
odie
thyl
amin
eN
-Nit
roso
ephe
drin
eN
itros
oeth
ylur
etha
nO
mep
razo
ley
Phen
acet
inz
Piv
alol
acto
ney
b-P
ropi
olac
tone
z N
-Pro
pyl-
N-n
itro
-N-n
itro
sogu
anid
ine
12-
Pro
pyle
neox
idez
Ses
amol
z St
yren
eox
idez
Sulf
alla
tez
Telo
neII
tec
hnic
algr
adez
12
3-T
rich
loro
prop
anez
24
6-T
rim
ethy
lani
line
HC
lz
646
Subc
utan
eous
Mou
se4
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 1
2-D
ibro
moe
than
ez N
2-c
-Glu
tam
yl-p
-hyd
razi
nobe
nzoi
cac
idG
lyci
dolz
tissu
eR
at13
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 2
4-D
iam
inot
olue
ne2
HC
lz 1
2-D
ichl
oroe
than
ez D
imet
hoxa
ne1
4-D
ioxa
nez
MeA
-a-C
acet
atez
44
-Met
hyle
ne-b
is( 2
-met
hyla
nili
ne)
o-N
itro
soto
luen
ep-
Ros
anili
neH
Clz
Tolu
ene
diis
ocya
nate
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
o-T
olui
dine
HC
lz 2
45-
Tri
met
hyla
nilin
eH
Clz
25-
Xyl
idin
eH
Clz
Test
isM
ouse
4D
ieth
ylst
ilbe
stro
lz Fi
nast
erid
eR
eser
pine
z Ta
mox
ifen
citr
atez
Rat
185-
Aza
cytid
inez
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 1
3-B
utad
iene
z N
-But
yl-N
-(4-
hydr
oxyb
utyl
) nitr
osam
ine
Cad
miu
mch
lori
de
2-C
hlor
o-1
11-
tri
uoro
etha
ne1
1-D
ichl
oro-
1-u
oroe
than
eH
ydro
chlo
rou
oroc
arbo
n12
3M
ethy
lter
t-bu
tyle
ther
z M
ethy
lclo
fena
pate
z M
etro
nida
zole
z N
-Nit
roso
dim
ethy
lam
inez
Oxo
linic
acid
y SD
Z20
0-11
01
11
2-Te
tra
uoro
etha
ney
Tri
chlo
roet
hyle
nez
Tri
nitr
ogly
ceri
nV
inyl
chlo
ride
z
Thy
roid
glan
dH
amst
er4
Hex
achl
orob
enze
nez
Hyd
razi
nez
Met
hylt
hiou
raci
lU
reth
anez
Mou
se18
3-A
min
o-4-
etho
xyac
etan
ilide
y H
Cbl
ueno
1z
tert
-But
ylal
coho
lz C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
24
-Dia
min
oani
sole
sulf
atez
Die
thyl
stil
best
rolz
Dox
ylam
ine
succ
inat
ez E
thio
nam
idey
Eth
ylen
eth
iour
eaz
44
-Met
hyle
nedi
anil
ine
2HC
lz 1
5-N
apht
hale
nedi
amin
ez N
itrob
enze
nez
Oxa
zepa
my
44
-Oxy
dian
iline
z C
Ip
igm
entr
ed3z
Sulf
amet
hazi
ne2
37
8-T
etra
chlo
rodi
benz
o-p-
diox
inz
44
-Thi
odia
nilin
ez
Rat
33A
cryl
amid
e3-
Am
inot
riaz
olez
o-A
nisi
dine
HC
lz B
emit
radi
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bro
mat
epo
tass
ium
z C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
Chl
orop
rene
z 2
4-D
iam
inoa
niso
lesu
lfat
ez N
N-D
ieth
ylth
iour
eay
1-E
thyl
-1-n
itro
sour
ea
Eth
ylen
eth
iour
eaz
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Flu
vast
atin
Gly
cido
lz Io
dina
ted
glyc
erol
z Is
obut
eney
Mal
onal
dehy
des
odiu
msa
ltz
Met
him
azol
e4
4-M
ethy
lene
bis(
NN
-dim
ethy
l)be
nzen
amin
ez 4
4-M
ethy
lene
dian
iline
2H
Clz
Mir
exp
hoto
-N
itro
benz
enez
N-N
itro
sobi
s(2-
oxop
ropy
l)am
ine
44
-Oxy
dian
iline
z Pr
opyl
thio
urac
ilz p-
Ros
anil
ine
HC
lz 2
37
8-Te
trac
hlor
odib
enzo
-p-d
ioxi
nz 4
4-T
hiod
iani
linez
Thi
oura
cilz
Tri
met
hylt
hiou
reay
Vin
ylac
etat
ez Z
inc
dim
ethy
ldith
ioca
rbam
atez
Uri
nary
blad
der
Dog
23
3-D
ichl
orob
enzi
dine
44
-Met
hyle
ne-b
is( 2
-chl
oroa
nilin
e)H
amst
er3
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-t
hiaz
olyl
] hyd
razi
dez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
acet
amid
eN
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] for
mam
idez
Mou
se12
2-A
cety
lam
ino
uore
nez
4-A
min
odip
heny
l2-
Am
inod
iphe
nyle
neox
ide
o-A
nisi
dine
HC
lz 4-
Chl
oro-
4-a
min
odip
heny
leth
erz
p-C
resi
dine
z 4-
Eth
ylsu
lpho
nyln
apht
hale
ne-1
-sul
fona
mid
eN
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez P
hena
cetin
z Te
lone
IIt
echn
ical
grad
ez U
raci
lz
Mon
key
12-
Nap
hthy
lam
inez
Rat
49A
ceta
min
ophe
nz A
llyli
soth
iocy
anat
ey 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 2-
Am
ino-
4-( 5
-nitr
o-2-
fury
l)th
iazo
lez
4-A
min
o-2-
nitr
ophe
noly
11-A
min
ound
ecan
oic
acid
y o-
Ani
sidi
neH
Clz
Ari
stol
ochi
cac
ids
odiu
msa
lt( 7
7A
AI
21
AA
II)
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez C
Id
ispe
rse
blue
1y N
-But
yl-N
-(4-
hydr
oxyb
utyl
) nitr
osam
ine
4-C
hlor
o-o-
phen
ylen
edia
min
ez m
-Cre
sidi
ney
p-C
resi
dine
z C
yclo
phos
pham
idez
Die
thyl
ene
glyc
olD
imet
hyla
rsin
icac
idy
Fose
tylA
lIQ
HC
lM
eA-a
-Cac
etat
ez M
elam
iney
2-M
etho
xy-3
-am
inod
iben
zofu
ran
2-N
apht
hyla
min
ez N
itril
otri
acet
icac
idz
Nitr
ilot
riac
etic
acid
tri
sodi
umsa
ltm
onoh
ydra
tey
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez o-
Nitr
oani
sole
z N
-Nitr
oso-
N-m
ethy
l-N
-dod
ecyl
amin
eN
-Nitr
oso-
N-m
ethy
l-N
-tet
rade
cyla
min
eN
-Nit
roso
-N-m
ethy
ldec
ylam
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
Nitr
osod
ibut
ylam
inez
N-N
itro
sodi
phen
ylam
iney
o-N
itros
otol
uene
N-O
xydi
ethy
lene
thio
carb
amyl
-N-o
xydi
ethy
lene
sulf
enam
ide
Phe
nace
tinz
Phen
azon
eo-
Phen
ylph
enat
eso
dium
y o-
Phen
ylph
enol
y P
otas
sium
bica
rbon
ate
Purp
urin
Que
rcet
iny
p-Q
uino
nedi
oxim
ey Sa
ccha
rin
sodi
umy
Sali
cyla
zosu
lfap
yrid
inez
o-To
luen
esul
fona
mid
eo-
Tolu
idin
eH
Clz
Trp
-P-2
acet
atez
Ura
cilz
Ute
rus
Ham
ster
1N
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aM
ouse
12B
rom
oeth
anez
Chl
oroe
than
ey D
acar
bazi
nez
12-
Dic
hlor
oeth
anez
Die
thyl
stil
best
rolz
Eth
ylen
eox
idez
Gly
cido
lz ( N
-6) -
( Met
hyln
itros
o)ad
enos
ine
Proc
arba
zine
HC
lz 1
23-
Tri
chlo
ropr
opan
ez T
rim
ethy
lpho
spha
tey
Vin
ylac
etat
ez
Rat
26A
cryl
amid
e1-
Ally
l-1-
nitr
osou
rea
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
1-A
myl
-1-n
itros
oure
aA
traz
iney
CI
dir
ectb
lue
15B
rom
ocri
ptin
em
esyl
atey
N-n
-But
yl-N
-nit
roso
urea
Cal
cium
valp
roat
eC
apta
nz 2-
Chl
oro-
11
1-tr
iuo
roet
hane
Dac
arba
zine
z D
amin
ozid
ez 3
3-D
imet
hoxy
benz
idin
e-4
4-d
iisoc
yana
tey
33
-Dim
etho
xybe
nzid
ine
2HC
lD
imet
hyla
min
oeth
ylni
tros
oeth
ylur
ean
itri
tesa
lt1-
Eth
ylni
tros
o-3-
( 2-h
ydro
xyet
hyl)
-ure
a1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
N-H
exyl
nitr
osou
rea
ICR
F-1
59z
Isop
hosp
ham
idez
15-
Nap
htha
lene
diam
inez
Nit
robe
nzen
ez N
orle
stri
nz 4
4-T
hiod
iani
linez
Vin
ylac
etat
ez
Vag
ina
Mou
se1
AZ
Tz
Rat
2A
ZT
z N
-n-B
utyl
-N-n
itro
sour
ea( C
ontin
ued
onne
xtpa
ge)
647
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Vas
cula
rsy
stem
Ham
ster
91
2-D
imet
hylh
ydra
zine
2H
Cl
Gly
cido
lz H
exac
hlor
oben
zene
z N
-Nit
roso
-eth
yl-2
-oxo
prop
ylur
eaN
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aN
-Nitr
oso-
oxop
ropy
lchl
oroe
thyl
urea
N-N
itro
so-o
xopr
opyl
urea
N-N
itros
o-2-
phen
ylet
hylu
rea
Vin
ylch
lori
dez
Mou
se59
A-a
-CN
-Ace
tyl-
4-( h
ydro
xym
ethy
l)ph
enyl
hydr
azin
e1-
Ace
tyl-
2-ph
enyl
hydr
azin
eA
llyl
hydr
azin
eH
Cl
Are
colin
eH
Cl
Aza
thio
prin
eB
enzi
dine
2H
Cl
2-B
iphe
nyla
min
eH
Cly
13-
But
adie
nez
Cap
tafo
lz C
arba
myl
hydr
azin
eH
Cl
4-C
hlor
o-4
-am
inod
iphe
nyle
ther
z 1-
Chl
oro-
4-ni
trob
enze
ney
5-C
hlor
o-o-
tolu
idin
ey 4-
Chl
oro-
o-to
luid
ine
HC
ly p-
Chl
oroa
nilin
eH
Clz
Chl
orop
rene
z C
upfe
rron
z D
acar
bazi
nez
Dam
inoz
idez
24-
Dia
min
otol
uene
2H
Clz
12-
Dib
rom
oeth
anez
Dif
talo
ne7
12-
Dim
ethy
lben
z(a)
anth
race
ne1
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
N-E
thyl
-N-f
orm
ylhy
draz
ine
Eth
ylhy
draz
ine
HC
lG
lu-P
-1z
Glu
-P-2
z p-
Hyd
razi
nobe
nzoi
cac
idH
Cl
1-H
ydro
xysa
frol
ez Is
opre
neM
eA-a
-Cac
etat
ez N
-Met
hyl-
N-f
orm
ylhy
draz
ine
2-M
ethy
l-1-
nitr
oant
hraq
uino
nez
Mic
hler
rsquoske
tone
z 5-
Nitr
o-o-
tolu
idin
ey N
itro
fenz
N-N
itros
o-N
-met
hylu
reaz
Pent
achl
oroa
niso
lez
23
45
6-Pe
ntac
hlor
ophe
nol(
Dow
icid
eE
C-7
)y2
34
56
-Pen
tach
loro
phen
olt
echn
ical
grad
ez n-
Pen
tylh
ydra
zine
HC
lPh
enyl
ethy
lhyd
razi
nesu
lfat
ePh
enyl
hydr
azin
eH
Cl
Ster
igm
atoc
ysti
nz Te
tra
uoro
ethy
lene
z To
luen
edi
isoc
yana
tec
omm
erci
algr
ade
( 24
( 80
) -an
d2
6( 2
0) -
)zo
-Tol
uidi
neH
Clz
24
6-T
rich
loro
anil
iney
24
5-T
rim
ethy
lani
line
HC
lz 2
46-
Tri
met
hyla
nili
neH
Clz
Ure
than
ez V
inyl
carb
amat
eV
inyl
chlo
ride
z V
inyl
uor
idez
Vin
ylid
ene
chlo
ride
y 2
5-X
ylid
ine
HC
lz
Mon
key
2A
ato
xin
B1y
Ure
than
ez
Rat
32A
nilin
eH
Cly
Azo
benz
eney
Ben
zene
z C
livor
ine
Cup
ferr
onz
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
Z-E
thyl
-ON
N-a
zoxy
etha
neZ
-Eth
yl-O
NN
-azo
xym
etha
neI
QH
Cl
Las
ioca
rpin
e4
4-M
ethy
lene
-bis
( 2-c
hlor
oani
line)
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
N-N
itros
o-( 2
-hyd
roxy
prop
yl) -
( 2-h
ydro
xyet
hyl)
amin
eN
itro
so-1
23
6-t
etra
hydr
opyr
idin
eN
-Nitr
osob
is( 2
-oxo
prop
yl) a
min
eN
-Nit
roso
diet
hano
lam
ine
N-N
itro
sodi
ethy
lam
ine
N-N
itros
odim
ethy
lam
inez
N-N
itros
omet
hyl-
( 2-t
osyl
oxye
thyl
) am
ine
N-N
itros
omor
phol
ine
N-N
itro
sopy
rrol
idin
ez Pe
tasi
teni
neS
teri
gmat
ocys
tinz
Sym
phyt
ine
Tetr
auo
roet
hyle
nez
o-To
luid
ine
HC
lz T
rp-P
-2ac
etat
ez V
inyl
brom
ide
Vin
ylch
lori
dez
Vin
yl
uori
dez
aT
here
was
nore
port
edta
rget
site
in1
spec
ies
( rat
sor
mic
e)fo
r5
chem
ical
sw
ithsu
pers
crip
tsb
utth
ech
emic
alw
asev
alua
ted
byth
epu
blis
hed
auth
oras
aca
rcin
ogen
ald
rinz
diel
drin
z N
-nit
roso
pyrr
olid
inez
23
45
6-pe
ntac
hlor
ophe
nol
( Dow
icid
eE
C-7
)ya
ndur
etha
nez
bN
asal
cavi
tyin
clud
estis
sues
ofth
eno
sen
asal
turb
inat
esp
aran
asal
sinu
ses
and
trac
hea
c Ora
lcav
ityin
clud
estis
sues
ofth
em
outh
oro
phar
ynx
phar
ynx
and
lary
nx
Ach
emic
alis
liste
dun
der
each
orga
nev
alua
ted
aspo
sitiv
ein
anex
peri
men
tin
that
spec
ies
byat
leas
t1au
thor
The
refo
rea
chem
ical
may
beli
sted
unde
rse
vera
ltar
geto
rgan
san
dev
ery
chem
ical
liste
din
the
tabl
eis
posi
tive
inat
leas
t1sp
ecie
sIn
orde
rto
com
pare
resu
ltsin
rats
and
mic
esy
mbo
lsfo
llow
chem
ical
ste
sted
inbo
thsp
ecie
sa
zin
dica
tes
that
the
chem
ical
ispo
sitiv
eat
som
esi
tein
both
spec
ies
and
ay
indi
cate
sth
atit
was
test
edin
both
butp
ositi
vein
only
1a
Nth
enu
mbe
rof
chem
ical
sw
ithat
leas
t1po
sitiv
ete
stat
that
site
inth
atsp
ecie
sB
ecau
sem
any
chem
ical
sin
duce
tum
ors
atm
ore
than
1si
tein
agi
ven
spec
ies
man
ych
emic
als
appe
arm
ore
than
once
inth
eta
ble
648
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649
species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters
RESULTS IN RATS AND MICE
For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens
TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database
Chemicals evaluated as carcinogenic in
Rats Mice
All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)
Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2
a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not
b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats
All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical
to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included
The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site
Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common
650 GOLD ET AL TOXICOLOGIC PATHOLOGY
TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)
Target site Agent mixture or industrial process
Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e
Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke
Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products
Brain Vinyl chloride a
Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e
Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena
Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system
Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as
a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell
lymphotropic virus type I (HTLV-I) Vinyl chloridea
Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production
Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)
Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea
Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea
Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)
Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea
Mesenchymal tumors Azathioprinea
Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust
Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust
Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid
(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke
Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production
8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots
Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e
Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays
IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD
IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no
tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance
is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651
sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites
Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to
be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)
Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)
Target Organs of Human CarcinogensTo complement the compendium of target organs in car-
cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke
In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)
Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens
Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from
bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)
ACKNOWLEDGMENTS
We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention
REFERENCES
1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56
2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600
3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998
4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685
5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404
6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605
7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246
8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100
9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash
23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC
11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the
652 GOLD ET AL TOXICOLOGIC PATHOLOGY
US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240
12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute
13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program
14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX
15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11
16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash
34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c
Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Adr
enal
glan
dH
amst
er1
Ure
than
ez
Mou
se8
Car
bon
tetr
achl
orid
ez F
uran
z 4
4-M
ethy
lene
dian
iline
2H
Clz
Pen
tach
loro
anis
olez
23
45
6-Pe
ntac
hlor
ophe
nol(
Dow
icid
eE
C-7
)y
23
45
6-P
enta
chlo
roph
enol
tec
hnic
algr
adez
p-R
osan
ilin
eH
Clz
11
2-T
rich
loro
etha
ney
Rat
16B
rom
oeth
anez
4-C
hlor
o-m
-phe
nyle
nedi
amin
ez C
obal
tsul
fate
hept
ahyd
rate
z 1
2-D
ibro
mo-
3-ch
loro
prop
anez
Die
thyl
stilb
estr
olz
Eth
ylal
coho
ly In
dolid
anI
som
azol
e2-
Mer
capt
oben
zoth
iazo
ley
Mir
exz
Pen
tach
loro
anis
olez
Phe
nolp
htha
lein
z 1
2-Pr
opyl
ene
oxid
ez C
Ip
igm
entr
ed3z
Res
erpi
nez
Ret
inol
acet
ate
Bon
eR
at5
Acr
onyc
ine
De
azac
ort
NN
-Dim
ethy
lani
liney
1-( 2
-Hyd
roxy
ethy
l)-1
-nit
roso
urea
z o-
Tolu
idin
eH
Clz
Clit
oral
pre
putia
lM
ouse
11A
ceta
ldeh
yde
met
hylf
orm
ylhy
draz
one
Ben
zene
z 1
3-B
utad
iene
z N
-n-B
utyl
-N-f
orm
ylhy
draz
ine
Dim
ethy
lvin
ylch
lori
dez
N-E
thyl
-N-f
orm
ylhy
draz
ine
glan
dH
exan
alm
ethy
lfor
myl
hydr
azon
e3-
Met
hylb
utan
alm
ethy
lfor
myl
hydr
azon
eP
enta
nalm
ethy
lfor
myl
hydr
azon
eN
-N-P
ropy
l-N
-for
myl
hydr
azin
eT
hio-
tepa
z
Rat
21A
cryl
amid
eC
Id
irec
tblu
e15
24
-Dia
min
oani
sole
sulf
atez
33
-Dim
etho
xybe
nzid
ine
2HC
l3
3-D
imet
hylb
enzi
dine
2H
Clz
Glu
-P-1
z G
lu-P
-2z
Gly
cido
lz IQ
z Is
opho
rone
y M
eIQ
xz 2-
Mer
capt
oben
zoth
iazo
ley
Nal
idix
icac
idy
15-
Nap
htha
lene
diam
inez
5-N
itro-
o-a
nisi
dine
z 5-
Nit
roac
enap
hthe
nez
p-N
itro
benz
oic
acid
y 1-
Nitr
opyr
ene
CI
aci
dre
d11
41
23-
Tri
chlo
ropr
opan
ez T
rp-P
-2ac
etat
ez
Ear
Zym
balrsquos
glan
dM
ouse
3B
enze
nez
Chl
orop
rene
z C
upfe
rron
z
Rat
41A
cryl
onit
rile
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
Azo
xym
etha
neB
enze
nez
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez C
Id
irec
tblu
e15
N-n
-But
yl-N
-nitr
osou
rea
Chl
oram
buci
lz C
upfe
rron
z N
-1-D
iace
tam
ido
uore
ne2
4-D
iam
inoa
niso
lesu
lfat
ez 3
3-D
ichl
orob
enzi
dine
25
-Dim
etho
xy-4
-am
inos
tilb
enez
33
-Dim
etho
xybe
nzid
ine
2HC
l3
3-D
imet
hylb
enzi
dine
2H
Clz
N-(
2-Fl
uore
nyl)
-22
2-t
riu
oroa
ceta
mid
eFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z G
lu-P
-1z
Glu
-P-2
z G
lyci
dolz
Hyd
razo
benz
enez
IQz
IQH
Cl
MeI
Qxz
2-M
etho
xy-3
-am
inod
iben
zofu
ran
8-M
etho
xyps
oral
enN
-(N
-Met
hyl-
N-n
itro
soca
rbam
oyl)
-l-o
rnit
hine
44
-Met
hyle
ne-
bis(
2-ch
loro
anili
ne)
5-N
itro-
o-an
isid
inez
5-N
itroa
cena
phth
enez
N-(
9-O
xo-2
-uo
reny
l)ac
etam
ide
Phen
acet
inz
Pre
dnim
usti
neC
Ia
cid
red
114
p-R
osan
iline
HC
lz T
hio-
tepa
z 4
4-T
hiod
iani
line
z b
-Thi
ogua
nine
deox
yrib
osid
e1
23-
Tri
chlo
ropr
opan
ez V
inyl
chlo
ride
z V
inyl
uor
idez
Eso
phag
usH
amst
er2
AF-
2z N
-Nitr
oso-
N-m
ethy
lure
than
eM
ouse
8B
enzo
( a) p
yren
ez 1
2-D
ibro
moe
than
ez N
-Eth
yl-N
-nit
ro-N
-nit
roso
guan
idin
eN
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
3-( 5
-Nit
ro-2
-fur
yl) -
imid
azo(
12-
a) p
yrid
inez
Nitr
osod
ibut
ylam
inez
N-N
itros
ohex
amet
hyle
neim
ine
Vin
ylac
etat
ez
Mon
key
1N
-Nitr
oso-
N-m
ethy
lure
az
Rat
362
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bis
( 23
-dib
rom
opro
pyl)
phos
phat
em
agne
sium
salt
N-n
-But
yl-N
-nitr
osou
rea
Dih
ydro
safr
olez
Dim
ethy
lvin
ylch
lori
dez
Din
itro
soho
mop
iper
azin
eZ
-Eth
yl-O
NN
-azo
xyet
hane
N-M
ethy
l-N
-nitr
o-N
-nit
roso
guan
idin
ez 3-
( 5-N
itro
-2-f
uryl
) -im
idaz
o(1
2-a
) pyr
idin
ez N
-Nitr
oso-
23-
dihy
drox
ypro
pyl-
2-hy
drox
ypro
pyla
min
eN
itro
so-2
3-d
ihyd
roxy
prop
yl-2
-oxo
prop
ylam
ine
N-N
itro
so-(
2-hy
drox
ypro
pyl)
-(2-
hydr
oxye
thyl
) am
ine
N-N
itros
o-N
-met
hyl-
4-u
oroa
nilin
eN
itros
o-N
-met
hyl-
N-(
2-ph
enyl
) eth
ylam
ine
Nitr
oso-
12
36-
tetr
ahyd
ropy
ridi
neN
-Nit
roso
( 22
2-t
riu
oroe
thyl
) eth
ylam
ine
N-N
itros
oall
yl-2
3-d
ihyd
roxy
prop
ylam
ine
N-N
itro
soal
lyl-
2-hy
drox
ypro
pyla
min
eN
-Nit
roso
ally
l-2-
oxop
ropy
lam
ine
Nitr
osoa
myl
uret
han
Nitr
osoa
naba
sine
N-N
itros
obis
( 2-h
ydro
xypr
opyl
) am
ine
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
diet
hyla
min
eN
-Nitr
osod
ipro
pyla
min
eN
itro
soet
hylu
reth
ane
Nit
roso
hept
amet
hyle
neim
ine
N-N
itro
som
ethy
l-2
3-di
hydr
oxyp
ropy
lam
ine
N-N
itros
omet
hyl-
2-hy
drox
ypro
pyla
min
eN
-Nit
roso
met
hyl(
2-ox
opro
pyl)
amin
e2-
Nitr
osom
ethy
lam
inop
yrid
ine
Nit
roso
met
hyla
nili
neN
-Nitr
oson
orni
cotin
e-1-
N-o
xide
N-N
itro
sopi
peri
dine
z N
-Nit
roso
thia
ldin
eN
-Nit
roso
thio
mor
phol
ine
Gal
lbla
dder
Ham
ster
1N
-Met
hyl-
N-f
orm
ylhy
draz
ine
Mou
se4
N-E
thyl
-N-f
orm
ylhy
draz
ine
N-M
ethy
l-N
-for
myl
hydr
azin
e3-
Met
hylb
utan
alm
ethy
lfor
myl
hydr
azon
eN
-N-P
ropy
l-N
-for
myl
hydr
azin
eM
onke
y1
Aa
toxi
nB
y 1H
arde
rian
glan
dM
ouse
19B
enze
nez
Ben
zidi
ne2
HC
l2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
13-
But
adie
nez
Cap
tafo
lz C
hlor
opre
nez
Cup
ferr
onz
Dic
hlor
oace
tyle
nez
Eth
ylen
eox
idez
Gen
tian
viol
etG
lyci
dolz
Iodi
nate
dgl
ycer
olz
Isop
rene
N-M
ethy
lola
cryl
amid
ey N
itro
met
hane
z 4
4-O
xydi
anil
inez
12
3-T
rich
loro
prop
anez
24
6-T
rini
tro-
13-
dim
ethy
l-5-
tert
-but
ylbe
nzen
eV
inyl
uor
idez
Hem
atop
oiet
icM
ouse
53A
ceta
mid
ez A
at
oxin
cru
dez
Ally
liso
vale
rate
z tr
ans-
5-A
min
o-3[
2-( 5
-nitr
o-2-
fury
l)vi
nyl] -
12
4-ox
adia
zole
2-A
min
o-4-
( p-n
itro
phen
yl) t
hiaz
ole
syst
em2-
Am
inoa
nthr
aqui
none
z 5-
Aza
cyti
dine
z A
zath
iopr
ine
Ben
zene
z 1
4-B
enzo
quin
one
Ben
zotr
ichl
orid
eB
enzo
ylhy
draz
ine
13-
But
adie
nez
12-
di-n
-But
ylhy
draz
ine
2HC
lC
apta
folz
Chl
oram
buci
lz C
hlor
inat
edpa
raf
ns( C
234
3ch
lori
ne)y
Cyc
loph
osph
amid
ez D
acar
bazi
nez
DD
Tz
Dib
rom
odul
cito
lz D
ibro
mom
anni
tolz
Est
radi
olm
usta
rdy
Eth
ylen
eox
idez
5-Fl
uoro
urac
ily Fo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z G
entia
nvi
olet
Hex
anam
idey
2-H
ydra
zino
-4-(
p-am
inop
heny
l)th
iazo
lez
2-H
ydra
zino
-4-
( p-n
itro
phen
yl) t
hiaz
olez
1-( 2
-Hyd
roxy
ethy
l)-1
-nit
roso
urea
z IC
RF
-159
z Is
opho
spha
mid
ez Is
opre
neM
eIQ
xz M
elph
alan
z 1-
Met
hyl-
14-
dihy
dro-
7-[ 2
-(5-
nitr
ofur
yl) v
inyl
] -4-
oxo-
18-
naph
thyr
idin
e-3-
carb
oxyl
ate
pota
ssiu
mM
ethy
lmet
hane
sulf
onat
e4
4-M
ethy
lene
dian
ilin
e2H
Clz
Met
roni
dazo
lez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez P
hene
ster
inz
Phe
nolp
htha
lein
z Ph
IPH
Clz
Phor
bol
Proc
arba
zine
HC
lz S
trob
ane
Tetr
auo
roet
hyle
nez
Thi
o-te
paz
p-To
lylu
reay
Tri
s(2-
chlo
roet
hyl)
phos
phat
ez U
reth
anez
CI
vat
yello
w4y
( Con
tinue
don
next
page
)
641
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Mon
key
1P
roca
rbaz
ine
HC
lz
Rat
56A
llyl
isov
aler
atez
1-A
myl
-1-n
itros
oure
aA
traz
iney
Ben
zidi
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
CI
dir
ectb
lue
15
N-n
-But
yl-N
-nitr
osou
rea
Cad
miu
mch
lori
deC
hlor
ambu
cilz
Cyc
loph
osph
amid
ez D
acar
bazi
nez
13-
Dib
utyl
-1-n
itro
sour
eaD
ichl
oroa
cety
lene
z 3
3-D
ichl
orob
enzi
dine
Dic
hlor
vosz
Dim
etho
xane
33
-Dim
etho
xybe
nzid
ine-
44
-dii
socy
anat
ey 3
3-D
imet
hoxy
benz
idin
e2H
Cl
Dim
ethy
lmor
phol
inop
hosp
hora
mid
atey
2-( 2
2-D
imet
hylh
ydra
zino
) -4-
( 5-n
itro-
2-fu
ryl)
thia
zole
Eth
ylen
eox
idez
Form
alde
hyde
z Fo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z F
uran
z G
lyci
dolz
FD
ampC
gree
nno
1y
FDamp
Cgr
een
no2
y H
emat
oxyl
in2
-Hyd
razi
no-4
-(p-
amin
ophe
nyl)
thia
zole
z H
ydro
quin
onez
1-( 2
-Hyd
roxy
ethy
l)-1
-nit
roso
urea
z Io
dina
ted
glyc
erol
z L
asio
carp
ine
2-M
erca
ptob
enzo
thia
zole
y M
etep
aM
ethy
lter
t-bu
tyle
ther
z M
irex
z l-
5-M
orph
olin
omet
hyl-
3-[(
5-ni
trof
urfu
ryli
dene
) am
ino]
-2-o
xazo
lidi
none
H
Cl
Nit
rite
sod
ium
y N
-[5-
( 5-N
itro-
2-fu
ryl)
-13
4-t
hiad
iazo
l-2-
yl] a
ceta
mid
ez o-
Nit
roan
isol
ez 1-
[(5-
Nitr
ofur
fury
liden
e)am
ino]
-2-i
mid
azol
idin
one
1-N
itro
pyre
neN
itros
o-N
-met
hyl-
N-(
2-ph
enyl
) eth
ylam
ine
N-N
itros
odie
than
olam
ine
PhIP
HC
lz P
roca
rbaz
ine
HC
lz P
ropa
nesu
ltone
N-P
ropy
l-N
-nit
roso
urea
FD
ampC
red
no2
FD
ampC
red
no4
y Te
trac
hlor
oeth
ylen
ez Te
tra
uoro
ethy
lene
z T
hio-
tepa
z 2
46-
Tri
chlo
roph
enol
z T
rp-P
-2ac
etat
ez
Kid
ney
Ham
ster
1B
rom
ate
pota
ssiu
mz
Mou
se26
o-B
enzy
l-p-
chlo
roph
enol
y 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bro
mat
epo
tass
ium
z B
rom
odic
hlor
omet
hane
z 1
3-B
utad
iene
z 1
2-di
-n-B
utyl
hydr
azin
e2H
Cl
Caf
feic
acid
z C
hlor
ofor
mz
Chl
orop
rene
z D
amin
ozid
ez 2
4-D
iam
inop
heno
l2H
Cly
Dic
hlor
oace
tyle
nez
24-
Din
itrot
olue
ne( c
onta
inin
g1
0-1
52
6-di
nitr
otol
uene
)zH
ydro
quin
onez
N-H
ydro
xy-2
-ace
tyla
min
ouo
rene
z 3-
Hyd
roxy
-p-b
utyr
ophe
neti
dide
L
ead
acet
ate
basi
cz M
ercu
rym
ethy
lchl
orid
eN
itril
otri
acet
icac
idz
Och
rato
xin
Az
Phe
nace
tinz
CI
pig
men
tred
3z St
rept
ozot
ocin
z T
ris(
2-ch
loro
ethy
l)ph
osph
atez
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez V
inyl
iden
ech
lori
dey
Mon
key
1C
ycas
inan
dm
ethy
lazo
xym
etha
nola
ceta
teR
at86
A
atox
inB
1y 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 1-
Am
ino-
2-m
ethy
lant
hraq
uino
nez
2-A
min
o-5-
( 5-n
itro-
2-fu
ryl)
-13
4-o
xadi
azol
e2-
Am
ino-
5-( 5
-nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
e2-
Am
ino-
4-ni
trop
heno
ly 2-
Am
ino-
5-ni
trot
hiaz
oley
o-A
nisi
dine
HC
lz A
rist
oloc
hic
acid
so
dium
salt
( 77
AA
I21
A
AII
) A
zoxy
met
hane
Bar
bita
lso
dium
Ben
zofu
ranz
Bro
mat
epo
tass
ium
z B
rom
odic
hlor
omet
hane
z te
rt-B
utyl
alco
holz
Caf
feic
acid
z C
apta
folz
Cap
tanz
Chl
orin
ated
para
fns
( C12
60
chlo
rine
)zC
hlor
ofor
mz
3-( p
-Chl
orop
heny
l)-1
1-d
imet
hylu
reay
Chl
orop
rene
z C
hlor
otha
loni
ly C
inna
myl
anth
rani
late
z C
itrin
inC
oum
arin
z D
ichl
oroa
cety
lene
z 1
4-D
ichl
orob
enze
nez
Die
thyl
acet
amid
e3
4-D
ihyd
roco
umar
inz
Dim
etho
xane
Dim
ethy
lmet
hylp
hosp
hona
tey
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
N-4
-(4
-Flu
orob
iphe
nyl)
acet
amid
eFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z G
lyci
neH
exac
hlor
obut
adie
ne
Hex
achl
oroe
than
ez H
exam
ethy
lmel
amin
e2-
Hyd
razi
no-4
-(5-
nitr
o-2-
fury
l)th
iazo
lez
Hyd
roqu
inon
ez 1-
( 2-H
ydro
xyet
hyl)
-1-n
itro
sour
eaz
Isop
horo
ney
Lea
dac
etat
ey L
ead
acet
ate
basi
cz d-
Lim
onen
ey 2-
Met
hoxy
-3-a
min
odib
enzo
fura
n8-
Met
hoxy
psor
alen
Z-M
ethy
l-O
NN
-azo
xyet
hane
Met
hylt
ert-
buty
leth
erz
N-(
N-M
ethy
l-N
-nit
roso
carb
amoy
l)-l
-orn
ithi
nea
-Met
hylb
enzy
lalc
ohol
y M
irex
z l-
5-M
orph
olin
omet
hyl-
3-[(
5-ni
trof
urfu
rylid
ene)
amin
o]-2
-oxa
zolid
inon
eH
Cl
Nit
rilo
tria
ceti
cac
idz
Nit
rilo
tria
cetic
acid
tri
sodi
umsa
ltm
onoh
ydra
tey
3-( 5
-Nitr
o-2-
fury
l)-i
mid
azo(
12-
a) p
yrid
inez
N-[
3-( 5
-Nitr
o-2-
fury
l)-1
24
-oxa
diaz
ole-
5-yl
] -m
ethy
l]ac
etam
ide
N-[
5-( 5
-Nitr
o-2-
fury
l)-1
34
-thi
adia
zol-
2-yl
] ace
tam
idez
o-N
itro
anis
olez
Nitr
oben
zene
z 2-
Nit
ro
uore
ne
1-[(
5-N
itrof
urfu
rylid
ene)
amin
o]hy
dant
oinz
1-N
itro
so-1
-hyd
roxy
ethy
l-3-
chlo
roet
hylu
rea
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
diet
hyla
min
eN
-Nitr
osod
imet
hyla
min
ez N
-Nit
roso
pyrr
olid
inez
Och
rato
xin
Az
CI
aci
dor
ange
3y N
-Oxy
diet
hyle
neth
ioca
rbam
yl-N
-oxy
diet
hyle
nesu
lfen
amid
eP
hena
cetin
z Ph
enaz
one
Phen
olph
thal
einz
Phen
ylbu
tazo
nez
o-Ph
enyl
phen
ate
sodi
umy
Que
rcet
iny
Salic
ylaz
osul
fapy
ridi
nez
Str
epto
zoto
cinz
Tetr
achl
oroe
thyl
enez
Tetr
auo
roet
hyle
nez
Tetr
ahyd
rofu
ranz
12
3-T
rich
loro
prop
anez
Tri
s(2-
chlo
roet
hyl)
phos
phat
ez T
ris(
23-
dibr
omop
ropy
l)ph
osph
atez
Vin
ylch
lori
dez
Lar
gein
test
ine
Ham
ster
51
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
Hyd
razi
nez
Met
hylh
ydra
zine
Ure
than
ezM
ouse
1C
apsa
icin
Rat
32A
at
oxin
B1y
1-A
llyl
-1-n
itros
oure
a1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z A
myl
opec
tin
sulf
ate
Azo
xym
etha
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
te
chni
calg
rade
z C
Id
irec
tblu
e15
Bro
mod
ichl
orom
etha
nez
N-N
-But
yl-n
-nitr
osou
rea
Car
rage
enan
aci
d-de
grad
edC
hrys
azin
z D
extr
ansu
lfat
eso
dium
( DS-
M-1
) 3
3-D
imet
hoxy
benz
idin
e2H
Cl
33
-Dim
ethy
lben
zidi
ne2
HC
lz Z
-Eth
yl-O
NN
-azo
xym
etha
ne1
-Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-t
hiaz
olyl
] hyd
razi
dez
Glu
-P-1
z G
lu-P
-2z
Gly
cido
lz N
-Hex
ylni
tros
oure
a1-
Hyd
roxy
anth
raqu
inon
e1-
( 2-H
ydro
xyet
hyl)
-1-n
itro
sour
eaz
IQz
o-N
itro
anis
olez
N-N
itro
sobi
s(2-
oxop
ropy
l)am
ine
Phe
nazo
pyri
dine
HC
lz P
hIP
HC
lz C
Ia
cid
red
114
44
-Thi
odia
nilin
ez T
ribr
omom
etha
ney
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez
Liv
erD
og2
33
-Dic
hlor
oben
zidi
ne4
4-M
ethy
lene
-bis
( 2-c
hlor
oani
line
)H
amst
er16
2-A
cety
lam
ino
uore
nez
pp
-DD
Ey
12-
Dim
ethy
lhyd
razi
ne2
HC
lH
exac
hlor
oben
zene
z H
ydra
zine
sulf
atez
N-H
ydro
xy-2
-ace
tyla
min
ouo
rene
z N
-Met
hyl-
N-f
orm
ylhy
draz
ine
Met
hylh
ydra
zine
Met
hyln
itros
amin
o-N
N-d
imet
hyle
thyl
amin
eN
-Nitr
oso-
13-
oxaz
olid
ine
Nit
roso
-2-o
xopr
opyl
etha
nola
min
eN
-Nitr
osoa
llyl-
2-ox
opro
pyla
min
eN
-Nit
roso
azet
idin
eN
-Nit
roso
mor
phol
ine
N-N
itros
opip
erid
inez
N-N
itros
opyr
rolid
inez
Mou
se23
1A
-a-C
Ace
tam
inop
henz
2-A
cety
lam
ino
uore
nez
Aci
uor
fen
Ald
rinz
1-A
min
o-2
4-di
brom
oant
hraq
uino
nez
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
1-A
min
o-2-
met
hyla
nthr
aqui
none
z 2-
Am
inoa
nthr
aqui
none
z 4-
Am
inod
iphe
nyl
2-A
min
odip
heny
lene
oxid
e3-
Am
inot
riaz
olez
Ara
mite
z A
rocl
or12
54y
Aur
amin
e-O
z B
enzi
dine
2H
Cl
Ben
zofu
ranz
Ben
zyla
ceta
tey
3-B
enzy
lsyd
none
-4-a
ceta
mid
ez B
is( 2
-chl
oro-
1-m
ethy
leth
yl) e
ther
tec
hnic
algr
adey
Bis
-2-c
hlor
oeth
ylet
her
Bis
-2-h
ydro
xyet
hyld
ithio
carb
amic
acid
pot
assi
umC
Id
irec
tbla
ck38
CI
dir
ectb
lue
218z
HC
blue
no1
z H
Cbl
ueno
1( p
uri
ed)
Bro
mod
ichl
orom
etha
nez
13-
But
adie
nez
But
ylat
edhy
drox
ytol
uene
y 1
1-di
-n-B
utyl
hydr
azin
eC
apta
folz
Car
bazo
le
Car
bon
tetr
achl
orid
ez C
hlor
alhy
drat
eC
hlor
ambe
ny C
hlor
dane
tec
hnic
algr
adey
Chl
oren
dic
acid
z C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
1-
Chl
oro-
2-ni
trob
enze
ney
1-C
hlor
o-4-
nitr
oben
zene
y 4-
Chl
oro-
m-p
heny
lene
diam
inez
4-C
hlor
o-o-
phen
ylen
edia
min
ez 5-
Chl
oro-
o-to
luid
iney
642
[ 4-C
hlor
o-6-
( 23
-xyl
idin
o)-2
-pyr
imid
inyl
thio
] ace
ticac
idz
4-C
hlor
o-6-
( 23
-xyl
idin
o)-2
-pyr
imid
inyl
thio
( N-b
-hyd
roxy
ethy
l)ac
etam
idez
Chl
oroa
ceta
ldeh
yde
p-C
hlor
oani
line
HC
lz C
hlor
oben
zila
tey
Chl
orod
ibro
mom
etha
ney
Chl
orof
orm
z C
hlor
opre
nez
Chr
ysaz
inz
CI-
924
Cin
nam
ylan
thra
nila
tez
Cip
ro
brat
ez C
lobu
zari
ty C
ompo
und
LY17
1883
Cou
mar
inz
p-C
resi
dine
z C
upfe
rron
z C
ycla
mat
eso
dium
y C
yclo
chlo
roti
neC
ypro
tero
neac
etat
ep
p-D
DD
y p
p-D
DE
y D
DT
z D
ialla
te2
4-D
iam
inot
olue
nez
24-
Dia
min
otol
uene
2H
Clz
35-
Dic
hlor
o-( N
-11
-dim
ethy
l-2-
prop
ynyl
) ben
zam
ide
26-
Dic
hlor
o-p-
phen
ylen
edia
min
ey D
ichl
oroa
cetic
acid
z 1
4-D
ichl
orob
enze
nez
12-
Dic
hlor
opro
pane
y D
icof
oly
Die
ldri
nz D
ifta
lone
34
-Dih
ydro
coum
arin
z D
ihyd
rosa
frol
ez 2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 1
1-D
imet
hylh
ydra
zine
y 1
4-D
ioxa
nez
55-
Dip
heny
lhyd
anto
iny
Dip
yron
ey D
oxyl
amin
esu
ccin
atez
Est
rago
led
l-E
thio
nine
z o-
Eth
oxyb
enza
mid
eN
-Eth
yl-N
-for
myl
hydr
azin
eE
thyl
ene
imin
eE
thyl
ene
thio
urea
z 2-
Eth
ylhe
xano
ly di
( 2-E
thyl
hexy
l)ad
ipat
ey di
( 2-E
thyl
hexy
l)ph
thal
atez
4-F
luor
o-4-
amin
odip
heny
lF
uran
z Fu
rfur
alz
Gen
tian
viol
etG
lu-P
-1z
Glu
-P-2
z G
lyci
dolz
Gri
seof
ulvi
nH
CD
Dm
ixtu
rez
Hep
tach
lory
Hex
achl
orob
enze
nez
a-1
23
45
6-H
exac
hlor
ocyc
lohe
xane
z b
-12
34
56
-Hex
achl
oroc
yclo
hexa
nec
-12
34
56
-Hex
achl
oroc
yclo
hexa
ney
Hex
achl
oroc
yclo
hexa
ne
tech
nica
lgra
deH
exac
hlor
oeth
anez
Hex
anal
met
hylf
orm
ylhy
draz
one
Hyd
razi
nesu
lfat
ez H
ydra
zobe
nzen
ez H
ydro
quin
onez
N-H
ydro
xy-2
-ac
etyl
amin
ouo
rene
z 1
-Hyd
roxy
estr
agol
e2-
Hyd
roxy
ethy
lhyd
razi
ne1
-Hyd
roxy
safr
olez
IQz
Ison
iazi
dz Is
opre
neK
epon
ez L
eupe
ptin
Lov
asta
tinL
uteo
skyr
inM
alon
alde
hyde
sod
ium
saltz
MeA
-a-C
acet
atez
MeI
QM
eIQ
xz M
ethi
dath
ion
3-M
etho
xy-4
-am
inoa
zobe
nzen
eM
ethy
lter
t-bu
tyle
ther
z M
ethy
lclo
fena
pate
z N
-Met
hyl-
N-f
orm
ylhy
draz
ine
3-M
ethy
lbut
anal
met
hylf
orm
ylhy
draz
one
44
-Met
hyle
ne-b
is( 2
-chl
oroa
nili
ne)
2HC
ly M
ethy
lene
chlo
ride
z 4
4-M
ethy
lene
bis(
NN
-dim
ethy
l)be
nzen
amin
ez 4
4-M
ethy
lene
dian
iline
2H
Clz
Met
hylh
ydra
zine
N-M
ethy
lola
cryl
amid
ey M
ethy
lphe
nida
teH
Cly
Mic
hler
rsquoske
tone
z M
irex
z 1
5-N
apht
hale
nedi
amin
ez 2-
Nap
hthy
lam
inez
Nit
hiaz
idez
3-N
itro-
p-ac
etop
hene
tidey
5-N
itro-
o-an
isid
inez
2-N
itro
-p-p
heny
lene
diam
iney
5-N
itro
-o-t
olui
dine
y 5-
Nitr
oace
naph
then
ez o-
Nitr
oani
sole
z N
itrob
enze
nez
6-N
itrob
enzi
mid
azol
ey N
itro
fenz
Nit
rom
etha
nez
Nitr
osod
ibut
ylam
inez
N-N
itros
odim
ethy
lam
inez
p-N
itros
odip
heny
lam
inez
N-N
itro
sohe
xam
ethy
lene
imin
eN
-Nit
roso
pipe
ridi
nez
Non
abro
mob
iphe
nyl
Och
rato
xin
Az
Oxa
zepa
my
44
-Oxy
dian
iline
z Pe
ntac
hlor
oeth
aney
Pent
achl
oron
itrob
enze
ney
23
45
6-Pe
ntac
hlor
ophe
nol(
Dow
icid
eE
C-7
)y 2
34
56-
Pen
tach
loro
phen
olt
echn
ical
grad
ez P
enta
nalm
ethy
lfor
myl
hydr
azon
eP
hena
zopy
ridi
neH
Clz
Phe
noba
rbit
aly
Phen
obar
bita
lso
dium
z Ph
enyl
buta
zone
z o-
Phen
ylen
edia
min
e2H
Clz
Pipe
rony
l-bu
toxi
dez
Pipe
rony
lsul
foxi
dey
Poly
brom
inat
edbi
phen
ylm
ixtu
rez
Prob
enec
idy
N-N
-Pro
pyl-
N-f
orm
ylhy
draz
ine
Damp
Cre
dno
5z
Rif
ampi
ciny
Rip
azep
amy
p-R
osan
iline
HC
lz S
afro
lez
Sali
cyla
zosu
lfap
yrid
inez
Sel
eniu
mdi
ethy
ldith
ioca
rbam
ate
Sel
eniu
msu
lde
z S
trob
ane
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
11
12-
Tetr
achl
oroe
than
ey 1
12
2-Te
trac
hlor
oeth
aney
Tetr
achl
oroe
thyl
enez
Tetr
achl
orvi
npho
sy Te
tra
uoro
-m-p
heny
lene
diam
ine
2HC
ly Te
tra
uoro
ethy
lene
z Te
trah
ydro
fura
nz T
hioa
ceta
mid
ez 4
4-T
hiod
iani
linez
Thi
oura
cilz
Tolu
ene
diis
ocya
nate
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
m-T
olui
dine
HC
ly o-
Tolu
idin
eH
Clz
p-To
luid
ine
HC
ly To
xaph
eney
T-2
toxi
nT
riam
tere
ney
Tri
chlo
roac
etic
acid
y 2
46-
Tri
chlo
roan
iline
y 1
12-
Tri
chlo
roet
hane
y T
rich
loro
ethy
lene
z T
rich
loro
ethy
lene
( wit
hout
epic
hlor
ohyd
rin)
y 2
46-
Tri
chlo
roph
enol
z 1
23-
Tri
chlo
ropr
opan
ez T
ri
ural
int
echn
ical
grad
ey 2
45-
Tri
met
hyla
nili
nez
24
5-T
rim
ethy
lani
line
HC
lz 2
46-
Tri
met
hyla
nilin
eH
Clz
24
6-T
rini
tro-
13-
dim
ethy
l-5-
tert
-but
ylbe
nzen
eT
ris(
2-ch
loro
ethy
l)ph
osph
atez
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez T
ris(
2-et
hylh
exyl
) pho
spha
tey
Trp
-P-1
acet
atez
Trp
-P-2
acet
atez
Ure
than
ez V
inyl
carb
amat
eV
inyl
uo
ride
z 2
5-X
ylid
ine
HC
lz C
Id
ispe
rse
yell
ow3z
Zea
rale
none
y
Mon
key
8A
ato
xin
B1y
Cyc
asin
and
met
hyla
zoxy
met
hano
lace
tate
IQ
z N
-Nitr
osod
ieth
ylam
ine
N-N
itro
sodi
prop
ylam
ine
N-N
itro
sopi
peri
dine
z S
teri
gmat
ocys
tinz
Ure
than
ez
Rat
206
Ace
tam
idez
Ace
tam
inop
henz
Ace
toxi
me
2-A
cety
lam
ino
uore
nez
A
atox
icol
A
atox
inB
y 1A
at
oxin
cru
dez
1-A
min
o-2
4-di
brom
oant
hraq
uino
nez
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
1-A
min
o-2-
met
hyla
nthr
aqui
none
z 2-
Am
inoa
nthr
aqui
none
z o-
Am
inoa
zoto
luen
ey 11
-Am
inou
ndec
anoi
cac
idy
Ara
mit
ez A
rocl
or12
60A
uram
ine-
Oz
Azo
xym
etha
neB
emit
radi
ne
Ben
zidi
ne3
-Ben
zyls
ydno
ne-4
-ace
tam
idez
Bis
( 23
-dib
rom
opro
pyl)
phos
phat
em
agne
sium
salt
CI
dir
ectb
lue
15
Bro
mod
ichl
orom
etha
nez
Bud
eson
ide
Cap
tafo
lz C
arbo
nte
trac
hlor
idez
Chl
oren
dic
acid
z C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
4-C
hlor
o-4
-am
inod
iphe
nyle
ther
z 2-
Chl
oro-
5-( 3
5-d
imet
hylp
iper
idin
osul
phon
yl) b
enzo
icac
id[
4-C
hlor
o-6-
( 23
-xy
lidi
no) -
2-py
rim
idin
ylth
io] a
ceti
cac
idz
4-C
hlor
o-6-
( 23
-xyl
idin
o)-2
-pyr
imid
inyl
thio
( N-b
-hyd
roxy
ethy
l)ac
etam
idez
Chl
orob
enze
ney
Chl
orof
orm
z 3-
( p-C
hlor
ophe
nyl)
-11
-dim
ethy
lure
ay C
ipro
bra
tez
Cliv
orin
eC
lob
rate
y C
loph
enA
30C
oum
arin
z p-
Cre
sidi
nez
Cro
tona
ldeh
yde
Cup
ferr
onz
Cyc
lope
ntan
one
oxim
eD
DT
z D
ecab
rom
odip
heny
loxi
dey
Deh
ydro
epia
ndro
ster
one
Deh
ydro
epia
ndro
ster
one
acet
ate
24-
Dia
min
otol
uene
z 2
4-D
iam
inot
olue
ne2
HC
lz 1
2-D
ibro
moe
than
ez D
ichl
oroa
ceti
cac
idz
Dic
hlor
oace
tyle
nez
NN
-Die
thyl
-4-(
4-[
pyri
dyl-
1-o
xide
] azo
) ani
line
Die
thyl
stil
best
rolz
Dim
etho
xane
3
3-D
imet
hoxy
benz
idin
e2H
Cl
56-
Dim
etho
xyst
erig
mat
ocys
tinN
N-D
imet
hyl-
4-am
inoa
zobe
nzen
e6-
Dim
ethy
lam
ino-
44-
diph
enyl
-3-h
epta
nola
ceta
teH
Cly
33
-Dim
ethy
lben
zidi
ne2
HC
lz D
imet
hyln
itram
ine
Din
itros
ohom
opip
eraz
ine
26-
Din
itro
tolu
ene
24-
Din
itrot
olue
ne( c
onta
inin
g1
0-1
52
6-di
nitr
otol
uene
)z
Din
itrot
olue
net
echn
ical
grad
e( 2
4( 7
7) -
and
26
( 19
) -)
14-
Dio
xane
z D
ipen
tyln
itro
sam
ine
Dox
ylam
ine
succ
inat
ez E
thin
yles
trad
iol
Eth
ioni
ne
dl-E
thio
nine
z 4-
Eth
oxy-
phen
ylur
eaE
thyl
alco
holy
Z-E
thyl
-ON
N-a
zoxy
etha
neZ
-Eth
yl-O
NN
-azo
xym
etha
neE
thyl
ene
thio
urea
z di
( 2-E
thyl
hexy
l)ph
thal
atez
Flu
cona
zole
y N
-(2-
Flu
oren
yl) -
22
2-tr
iuo
roac
etam
ide
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-t
hiaz
olyl
] hyd
razi
dez
Fum
onis
inB
1F
uran
z Fu
rfur
alz
Glu
-P-1
z G
lu-P
-2z
FDamp
Cgr
een
no1
y H
CD
Dm
ixtu
rez
Hex
achl
orob
enze
nez
a-1
23
45
6-H
exac
hlor
ocyc
lohe
xane
z H
ydra
zine
z H
ydra
zine
sulf
atez
Hyd
razo
benz
enez
Hyd
roch
loro
uor
ocar
bon
123
N-H
ydro
xy-2
-ace
tyla
min
ouo
rene
z 1-
Hyd
roxy
anth
raqu
inon
e1-
( 2-H
ydro
xyet
hyl)
-nitr
oso-
3-ch
loro
ethy
lure
a1
-Hyd
roxy
safr
olez
IQz
IQH
Cl
Ison
iazi
dz K
epon
ez L
asio
carp
ine
MeA
-a-C
acet
atez
MeI
Qxz
Met
hapy
rile
neH
Cl
Z-M
ethy
l-O
NN
-azo
xyet
hane
Met
hylc
arba
mat
ey M
ethy
lclo
fena
pate
z 3
-Met
hyl-
4-di
met
hyla
min
oazo
benz
ene
2-M
ethy
l-1-
nitr
oant
hraq
uino
nez
4-( 4
-N-M
ethy
l-N
-nit
rosa
min
osty
ryl)
quin
olin
e4
4-M
ethy
lene
-bis
( 2-c
hlor
oani
line
) 4
4-M
ethy
lene
-bis
( 2-m
ethy
lani
line
) 4
4-M
ethy
lene
dian
ilin
e2H
Clz
4-( M
ethy
lnit
rosa
min
o)-1
-(3-
pyri
dyl)
-1-(
buta
none
) M
etro
nida
zole
z M
ichl
errsquos
keto
nez
Mir
exz
Mon
ocro
tali
neN
afen
opin
Nit
rite
sod
ium
y N
itrob
enze
nez
2-N
itro
buta
ne2
-Nit
ro
uore
ne3
-Nit
rope
ntan
eN
-Nitr
oso-
bis-
( 44
4-t
ri
uoro
-N-b
utyl
) am
ine
1-N
itros
o-5
6-di
hydr
oura
cil
N-N
itro
so-2
3-d
ihyd
roxy
prop
ylet
hano
lam
ine
1-N
itros
o-1-
hydr
oxye
thyl
-3-c
hlor
oeth
ylur
ea1
-Nitr
oso-
1-( 2
-hyd
roxy
prop
yl) -
3-ch
loro
ethy
lure
aN
-Nitr
oso-
( 2-h
ydro
xypr
opyl
) -( 2
-hyd
roxy
ethy
l)am
ine
N-N
itros
o-N
-met
hyl-
N-d
odec
ylam
ine
Nit
roso
-N-m
ethy
l-N
-(2-
phen
yl) e
thyl
amin
e
( Con
tinue
don
next
page
)
643
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
N-N
itro
so-N
-met
hyld
ecyl
amin
e3-
Nit
roso
-2-o
xazo
lidin
one
Nit
roso
-2-o
xopr
opyl
etha
nola
min
eN
itro
so-1
23
6-t
etra
hydr
opyr
idin
eN
-Nit
roso
ally
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itro
soal
lyl-
2-ox
opro
pyla
min
eN
-Nitr
osoa
llyl
etha
nola
min
eN
-Nit
roso
bis(
2-ox
opro
pyl)
amin
eN
itro
sodi
buty
lam
inez
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
diet
hyla
min
eN
-Nitr
osod
imet
hyla
min
ez p-
Nitr
osod
iphe
nyla
min
ez N
-Nit
roso
dipr
opyl
amin
eN
itros
odod
ecam
ethy
lene
imin
eN
-Nit
roso
ephe
drin
eN
itro
soet
hylm
ethy
lam
ine
Nitr
osoh
epta
met
hyle
neim
ine
N-N
itros
omet
hyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nit
roso
met
hyl-
( 2-h
ydro
xyet
hyl)
amin
eN
-Nitr
osom
ethy
l-( 3
-hyd
roxy
prop
yl) a
min
eN
-Nitr
osom
ethy
l(2-
oxop
ropy
l)am
ine
N-N
itro
som
ethy
l-( 2
-tos
ylox
yeth
yl) a
min
eN
itro
som
ethy
lund
ecyl
amin
eN
-Nit
roso
mor
phol
ine
N-N
itros
opip
erid
inez
N-N
itro
sopy
rrol
idin
ez N
-Nit
roso
thia
ldin
eo-
Nit
roso
tolu
ene
Nor
lest
rinz
N-(
9-O
xo-2
-uo
reny
l)ac
etam
ide
44
-Oxy
dian
iline
z 2
34
56-
Pent
achl
orop
heno
lte
chni
calg
rade
z P
etas
iten
ine
Phe
noba
rbit
als
odiu
mz
1-P
heny
lazo
-2-n
apht
holy
o-P
heny
lene
diam
ine
2HC
lz P
iper
onyl
buto
xide
z P
olyb
rom
inat
edbi
phen
ylm
ixtu
rez
Pre
dnis
olon
eP
yril
amin
em
alea
tey
CI
aci
dre
d11
4C
Ip
igm
entr
ed3z
Damp
Cre
dno
5z
Damp
Cre
dno
9y
FD
ampC
red
no1
p-
Ros
anili
neH
Clz
Saf
role
z Se
leni
umsu
lde
z Se
nkir
kine
Ste
rigm
atoc
ystin
z S
ymph
ytin
eTa
mox
ifen
citr
atez
Telo
neII
tec
hnic
algr
adez
33
44
-Te
traa
min
obip
heny
l4H
Clz
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tetr
auo
roet
hyle
nez
Thi
oace
tam
idez
44
-Thi
odia
nilin
ez To
luen
edi
isoc
yana
te
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
Tri
amci
nolo
neac
eton
ide
24
5-T
rim
ethy
lani
line
z 2
45-
Tri
met
hyla
nili
neH
Clz
24
6-T
rim
ethy
lani
line
HC
lz T
rini
trog
lyce
rin
Trp
-P-1
acet
atez
Trp
-P-2
acet
atez
Vin
ylac
etat
ez V
inyl
brom
ide
Vin
ylch
lori
dez
Vin
yl
uori
dez
CI
dis
pers
eye
llow
3z
Tre
esh
rew
1A
ato
xin
B1y
Lun
gH
amst
er3
Met
hyln
itro
sam
ino-
NN
-dim
ethy
leth
ylam
ine
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
1-N
itro
so-3
45
-tri
met
hylp
iper
azin
eM
ouse
116
Ace
tald
ehyd
em
ethy
lfor
myl
hydr
azon
eN
-Ace
tyl-
4-( h
ydro
xym
ethy
l)ph
enyl
hydr
azin
e1-
Ace
tyl-
2-is
onic
otin
oylh
ydra
zine
A
llyl
hydr
azin
eH
Cl
1-A
min
o-2
4-di
brom
oant
hraq
uino
nez
Are
coli
neH
Cl
5-A
zacy
tidi
nez
Ben
zene
z B
enzo
fura
nz B
enzo
tric
hlor
ide
Ben
zoyl
hydr
azin
eB
enzy
lhyd
razi
ne2
HC
l2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bis
( 2-c
hlor
o-1-
met
hyle
thyl
) eth
er
tech
nica
lgra
dey
Bis
-(ch
loro
met
hyl)
ethe
rz 1
3-B
utad
iene
z N
-n-B
utyl
-N-f
orm
ylhy
draz
ine
But
ylat
edhy
drox
ytol
uene
y 1
1-di
-n-B
utyl
hydr
azin
en-
But
ylhy
draz
ine
HC
l1
2-di
-N-B
utyl
hydr
azin
e2H
Cl
Caf
feic
acid
z C
arba
myl
hydr
azin
eH
Cl
1-C
arba
myl
-2-p
heny
lhyd
razi
neC
hlor
ambu
cilz
Chl
orop
rene
z C
obal
tsul
fate
hept
ahyd
rate
z C
oum
arin
z C
yclo
phos
pham
idez
Dac
arba
zine
z D
amin
ozid
ez p
p-D
DD
y D
DT
z 1
1-D
iall
ylhy
draz
ine
12-
Dia
llyl
hydr
azin
e2H
Cl
Dib
enz(
ah)
anth
race
ne1
2-D
ibro
mo-
3-ch
loro
prop
anez
Dib
rom
odul
cito
lz 1
2-D
ibro
moe
than
ez D
ibro
mom
anni
tolz
12-
Dic
hlor
oeth
anez
12-
Dif
orm
ylhy
draz
ine
Dih
ydro
safr
olez
25-
Dim
etho
xy-4
-am
inos
tilbe
nez
33
-Dim
ethy
lben
zidi
ne2
HC
lz 1
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
a-E
cdys
one
Est
radi
olm
usta
rdy
N-E
thyl
-N-f
orm
ylhy
draz
ine
Eth
ylen
eim
ine
Eth
ylen
eox
idez
Eth
ylhy
draz
ine
HC
l5-
Flu
orou
raci
ly Fo
rmyl
hydr
azin
eG
lyci
dolz
c-1
23
45
6-H
exac
hlor
ocyc
lohe
xane
y H
exan
alm
ethy
lfor
myl
hydr
azon
eH
ydra
zine
z H
ydra
zine
sulf
atez
IQz
Isob
utyl
nitr
itez
Ison
iazi
dz Is
onic
otin
icac
idva
nilly
liden
ehyd
razi
de
Isop
rene
Lov
asta
tinM
eIQ
xz M
elph
alan
z 1-
Met
hyl-
14-
dihy
dro-
7-[ 2
-(5-
nitr
ofur
yl) v
inyl
] -4-
oxo-
18-
naph
thyr
idin
e-3-
carb
oxyl
ate
pota
ssiu
m
N-M
ethy
l-N
-for
myl
hydr
azin
eM
ethy
lmet
hane
sulf
onat
e3-
Met
hylb
utan
alm
ethy
lfor
myl
hydr
azon
eM
ethy
lene
chlo
ride
z M
ethy
lhyd
razi
ne
Met
hylh
ydra
zine
sulf
ate
( N-6
) -( M
ethy
lnit
roso
) ade
nine
(N
-6) -
( Met
hyln
itro
so) a
deno
sine
N-M
ethy
lola
cryl
amid
ey M
etro
nida
zole
z M
olyb
denu
mtr
ioxi
dey
Mon
oace
tylh
ydra
zine
Nap
htha
lene
15
-Nap
htha
lene
diam
inez
Nic
otin
icac
idhy
draz
ide
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez 3-
Nitr
o-3-
hexe
nez
Nit
robe
nzen
ez N
itrom
etha
nez
Nit
roso
dibu
tyla
min
ez N
-Nit
roso
dim
ethy
lam
inez
N-N
itros
ohex
amet
hyle
neim
ine
N-N
itro
sopi
peri
dine
z O
zone
y Pe
ntan
alm
ethy
lfor
myl
hydr
azon
en-
Pen
tylh
ydra
zine
HC
lPh
enes
teri
nz Ph
enyl
ethy
lhyd
razi
nesu
lfat
eP
roca
rbaz
ine
HC
lz N
-N-P
ropy
l-N
-for
myl
hydr
azin
eP
ropy
lhyd
razi
neH
Cl
Sel
eniu
msu
lde
z S
trep
tozo
toci
nz Su
lfal
late
z Te
lone
IIt
echn
ical
grad
ez 3
34
4-T
etra
amin
obip
heny
l4H
Clz
Tetr
anitr
omet
hane
z T-
2to
xin
Tri
chlo
roet
hyle
nez
Tri
ura
lint
echn
ical
grad
ey 2
45-
Tri
met
hyla
nilin
eH
Clz
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez U
reth
anez
Vin
ylch
lori
dez
Vin
ylu
orid
ez V
inyl
iden
ech
lori
dey
24-
Xyl
idin
eH
Cly
Mon
key
1U
reth
anez
Rat
551-
Ally
l-1-
nitr
osou
rea
2-A
min
o-5-
( 5-n
itro
-2-f
uryl
) -1
34-
oxad
iazo
le2
-Am
ino-
5-( 5
-nitr
o-2-
fury
l)-1
34
-thi
adia
zole
2-A
min
o-5-
nitr
othi
azol
ey 1-
Am
yl-1
-nitr
osou
rea
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
is-(
chlo
rom
ethy
l)et
herz
HC
blue
no1
z B
rom
oeth
anez
N-n
-But
yl-N
-nit
roso
urea
Cad
miu
mch
lori
deC
adm
ium
sulp
hate
( 11
) 1-
Chl
oroe
thyl
nitr
oso-
3-( 2
-hyd
roxy
prop
yl) u
rea
Chl
orop
rene
z C
obal
tsul
fate
hept
ahyd
rate
z 1
2-D
ibro
moe
than
ez D
imet
hylh
ydro
gen
phos
phit
ey tr
ans-
2-[(
Dim
ethy
lam
ino)
met
hylim
ino]
-5-
[ 2-(
5-ni
tro-
2-fu
ryl)
viny
l] -1
34-
oxad
iazo
le3
3-D
imet
hylb
enzi
dine
2H
Clz
12-
Epo
xybu
tane
y 1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
N-H
exyl
nitr
osou
rea
Hyd
razi
nez
Hyd
razi
nesu
lfat
ez 1-
( 2-H
ydro
xyet
hyl)
-1-n
itro
sour
eaz
Isob
utyl
nitr
itez
Ison
iazi
dz 4
4-M
ethy
lene
-bi
s(2-
chlo
roan
iline
) 4-
( Met
hyln
itros
amin
o)-1
-(3-
pyri
dyl)
-1-b
utan
ol4
-(M
ethy
lnit
rosa
min
o)-1
-(3-
pyri
dyl)
-1-(
buta
none
) N
-[ 3
-(5-
Nitr
o-2-
fury
l)-
12
4-ox
adia
zole
-5-y
l] -m
ethy
lace
tam
ide
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
3-N
itro-
3-he
xene
z 5-
Nitr
oace
naph
then
ez N
-Nit
roso
-bis
-(4
44-
tri
uoro
-N-b
utyl
) am
ine
N-N
itros
o-N
-met
hyl-
N-d
odec
ylam
ine
N-N
itros
o-N
-met
hyl-
N-t
etra
decy
lam
ine
N-N
itro
so-N
-met
hyld
ecyl
amin
eN
-Nitr
oso-
N-m
ethy
lure
az N
-Nitr
osob
is( 2
-hyd
roxy
prop
yl)
amin
eN
-Nitr
osob
is-2
3-d
ihyd
roxy
prop
ylam
ine
( 2-o
xopr
opyl
) am
ine
Nitr
osod
ibut
ylam
inez
N-N
itros
odim
ethy
lam
inez
N-N
itro
soep
hedr
ine
Nitr
osoe
thyl
met
hyla
min
eN
-Nit
roso
met
hyl
N-N
itro
som
ethy
l-( 3
-hyd
roxy
prop
yl) a
min
eN
itro
som
ethy
lund
ecyl
amin
eC
Ia
cid
red
114
Sod
ium
dich
rom
ate
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tetr
anit
rom
etha
nez
24
5-T
rim
ethy
lani
line
z 2
46-
Tri
met
hyla
nili
neH
Clz
Vin
ylch
lori
dez
Mam
mar
ygl
and
Dog
1Ly
nest
reno
lH
amst
er1
Vin
ylch
lori
dez
Mou
se24
5-A
zacy
tidin
ez B
enze
nez
CI
dir
ectb
lack
381
3-B
utad
iene
z C
alci
fero
lC
hlor
opre
nez
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
Die
thyl
stilb
estr
olz
a-E
cdys
one
Est
radi
olE
thyl
ene
oxid
ez F
uros
emid
ey G
lyci
dolz
Gri
seof
ulvi
nIs
onia
zidz
Ison
icot
inic
acid
vani
llylid
eneh
ydra
zide
( N
-6) -
( Met
hyln
itros
o)ad
enos
ine
Nitr
oben
zene
z R
eser
pine
z Su
lfal
late
z V
inyl
chlo
ride
z V
inyl
uor
idez
Vin
ylid
ene
chlo
ride
y
644
Rat
102
4-A
cety
lam
inob
iphe
nyl
2-A
cety
lam
ino
uore
nez
Acr
onyc
ine
Acr
ylam
ide
Acr
ylon
itri
leA
F-2
z 1-
Ally
l-1-
nitr
osou
rea
2-A
min
o-5-
( 5-n
itro-
2-fu
ryl)
-13
4-
oxad
iazo
le2
-Am
ino-
5-( 5
-nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
e2-
Am
ino-
5-ni
trot
hiaz
oley
4-A
min
odip
heny
lHC
l1-
Am
yl-1
-nit
roso
urea
Atr
azin
ey B
emit
radi
ne
Ben
zidi
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
4-B
is( 2
-hyd
roxy
ethy
l)am
ino-
2-( 5
-nit
ro-2
-thi
enyl
) qui
nazo
line
13-
But
adie
nez
N-n
-But
yl-N
-nitr
osou
rea
Cap
tafo
lz C
arbo
nte
trac
hlor
idez
Car
boxy
met
hyln
itros
oure
aC
hlor
ambu
cilz
Chl
orop
rene
z C
ytem
bena
y D
acar
bazi
nez
N-1
-Dia
ceta
mid
ouo
rene
46
-Dia
min
o-2-
( 5-n
itro-
2-fu
ryl)
-S-t
riaz
ine
24-
Dia
min
oani
sole
sulf
atez
24-
Dia
min
otol
uene
z 1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dib
rom
oman
nito
lz 1
3-D
ibut
yl-1
-nit
roso
urea
33
-Dic
hlor
oben
zidi
ne1
2-D
ichl
oroe
than
ez 3
3-D
imet
hoxy
benz
idin
e2H
Cl
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
12-
Dim
ethy
l-5-
nitr
oim
idaz
ole
tran
s-2-
[(D
imet
hyla
min
o)m
ethy
limin
o]-5
-[2-
( 5-n
itro
-2-f
uryl
) vin
yl] -
13
4-ox
adia
zole
Dim
ethy
lam
inoe
thyl
nitr
osoe
thyl
urea
nitr
ite
salt
33
-Dim
ethy
lben
zidi
ne2
HC
lz 2-
( 22
-Dim
ethy
lhyd
razi
no) -
4-( 5
-nitr
o-2-
fury
l)th
iazo
le
24-
Din
itro
tolu
ene
( con
tain
ing
10-
15
24-
Dio
xane
z 1-
Eth
ylni
tros
o-3-
( 2-h
ydro
xyet
hyl)
-ure
a1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
6-di
nitr
otol
uene
)zN
-(2-
Fluo
reny
l)-2
22
-tri
uo
roac
etam
ide
Form
icac
id2-
( 4-m
ethy
l-2-
thia
zoly
l)hy
draz
ide
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-
thia
zoly
l] hyd
razi
dez
Gly
cido
lz H
exam
ethy
lmel
amin
eN
-Hex
ylni
tros
oure
a2-
Hyd
razi
no-4
-(p-
amin
ophe
nyl)
thia
zole
z 2-
Hyd
razi
no-4
-( 5
-nit
ro-2
-fur
yl) t
hiaz
olez
2-H
ydra
zino
-4-(
p-ni
trop
heny
l)th
iazo
lez
Hyd
razo
benz
enez
1-( 2
-Hyd
roxy
ethy
l)-3
-[( 5
-nit
rofu
rfur
ylid
ene)
amin
o]-2
-im
idaz
olid
inon
e1-
( 2-H
ydro
xyet
hyl)
-nit
roso
-3-e
thyl
urea
1-(
2-H
ydro
xyet
hyl)
-1-n
itros
oure
az In
dom
etha
cin
IQz
IQH
Cl
Ison
iazi
dz 2-
Met
hoxy
-3-a
min
odib
enzo
fura
n4-
Met
hyl-
1-[(
5-ni
trof
urfu
rylid
ene)
amin
o]-2
-im
idaz
olid
inon
eN
-(N
-Met
hyl-
N-n
itro
soca
rbam
oyl)
-l-o
rnit
hine
3-M
ethy
lcho
lant
hren
e4
4-M
ethy
lene
-bi
s(2-
chlo
roan
iline
) 4
4-M
ethy
lene
-bis
( 2-m
ethy
lani
line)
Met
hyle
nech
lori
dez
Met
roni
dazo
lez
l-5-
Mor
phol
inom
ethy
l-3-
[(5-
nitr
ofur
fury
lide
ne) a
min
o]-
2-ox
azol
idin
one
HC
lN
ithia
zide
z 5-
Nitr
o-2-
fura
ldeh
yde
sem
icar
bazo
nez
3-( 5
-Nitr
o-2-
fury
l)-i
mid
azo(
12-
a)
pyri
dine
z 4-
( 5-N
itro-
2-fu
ryl)
thia
zole
N
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] ace
tam
ide
NN
-[6-
( 5-N
itro
-2-f
uryl
) -S-
tria
zine
-24
-diy
l] bis
acet
amid
e5-
Nitr
oace
naph
then
ez 1-
[(5-
Nit
rofu
rfur
ylid
ene)
amin
o]-2
-im
idaz
olid
inon
eN
itrom
etha
nez
1-N
itrop
yren
eN
orle
stri
nz O
chra
toxi
nA
z N
-(9-
Oxo
-2-
uore
nyl)
acet
amid
ePh
enac
etin
z Ph
enes
teri
nz Ph
IPH
Clz
Proc
arba
zine
HC
lz Pr
opan
esu
lton
e1
2-Pr
opyl
ene
oxid
ez St
yren
ey Su
lfal
late
z 4
4-S
ulfo
nylb
isac
etan
ilid
eTo
luen
edi
isoc
yana
te
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
o-T
olui
dine
HC
lz 1
23-
Tri
chlo
ropr
opan
ez 2
22-
Tri
uor
o-N
-[4-
( 5-n
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] ace
tam
idez
Trp
-P-2
acet
atez
Vin
ylch
lori
dez
FD
ampC
viol
etno
1y
Mes
ovar
ium
Rat
2Sa
lbut
amol
Ter
buta
line
Myo
card
ium
Mou
se2
Est
radi
olm
usta
rdy
Phen
este
rinz
Nas
alca
vity
bB
ush
baby
1N
-Nitr
osod
ieth
ylam
ine
Ham
ster
11A
ceta
ldeh
yde
Dia
llyln
itros
amin
eD
imet
hylc
arba
myl
chlo
ride
Hyd
razi
nez
Met
hyln
itro
sam
ino-
NN
-dim
ethy
leth
ylam
ine
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
N-N
itro
soal
lyl-
2-ox
opro
pyla
min
eN
-Nitr
osom
ethy
l-2
3-di
hydr
oxyp
ropy
lam
ine
N-N
itros
omor
phol
ine
N-N
itros
onor
nico
tine
N-N
itros
opip
erid
inez
Mou
se6
Ally
lgly
cidy
leth
ery
12-
Dib
rom
o-3-
chlo
ropr
opan
ez 1
2-D
ibro
moe
than
ez Fo
rmal
dehy
dez
N-N
itro
sohe
xam
ethy
lene
imin
e1
2-Pr
opyl
ene
oxid
ez
Rat
43A
ceta
ldeh
yde
Acr
ylon
itril
e1-
Azo
xypr
opan
eB
enze
nez
Bis
-(ch
loro
met
hyl)
ethe
rz p-
Cre
sidi
nez
Dia
llyln
itros
amin
e1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dim
ethy
lnitr
amin
eD
imet
hylv
inyl
chlo
ride
z D
initr
osoh
omop
iper
azin
e1
4-D
ioxa
nez
12-
Epo
xybu
tane
y Z
-Eth
yl-O
NN
-azo
xyet
hane
E
thyl
benz
ene
Eth
ylni
tros
ocya
nam
ide
Form
alde
hyde
z H
exam
ethy
lpho
spho
ram
ide
Hyd
razi
nez
N-N
itro
so-N
-met
hyld
ecyl
amin
edi
( N-N
itro
so) -
perh
ydro
pyri
mid
ine
N-N
itros
o(2
22-
tri
uoro
ethy
l)et
hyla
min
e1-
Nitr
oso-
34
5-tr
imet
hylp
iper
azin
eN
-Nitr
osoa
llyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nit
roso
ally
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itro
soal
lyle
than
olam
ine
N-N
itros
obis
( 2-h
ydro
xypr
opyl
) am
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
dipr
opyl
amin
eN
itros
oeth
ylm
ethy
lam
ine
N-N
itros
omet
hyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nitr
osom
ethy
l-( 2
-hyd
roxy
ethy
l)am
ine
N-N
itro
som
ethy
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itros
omet
hyl(
2-ox
opro
pyl)
amin
eN
-Nit
roso
norn
icot
ine-
1-N
-oxi
de
N-N
itro
sopi
peri
dine
z P
hena
cetin
z Ph
enyl
glyc
idyl
ethe
r1
2-Pr
opyl
ene
oxid
ez V
inyl
acet
atez
Vin
ylch
lori
dez
Ner
vous
Mou
se3
13-
But
adie
nez
N-N
itros
odim
ethy
lam
inez
Pro
carb
azin
eH
Clz
syst
emR
at21
Acr
ylam
ide
Acr
ylon
itril
eB
rom
oeth
anez
Chl
oram
buci
lz 1-
( 4-C
hlor
ophe
nyl)
-1-p
heny
l-2-
prop
ynyl
carb
amat
eC
yclo
phos
pham
idez
1-E
thyl
-1-n
itros
oure
aE
thyl
eneo
xide
z 1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
eaG
lu-P
-1z
Glu
-P-2
z G
lyci
dolz
R(
) -2-
Met
hyl-
N-n
itro
sopi
peri
dine
S(
) -2-
Met
hyl-
N-n
itro
sopi
peri
dine
M
ethy
lnit
ram
ine
N-N
itros
o-N
-met
hylu
reaz
N-N
itros
odie
than
olam
ine
1-P
heny
l-3
3-di
met
hyltr
iaze
neP
roca
rbaz
ine
HC
lz P
ropa
nesu
ltone
Vin
ylch
lori
dez
Ora
lcav
ityc
Ham
ster
4A
ceta
ldeh
yde
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
N-N
itros
omor
phol
ine
N-N
itro
sopi
peri
dine
z
Mou
se3
N-N
itros
ohex
amet
hyle
neim
ine
12
3-T
rich
loro
prop
anez
Vin
ylac
etat
ez
Rat
32A
cryl
amid
eA
cryl
onitr
ile
Ben
zene
z 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
CI
dir
ectb
lue
15C
Id
irec
tblu
e21
8z C
hlor
opre
nez
3-D
iazo
tyra
min
eH
Cl
12-
Dib
rom
o-3-
chlo
ropr
opan
ez 3
3-D
imet
hoxy
benz
idin
e2H
Cl
33
-Dim
ethy
lben
zidi
ne2
HC
lz D
imet
hylv
inyl
chlo
ride
z D
initr
osoh
omop
iper
azin
eG
lyci
dolz
IQz
MeA
-a-C
acet
atez
N-N
itros
o-2
3-di
hydr
oxyp
ropy
l-2-
hydr
oxyp
ropy
lam
ine
Nit
roso
-23
-dih
ydro
xypr
opyl
-2-
oxop
ropy
lam
ine
Nitr
oso-
N-m
ethy
l-N
-(2-
phen
yl) e
thyl
amin
eN
itro
soam
ylur
etha
nN
-Nitr
osod
ieth
ylam
ine
Nit
roso
ethy
lure
than
N
itros
ohep
tam
ethy
lene
imin
e1-
Nitr
osoh
ydan
toin
N-N
itros
omet
hyl(
2-ox
opro
pyl)
amin
eN
-Nit
roso
thia
ldin
eN
-Nitr
osot
hiom
orph
olin
eC
Ia
cid
red
114
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tolu
eney
12
3-T
rich
loro
prop
anez
Xyl
ene
mix
ture
( m-x
ylen
eo-
xyle
nep
-xyl
ene)
Ova
ryM
ouse
10B
enze
nez
13-
But
adie
nez
Die
thyl
stil
best
rolz
N-M
ethy
lola
cryl
amid
ey 5-
Nitr
o-2-
fura
ldeh
yde
sem
icar
bazo
nez
5-N
itroa
cena
phth
enez
1-[(
5-N
itro
furf
uryl
iden
e)am
ino]
hyda
ntoi
nz P
heno
lpht
hale
inz
Tam
oxif
enci
trat
ez 4-
Vin
ylcy
cloh
exen
ePa
ncre
asH
amst
er3
Nitr
oso-
23-
dihy
drox
ypro
pyl-
2-ox
opro
pyla
min
eN
itro
so-2
6-d
imet
hylm
orph
olin
eN
itro
so-2
-oxo
prop
ylet
hano
lam
ine
Mon
key
1U
reth
anez
Rat
222-
Am
ino-
5-ni
trop
heno
ly 1-
( Am
inom
ethy
l)cy
cloh
exan
eace
ticac
idA
zase
rine
But
ylbe
nzyl
phth
alat
ey C
hlor
endi
cac
idz
Cin
nam
ylan
thra
nila
tez
Clo
bra
tey
Dic
hlor
vosz
Eth
ylal
coho
ly H
ydro
chlo
ro
uoro
carb
on12
3IQ
HC
lM
alon
alde
hyde
sod
ium
saltz
MeA
-a-C
acet
atez
2-M
erca
ptob
enzo
thia
zole
y M
ethy
lclo
fena
pate
z N
-(N
-Met
hyl-
N-n
itros
ocar
bam
oyl)
-l-o
rnit
hine
4-(
Met
hyln
itro
sam
ino)
-1-(
3-py
ridy
l)-1
-but
anol
4-(
Met
hyln
itros
amin
o)-1
-( 3
-pyr
idyl
) -1-
( but
anon
e)N
afen
opin
Nitr
ofen
z To
luen
edi
isoc
yana
tec
omm
erci
algr
ade
( 24
( 80
) -an
d2
6( 2
0) -
)z1
23
-Tri
chlo
ropr
opan
ez
Peri
tone
alM
ouse
8B
is-1
2-(
chlo
rom
etho
xy) e
than
eB
is-1
4-(
chlo
rom
etho
xy) -
p-xy
lene
Bis
-(ch
loro
met
hyl)
ethe
rz C
hlor
opre
nez
tran
s-1
4-D
ichl
orob
uten
e-2
cavi
tyD
imet
hylc
arba
myl
chlo
ride
Phe
noxy
benz
amin
eH
Clz
Tri
s-1
23-
( chl
orom
etho
xy) p
ropa
neR
at22
Acr
onyc
ine
Acr
ylam
ide
Act
inom
ycin
DA
nili
neH
Cly
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
rom
ate
pota
ssiu
mz
Chl
oroz
otoc
in
Cyt
embe
nay
Dap
sone
y 1
2-D
ibro
moe
than
ez D
ibro
mom
anni
tolz
33
-Dim
ethy
lben
zidi
ne2
HC
lz 1
4-D
ioxa
nez
Eth
ylen
eox
idez
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Gly
cido
lz M
elph
alan
z N
-Met
hyl-
N4
-din
itros
oani
line
Mit
omyc
in-C
N-N
itro
so-2
24
-tri
met
hyl-
12-
dihy
droq
uino
line
poly
mer
Ph
enox
yben
zam
ine
HC
lz o-
Tolu
idin
eH
Clz
( Con
tinue
don
next
page
)
645
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Pitu
itar
ygl
and
Mou
se8
Die
thyl
stil
best
rolz
Eno
vid
Eth
ylen
eth
iour
eaz
Iodi
nate
dgl
ycer
olz
Isop
rene
Nor
lest
rinz
Pro
pylt
hiou
raci
lz Z
eara
leno
ney
Rat
73-
Am
inot
riaz
olez
12-
Dib
rom
oeth
anez
Die
thyl
stil
best
rolz
Eth
ylal
coho
ly 2-
Mer
capt
oben
zoth
iazo
ley
Met
roni
dazo
lez
Nor
lest
rinz
Pros
tate
Rat
4C
adm
ium
chlo
ride
N-N
itros
obis
( 2-h
ydro
xypr
opyl
) am
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
PhIP
HC
lz
Skin
Ham
ster
2U
reth
anez
Vin
ylch
lori
dez
Mou
se5
5-A
zacy
tidin
ez 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Chl
orop
rene
z G
lyci
dolz
Thi
o-te
paz
Rat
332-
Ace
tyla
min
ouo
rene
z 3-
Am
ino-
9-et
hylc
arba
zole
mix
ture
z 1-
Azo
xypr
opan
e2-
Azo
xypr
opan
eB
enze
nez
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
ol
tech
nica
lgra
dez
CI
dir
ectb
lue
15C
arbo
xym
ethy
lnitr
osou
rea
24-
Dia
min
oani
sole
sulf
atez
Dib
rom
odul
cito
lz D
ibro
mom
anni
tolz
Dim
etho
xane
2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 3
3-D
imet
hoxy
benz
idin
e-4
4-d
iisoc
yana
tey
33
-Dim
etho
xybe
nzid
ine
2HC
l3
3-D
imet
hylb
enzi
dine
2H
Clz
Dim
ethy
lvin
ylch
lori
dez
24-
Din
itro
tolu
ene
( con
tain
ing
10-
15
26-
dini
trot
olue
ne)z
1-E
thyl
nitr
oso-
3-( 2
-hyd
roxy
ethy
l)-u
rea
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Gly
cido
lz 1-
( 2-H
ydro
xyet
hyl)
-nit
roso
-3-e
thyl
urea
IQ
z L
asio
carp
ine
MeI
Qxz
N-(
N-M
ethy
l-N
-nitr
osoc
arba
moy
l)-l
-orn
ithi
ne
5-N
itro-
o-an
isid
inez
CI
aci
dre
d11
4p-
Ros
anili
neH
Clz
Thi
o-te
paz
Thi
oure
ay V
inyl
chlo
ride
z F
Damp
Cvi
olet
no1
y
Smal
lint
esti
neM
ouse
6C
apta
folz
Cap
tanz
N-E
thyl
-N-n
itro
-N-n
itro
sogu
anid
ine
Hyd
roge
npe
roxi
deN
-Met
hyl-
N-n
itro-
N-n
itros
ogua
nidi
nez
N-(
Tri
chlo
rom
ethy
lthi
o)ph
thal
imid
eM
onke
y1
Ure
than
ez
Rat
29A
cryl
onitr
ile
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
is( 2
3-d
ibro
mop
ropy
l)ph
osph
ate
mag
nesi
umsa
lt4
-Bis
( 2-h
ydro
xyet
hyl)
amin
o-2-
( 5-n
itro
-2-t
hien
yl) q
uina
zolin
eC
Id
irec
tblu
e15
Car
boxy
met
hyln
itros
oure
a1-
( 4-C
hlor
ophe
nyl)
-1-p
heny
l-2-
prop
ynyl
carb
amat
e2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 3
3-D
imet
hoxy
benz
idin
e2H
Cl
46-
Dim
ethy
l-2-
( 5-n
itro
-2-f
uryl
)py
rim
idin
etr
ans-
2-[(
Dim
ethy
lam
ino)
met
hylim
ino]
-5-[
2-( 5
-nit
ro-2
-fur
yl) v
inyl
] -1
34-
oxad
iazo
le3
3-D
imet
hylb
enzi
dine
2H
Clz
Z-E
thyl
-ON
N-a
zoxy
met
hane
1-E
thyl
-1-n
itros
oure
aFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z G
lu-P
-1z
Glu
-P-2
z IQ
z L
asio
carp
ine
N-M
ethy
l-N
-nitr
o-N
-nitr
osog
uani
dine
z N
-[5-
( 5-N
itro-
2-fu
ryl)
-13
4-t
hiad
iazo
l-2-
yl] a
ceta
mid
ez N
-Nitr
oso-
N-i
sobu
tylu
rea
3-N
itro
so-2
-oxa
zoli
dino
neN
itro
soet
hylu
reth
ane
PhI
PH
Clz
Pro
pane
sulto
neQ
uerc
etin
y C
Ia
cid
red
114
Trp
-P-2
acet
atez
Sple
enR
at7
Ani
line
HC
ly A
zobe
nzen
ey p-
Chl
oroa
nili
neH
Clz
Dap
sone
y o-
Nitr
osot
olue
neD
ampC
red
no9
y o-
Tolu
idin
eH
Clz
Stom
ach
Ham
ster
18A
F-2z
14-
Din
itros
o-2
6-di
met
hylp
iper
azin
eFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z H
ydra
zine
z N
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
N-[
4-( 5
-Nitr
o-2-
fury
l)-2
-thi
azol
yl] a
ceta
mid
eN
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] for
mam
idez
N-N
itro
so-2
3-d
ihyd
roxy
prop
yl-2
-hyd
roxy
prop
ylam
ine
Nitr
oso-
23-
dihy
drox
ypro
pyl-
2-ox
opro
pyla
min
eN
-Nitr
oso-
ethy
l-2-
oxop
ropy
lure
aN
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aN
itros
o-5-
met
hylo
xazo
lidon
eN
-Nit
roso
-N-m
ethy
lure
than
N-N
itros
o-1
3-ox
azol
idin
eN
-Nit
roso
-2-p
heny
leth
ylur
ea1
-Nit
roso
-34
5-t
rim
ethy
lpip
eraz
ine
Ure
than
ez V
inyl
chlo
ride
z
Mou
se63
Ace
tald
ehyd
em
ethy
lfor
myl
hydr
azon
eA
ciu
orfe
nA
F-2
z 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 2-
Am
ino-
4-( 5
-nitr
o-2-
fury
l)th
iazo
lez
tran
s-5-
Am
ino-
3[2-
( 5-n
itro-
2-fu
ryl)
viny
l] -1
24-
oxad
iazo
leA
reco
line
HC
lB
enza
ldeh
ydey
Ben
zofu
ranz
Ben
zotr
ichl
orid
eB
enzy
lace
tate
y B
enzy
lchl
orid
ey B
rom
oeth
anol
13
-But
adie
nez
But
ylat
edhy
drox
yani
sole
z 1
1-di
-N-B
utyl
hydr
azin
eC
affe
icac
idz
Cap
tafo
lz C
arba
zole
Cat
echo
lz 3-
Chl
oro-
2-m
ethy
lpro
pene
tec
hnic
algr
ade
( con
tain
ing
5di
met
hylv
inyl
chlo
ride
)z3
-(C
hlor
omet
hyl)
pyri
dine
HC
lz C
hlor
opre
nez
2-C
hlor
opro
pana
l1-
Chl
orop
rope
neC
ypro
tero
neac
etat
e1
1-D
ially
lhyd
razi
ne1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dic
hlor
vosz
Dig
lyci
dylr
esor
cino
leth
ert
echn
ical
grad
ez D
imet
hylv
inyl
chlo
ride
z D
init
roso
pipe
razi
neE
stra
diol
mus
tard
y E
thyl
acry
late
z Fo
rmic
acid
2-[ 4
-( 5
-nit
ro-2
-fur
yl) -
2-th
iazo
lyl] h
ydra
zide
z G
lyci
dolz
2-H
ydra
zino
-4-(
5-ni
tro-
2-fu
ryl)
thia
zole
z N
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
ICI
1628
46z
IQz
Isop
rene
Lov
asta
tin
MeI
Q1
-Met
hyl-
14-
dihy
dro-
7-[ 2
-(5-
nitr
ofur
yl) v
inyl
] -4-
oxo-
18-
naph
thyr
idin
e-3-
carb
oxyl
ate
pota
ssiu
m3
-(5-
Nitr
o-2-
fury
l)-
imid
azo(
12-
a) p
yrid
inez
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
N-[
4-( 5
-Nitr
o-2-
fury
l)-2
-thi
azol
yl] f
orm
amid
ez N
-Nit
roso
-N
-met
hylu
reaz
Nit
roso
dibu
tyla
min
ez N
-Nit
roso
hexa
met
hyle
neim
ine
N-N
itros
opip
erid
inez
b-P
ropi
olac
tone
z Se
sam
olz
Sty
rene
oxid
ez Te
lone
IIt
echn
ical
grad
ez N
-(T
rich
loro
met
hylth
io) p
htha
limid
e1
23-
Tri
chlo
ropr
opan
ez 2
22-
Tri
uo
ro-N
-[4-
( 5-n
itro
-2-f
uryl
) -2-
thia
zoly
l]ac
etam
idez
Tri
ur
alin
tec
hnic
algr
adey
Tri
s(2-
chlo
roet
hyl)
phos
phat
ez T
ris(
23-
dibr
omop
ropy
l)ph
osph
atez
Vin
ylac
etat
ez
Rat
85A
ceto
ne[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zone
1-A
ceto
xysa
frol
ey A
cryl
onitr
ile
1-A
llyl
-1-n
itro
sour
ea2
-Am
ino-
5-( 5
-nit
ro-2
-fur
yl) -
13
4-ox
adia
zole
2-
Am
ino-
5-( 5
-nitr
o-2-
fury
l)-1
34
-thi
adia
zole
2-A
min
o-4-
( 5-n
itro
-2-f
uryl
) thi
azol
ez 1-
Am
yl-1
-nit
roso
urea
Ari
stol
ochi
cac
id
sodi
umsa
lt( 7
7A
AI
21
AA
II)
Ben
zene
z B
enzo
( a) p
yren
ez 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bis
( 23
-dib
rom
opro
pyl)
phos
phat
em
agne
sium
salt
BL
-634
1H
Cl
N-n
-But
yl-N
-nitr
osou
rea
But
ylat
edhy
drox
yani
sole
z b
-But
yrol
acto
neC
affe
icac
idz
Cat
echo
lz 3-
Chl
oro-
2-m
ethy
lpro
pene
tec
hnic
algr
ade
( con
tain
ing
5di
met
hylv
inyl
chlo
ride
)z4
-Chl
oro-
o-ph
enyl
ened
iam
inez
Chl
oro
uoro
met
hane
3-
( Chl
orom
ethy
l)py
ridi
neH
Clz
Cip
rob
rate
z C
upfe
rron
z 1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
Dig
lyci
dylr
esor
cino
leth
ert
echn
ical
grad
ez 2
5-D
imet
hoxy
-4-a
min
osti
lben
ez D
imet
hylh
ydro
gen
phos
phit
ey 4
6-D
imet
hyl-
2-( 5
-nit
ro-2
-fu
ryl)
pyri
mid
ine
tran
s-2-
[(D
imet
hyla
min
o)m
ethy
limin
o]-5
-[2-
( 5-n
itro
-2-f
uryl
) vin
yl] -
13
4-ox
adia
zole
Dim
ethy
lvin
ylch
lori
dez
Epi
chlo
rohy
drin
y E
thyl
acry
late
z E
thyl
ene
oxid
ez 2-
Flu
oroe
thyl
-nitr
osou
rea
Gly
cido
lz N
-Hex
ylni
tros
oure
a1-
Hyd
roxy
anth
raqu
inon
e1-
( 2-H
ydro
xyet
hyl)
-1-
nitr
osou
reaz
1-( 3
-Hyd
roxy
prop
yl) -
1-ni
tros
oure
a1
-Hyd
roxy
safr
olez
ICI
1628
46z
Lox
tidin
eL
upit
idin
e3H
Cl
Mer
curi
cch
lori
dey
3-M
etho
xyca
tech
ol4
-Met
hoxy
phen
olN
-Met
hyl-
N-n
itro-
N-n
itros
ogua
nidi
nez
N-M
ethy
l-N
-nit
roso
benz
amid
e4-
Met
hylc
atec
hol
Met
hyln
itro
socy
anam
ide
3-( 5
-Nit
ro-2
-fur
yl) -
imid
azo(
12-
a) p
yrid
inez
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
4-( 5
-Nit
ro-2
-fur
yl) t
hiaz
ole
2-N
itro
uo
rene
8-N
itro
quin
olin
eN
itro
so-B
aygo
nN
-Nit
roso
-23
-dih
ydro
xypr
opyl
-2-h
ydro
xypr
opyl
amin
eN
itros
o-2
3-di
hydr
oxyp
ropy
l-2-
oxop
ropy
lam
ine
1-N
itro
so-3
5-d
imet
hyl-
4-be
nzoy
lpip
eraz
ine
N-N
itro
so-N
-met
hyl-
N-d
odec
ylam
ine
Nitr
oso-
N-m
ethy
l-N
-(2-
phen
yl) e
thyl
amin
eN
-Nit
roso
-N-m
ethy
ldec
ylam
ine
N-N
itro
so-N
-met
hylu
reaz
Nit
roso
-12
36
-tet
rahy
drop
yrid
ine
N-N
itro
sobe
nzth
iazu
ron
Nitr
osod
ibut
ylam
inez
N-N
itros
odie
thyl
amin
eN
-Nit
roso
ephe
drin
eN
itros
oeth
ylur
etha
nO
mep
razo
ley
Phen
acet
inz
Piv
alol
acto
ney
b-P
ropi
olac
tone
z N
-Pro
pyl-
N-n
itro
-N-n
itro
sogu
anid
ine
12-
Pro
pyle
neox
idez
Ses
amol
z St
yren
eox
idez
Sulf
alla
tez
Telo
neII
tec
hnic
algr
adez
12
3-T
rich
loro
prop
anez
24
6-T
rim
ethy
lani
line
HC
lz
646
Subc
utan
eous
Mou
se4
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 1
2-D
ibro
moe
than
ez N
2-c
-Glu
tam
yl-p
-hyd
razi
nobe
nzoi
cac
idG
lyci
dolz
tissu
eR
at13
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 2
4-D
iam
inot
olue
ne2
HC
lz 1
2-D
ichl
oroe
than
ez D
imet
hoxa
ne1
4-D
ioxa
nez
MeA
-a-C
acet
atez
44
-Met
hyle
ne-b
is( 2
-met
hyla
nili
ne)
o-N
itro
soto
luen
ep-
Ros
anili
neH
Clz
Tolu
ene
diis
ocya
nate
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
o-T
olui
dine
HC
lz 2
45-
Tri
met
hyla
nilin
eH
Clz
25-
Xyl
idin
eH
Clz
Test
isM
ouse
4D
ieth
ylst
ilbe
stro
lz Fi
nast
erid
eR
eser
pine
z Ta
mox
ifen
citr
atez
Rat
185-
Aza
cytid
inez
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 1
3-B
utad
iene
z N
-But
yl-N
-(4-
hydr
oxyb
utyl
) nitr
osam
ine
Cad
miu
mch
lori
de
2-C
hlor
o-1
11-
tri
uoro
etha
ne1
1-D
ichl
oro-
1-u
oroe
than
eH
ydro
chlo
rou
oroc
arbo
n12
3M
ethy
lter
t-bu
tyle
ther
z M
ethy
lclo
fena
pate
z M
etro
nida
zole
z N
-Nit
roso
dim
ethy
lam
inez
Oxo
linic
acid
y SD
Z20
0-11
01
11
2-Te
tra
uoro
etha
ney
Tri
chlo
roet
hyle
nez
Tri
nitr
ogly
ceri
nV
inyl
chlo
ride
z
Thy
roid
glan
dH
amst
er4
Hex
achl
orob
enze
nez
Hyd
razi
nez
Met
hylt
hiou
raci
lU
reth
anez
Mou
se18
3-A
min
o-4-
etho
xyac
etan
ilide
y H
Cbl
ueno
1z
tert
-But
ylal
coho
lz C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
24
-Dia
min
oani
sole
sulf
atez
Die
thyl
stil
best
rolz
Dox
ylam
ine
succ
inat
ez E
thio
nam
idey
Eth
ylen
eth
iour
eaz
44
-Met
hyle
nedi
anil
ine
2HC
lz 1
5-N
apht
hale
nedi
amin
ez N
itrob
enze
nez
Oxa
zepa
my
44
-Oxy
dian
iline
z C
Ip
igm
entr
ed3z
Sulf
amet
hazi
ne2
37
8-T
etra
chlo
rodi
benz
o-p-
diox
inz
44
-Thi
odia
nilin
ez
Rat
33A
cryl
amid
e3-
Am
inot
riaz
olez
o-A
nisi
dine
HC
lz B
emit
radi
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bro
mat
epo
tass
ium
z C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
Chl
orop
rene
z 2
4-D
iam
inoa
niso
lesu
lfat
ez N
N-D
ieth
ylth
iour
eay
1-E
thyl
-1-n
itro
sour
ea
Eth
ylen
eth
iour
eaz
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Flu
vast
atin
Gly
cido
lz Io
dina
ted
glyc
erol
z Is
obut
eney
Mal
onal
dehy
des
odiu
msa
ltz
Met
him
azol
e4
4-M
ethy
lene
bis(
NN
-dim
ethy
l)be
nzen
amin
ez 4
4-M
ethy
lene
dian
iline
2H
Clz
Mir
exp
hoto
-N
itro
benz
enez
N-N
itro
sobi
s(2-
oxop
ropy
l)am
ine
44
-Oxy
dian
iline
z Pr
opyl
thio
urac
ilz p-
Ros
anil
ine
HC
lz 2
37
8-Te
trac
hlor
odib
enzo
-p-d
ioxi
nz 4
4-T
hiod
iani
linez
Thi
oura
cilz
Tri
met
hylt
hiou
reay
Vin
ylac
etat
ez Z
inc
dim
ethy
ldith
ioca
rbam
atez
Uri
nary
blad
der
Dog
23
3-D
ichl
orob
enzi
dine
44
-Met
hyle
ne-b
is( 2
-chl
oroa
nilin
e)H
amst
er3
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-t
hiaz
olyl
] hyd
razi
dez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
acet
amid
eN
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] for
mam
idez
Mou
se12
2-A
cety
lam
ino
uore
nez
4-A
min
odip
heny
l2-
Am
inod
iphe
nyle
neox
ide
o-A
nisi
dine
HC
lz 4-
Chl
oro-
4-a
min
odip
heny
leth
erz
p-C
resi
dine
z 4-
Eth
ylsu
lpho
nyln
apht
hale
ne-1
-sul
fona
mid
eN
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez P
hena
cetin
z Te
lone
IIt
echn
ical
grad
ez U
raci
lz
Mon
key
12-
Nap
hthy
lam
inez
Rat
49A
ceta
min
ophe
nz A
llyli
soth
iocy
anat
ey 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 2-
Am
ino-
4-( 5
-nitr
o-2-
fury
l)th
iazo
lez
4-A
min
o-2-
nitr
ophe
noly
11-A
min
ound
ecan
oic
acid
y o-
Ani
sidi
neH
Clz
Ari
stol
ochi
cac
ids
odiu
msa
lt( 7
7A
AI
21
AA
II)
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez C
Id
ispe
rse
blue
1y N
-But
yl-N
-(4-
hydr
oxyb
utyl
) nitr
osam
ine
4-C
hlor
o-o-
phen
ylen
edia
min
ez m
-Cre
sidi
ney
p-C
resi
dine
z C
yclo
phos
pham
idez
Die
thyl
ene
glyc
olD
imet
hyla
rsin
icac
idy
Fose
tylA
lIQ
HC
lM
eA-a
-Cac
etat
ez M
elam
iney
2-M
etho
xy-3
-am
inod
iben
zofu
ran
2-N
apht
hyla
min
ez N
itril
otri
acet
icac
idz
Nitr
ilot
riac
etic
acid
tri
sodi
umsa
ltm
onoh
ydra
tey
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez o-
Nitr
oani
sole
z N
-Nitr
oso-
N-m
ethy
l-N
-dod
ecyl
amin
eN
-Nitr
oso-
N-m
ethy
l-N
-tet
rade
cyla
min
eN
-Nit
roso
-N-m
ethy
ldec
ylam
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
Nitr
osod
ibut
ylam
inez
N-N
itro
sodi
phen
ylam
iney
o-N
itros
otol
uene
N-O
xydi
ethy
lene
thio
carb
amyl
-N-o
xydi
ethy
lene
sulf
enam
ide
Phe
nace
tinz
Phen
azon
eo-
Phen
ylph
enat
eso
dium
y o-
Phen
ylph
enol
y P
otas
sium
bica
rbon
ate
Purp
urin
Que
rcet
iny
p-Q
uino
nedi
oxim
ey Sa
ccha
rin
sodi
umy
Sali
cyla
zosu
lfap
yrid
inez
o-To
luen
esul
fona
mid
eo-
Tolu
idin
eH
Clz
Trp
-P-2
acet
atez
Ura
cilz
Ute
rus
Ham
ster
1N
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aM
ouse
12B
rom
oeth
anez
Chl
oroe
than
ey D
acar
bazi
nez
12-
Dic
hlor
oeth
anez
Die
thyl
stil
best
rolz
Eth
ylen
eox
idez
Gly
cido
lz ( N
-6) -
( Met
hyln
itros
o)ad
enos
ine
Proc
arba
zine
HC
lz 1
23-
Tri
chlo
ropr
opan
ez T
rim
ethy
lpho
spha
tey
Vin
ylac
etat
ez
Rat
26A
cryl
amid
e1-
Ally
l-1-
nitr
osou
rea
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
1-A
myl
-1-n
itros
oure
aA
traz
iney
CI
dir
ectb
lue
15B
rom
ocri
ptin
em
esyl
atey
N-n
-But
yl-N
-nit
roso
urea
Cal
cium
valp
roat
eC
apta
nz 2-
Chl
oro-
11
1-tr
iuo
roet
hane
Dac
arba
zine
z D
amin
ozid
ez 3
3-D
imet
hoxy
benz
idin
e-4
4-d
iisoc
yana
tey
33
-Dim
etho
xybe
nzid
ine
2HC
lD
imet
hyla
min
oeth
ylni
tros
oeth
ylur
ean
itri
tesa
lt1-
Eth
ylni
tros
o-3-
( 2-h
ydro
xyet
hyl)
-ure
a1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
N-H
exyl
nitr
osou
rea
ICR
F-1
59z
Isop
hosp
ham
idez
15-
Nap
htha
lene
diam
inez
Nit
robe
nzen
ez N
orle
stri
nz 4
4-T
hiod
iani
linez
Vin
ylac
etat
ez
Vag
ina
Mou
se1
AZ
Tz
Rat
2A
ZT
z N
-n-B
utyl
-N-n
itro
sour
ea( C
ontin
ued
onne
xtpa
ge)
647
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Vas
cula
rsy
stem
Ham
ster
91
2-D
imet
hylh
ydra
zine
2H
Cl
Gly
cido
lz H
exac
hlor
oben
zene
z N
-Nit
roso
-eth
yl-2
-oxo
prop
ylur
eaN
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aN
-Nitr
oso-
oxop
ropy
lchl
oroe
thyl
urea
N-N
itro
so-o
xopr
opyl
urea
N-N
itros
o-2-
phen
ylet
hylu
rea
Vin
ylch
lori
dez
Mou
se59
A-a
-CN
-Ace
tyl-
4-( h
ydro
xym
ethy
l)ph
enyl
hydr
azin
e1-
Ace
tyl-
2-ph
enyl
hydr
azin
eA
llyl
hydr
azin
eH
Cl
Are
colin
eH
Cl
Aza
thio
prin
eB
enzi
dine
2H
Cl
2-B
iphe
nyla
min
eH
Cly
13-
But
adie
nez
Cap
tafo
lz C
arba
myl
hydr
azin
eH
Cl
4-C
hlor
o-4
-am
inod
iphe
nyle
ther
z 1-
Chl
oro-
4-ni
trob
enze
ney
5-C
hlor
o-o-
tolu
idin
ey 4-
Chl
oro-
o-to
luid
ine
HC
ly p-
Chl
oroa
nilin
eH
Clz
Chl
orop
rene
z C
upfe
rron
z D
acar
bazi
nez
Dam
inoz
idez
24-
Dia
min
otol
uene
2H
Clz
12-
Dib
rom
oeth
anez
Dif
talo
ne7
12-
Dim
ethy
lben
z(a)
anth
race
ne1
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
N-E
thyl
-N-f
orm
ylhy
draz
ine
Eth
ylhy
draz
ine
HC
lG
lu-P
-1z
Glu
-P-2
z p-
Hyd
razi
nobe
nzoi
cac
idH
Cl
1-H
ydro
xysa
frol
ez Is
opre
neM
eA-a
-Cac
etat
ez N
-Met
hyl-
N-f
orm
ylhy
draz
ine
2-M
ethy
l-1-
nitr
oant
hraq
uino
nez
Mic
hler
rsquoske
tone
z 5-
Nitr
o-o-
tolu
idin
ey N
itro
fenz
N-N
itros
o-N
-met
hylu
reaz
Pent
achl
oroa
niso
lez
23
45
6-Pe
ntac
hlor
ophe
nol(
Dow
icid
eE
C-7
)y2
34
56
-Pen
tach
loro
phen
olt
echn
ical
grad
ez n-
Pen
tylh
ydra
zine
HC
lPh
enyl
ethy
lhyd
razi
nesu
lfat
ePh
enyl
hydr
azin
eH
Cl
Ster
igm
atoc
ysti
nz Te
tra
uoro
ethy
lene
z To
luen
edi
isoc
yana
tec
omm
erci
algr
ade
( 24
( 80
) -an
d2
6( 2
0) -
)zo
-Tol
uidi
neH
Clz
24
6-T
rich
loro
anil
iney
24
5-T
rim
ethy
lani
line
HC
lz 2
46-
Tri
met
hyla
nili
neH
Clz
Ure
than
ez V
inyl
carb
amat
eV
inyl
chlo
ride
z V
inyl
uor
idez
Vin
ylid
ene
chlo
ride
y 2
5-X
ylid
ine
HC
lz
Mon
key
2A
ato
xin
B1y
Ure
than
ez
Rat
32A
nilin
eH
Cly
Azo
benz
eney
Ben
zene
z C
livor
ine
Cup
ferr
onz
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
Z-E
thyl
-ON
N-a
zoxy
etha
neZ
-Eth
yl-O
NN
-azo
xym
etha
neI
QH
Cl
Las
ioca
rpin
e4
4-M
ethy
lene
-bis
( 2-c
hlor
oani
line)
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
N-N
itros
o-( 2
-hyd
roxy
prop
yl) -
( 2-h
ydro
xyet
hyl)
amin
eN
itro
so-1
23
6-t
etra
hydr
opyr
idin
eN
-Nitr
osob
is( 2
-oxo
prop
yl) a
min
eN
-Nit
roso
diet
hano
lam
ine
N-N
itro
sodi
ethy
lam
ine
N-N
itros
odim
ethy
lam
inez
N-N
itros
omet
hyl-
( 2-t
osyl
oxye
thyl
) am
ine
N-N
itros
omor
phol
ine
N-N
itro
sopy
rrol
idin
ez Pe
tasi
teni
neS
teri
gmat
ocys
tinz
Sym
phyt
ine
Tetr
auo
roet
hyle
nez
o-To
luid
ine
HC
lz T
rp-P
-2ac
etat
ez V
inyl
brom
ide
Vin
ylch
lori
dez
Vin
yl
uori
dez
aT
here
was
nore
port
edta
rget
site
in1
spec
ies
( rat
sor
mic
e)fo
r5
chem
ical
sw
ithsu
pers
crip
tsb
utth
ech
emic
alw
asev
alua
ted
byth
epu
blis
hed
auth
oras
aca
rcin
ogen
ald
rinz
diel
drin
z N
-nit
roso
pyrr
olid
inez
23
45
6-pe
ntac
hlor
ophe
nol
( Dow
icid
eE
C-7
)ya
ndur
etha
nez
bN
asal
cavi
tyin
clud
estis
sues
ofth
eno
sen
asal
turb
inat
esp
aran
asal
sinu
ses
and
trac
hea
c Ora
lcav
ityin
clud
estis
sues
ofth
em
outh
oro
phar
ynx
phar
ynx
and
lary
nx
Ach
emic
alis
liste
dun
der
each
orga
nev
alua
ted
aspo
sitiv
ein
anex
peri
men
tin
that
spec
ies
byat
leas
t1au
thor
The
refo
rea
chem
ical
may
beli
sted
unde
rse
vera
ltar
geto
rgan
san
dev
ery
chem
ical
liste
din
the
tabl
eis
posi
tive
inat
leas
t1sp
ecie
sIn
orde
rto
com
pare
resu
ltsin
rats
and
mic
esy
mbo
lsfo
llow
chem
ical
ste
sted
inbo
thsp
ecie
sa
zin
dica
tes
that
the
chem
ical
ispo
sitiv
eat
som
esi
tein
both
spec
ies
and
ay
indi
cate
sth
atit
was
test
edin
both
butp
ositi
vein
only
1a
Nth
enu
mbe
rof
chem
ical
sw
ithat
leas
t1po
sitiv
ete
stat
that
site
inth
atsp
ecie
sB
ecau
sem
any
chem
ical
sin
duce
tum
ors
atm
ore
than
1si
tein
agi
ven
spec
ies
man
ych
emic
als
appe
arm
ore
than
once
inth
eta
ble
648
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649
species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters
RESULTS IN RATS AND MICE
For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens
TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database
Chemicals evaluated as carcinogenic in
Rats Mice
All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)
Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2
a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not
b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats
All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical
to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included
The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site
Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common
650 GOLD ET AL TOXICOLOGIC PATHOLOGY
TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)
Target site Agent mixture or industrial process
Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e
Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke
Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products
Brain Vinyl chloride a
Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e
Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena
Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system
Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as
a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell
lymphotropic virus type I (HTLV-I) Vinyl chloridea
Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production
Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)
Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea
Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea
Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)
Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea
Mesenchymal tumors Azathioprinea
Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust
Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust
Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid
(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke
Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production
8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots
Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e
Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays
IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD
IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no
tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance
is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651
sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites
Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to
be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)
Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)
Target Organs of Human CarcinogensTo complement the compendium of target organs in car-
cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke
In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)
Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens
Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from
bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)
ACKNOWLEDGMENTS
We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention
REFERENCES
1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56
2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600
3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998
4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685
5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404
6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605
7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246
8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100
9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash
23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC
11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the
652 GOLD ET AL TOXICOLOGIC PATHOLOGY
US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240
12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute
13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program
14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX
15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11
16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash
34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c
Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Mon
key
1P
roca
rbaz
ine
HC
lz
Rat
56A
llyl
isov
aler
atez
1-A
myl
-1-n
itros
oure
aA
traz
iney
Ben
zidi
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
CI
dir
ectb
lue
15
N-n
-But
yl-N
-nitr
osou
rea
Cad
miu
mch
lori
deC
hlor
ambu
cilz
Cyc
loph
osph
amid
ez D
acar
bazi
nez
13-
Dib
utyl
-1-n
itro
sour
eaD
ichl
oroa
cety
lene
z 3
3-D
ichl
orob
enzi
dine
Dic
hlor
vosz
Dim
etho
xane
33
-Dim
etho
xybe
nzid
ine-
44
-dii
socy
anat
ey 3
3-D
imet
hoxy
benz
idin
e2H
Cl
Dim
ethy
lmor
phol
inop
hosp
hora
mid
atey
2-( 2
2-D
imet
hylh
ydra
zino
) -4-
( 5-n
itro-
2-fu
ryl)
thia
zole
Eth
ylen
eox
idez
Form
alde
hyde
z Fo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z F
uran
z G
lyci
dolz
FD
ampC
gree
nno
1y
FDamp
Cgr
een
no2
y H
emat
oxyl
in2
-Hyd
razi
no-4
-(p-
amin
ophe
nyl)
thia
zole
z H
ydro
quin
onez
1-( 2
-Hyd
roxy
ethy
l)-1
-nit
roso
urea
z Io
dina
ted
glyc
erol
z L
asio
carp
ine
2-M
erca
ptob
enzo
thia
zole
y M
etep
aM
ethy
lter
t-bu
tyle
ther
z M
irex
z l-
5-M
orph
olin
omet
hyl-
3-[(
5-ni
trof
urfu
ryli
dene
) am
ino]
-2-o
xazo
lidi
none
H
Cl
Nit
rite
sod
ium
y N
-[5-
( 5-N
itro-
2-fu
ryl)
-13
4-t
hiad
iazo
l-2-
yl] a
ceta
mid
ez o-
Nit
roan
isol
ez 1-
[(5-
Nitr
ofur
fury
liden
e)am
ino]
-2-i
mid
azol
idin
one
1-N
itro
pyre
neN
itros
o-N
-met
hyl-
N-(
2-ph
enyl
) eth
ylam
ine
N-N
itros
odie
than
olam
ine
PhIP
HC
lz P
roca
rbaz
ine
HC
lz P
ropa
nesu
ltone
N-P
ropy
l-N
-nit
roso
urea
FD
ampC
red
no2
FD
ampC
red
no4
y Te
trac
hlor
oeth
ylen
ez Te
tra
uoro
ethy
lene
z T
hio-
tepa
z 2
46-
Tri
chlo
roph
enol
z T
rp-P
-2ac
etat
ez
Kid
ney
Ham
ster
1B
rom
ate
pota
ssiu
mz
Mou
se26
o-B
enzy
l-p-
chlo
roph
enol
y 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bro
mat
epo
tass
ium
z B
rom
odic
hlor
omet
hane
z 1
3-B
utad
iene
z 1
2-di
-n-B
utyl
hydr
azin
e2H
Cl
Caf
feic
acid
z C
hlor
ofor
mz
Chl
orop
rene
z D
amin
ozid
ez 2
4-D
iam
inop
heno
l2H
Cly
Dic
hlor
oace
tyle
nez
24-
Din
itrot
olue
ne( c
onta
inin
g1
0-1
52
6-di
nitr
otol
uene
)zH
ydro
quin
onez
N-H
ydro
xy-2
-ace
tyla
min
ouo
rene
z 3-
Hyd
roxy
-p-b
utyr
ophe
neti
dide
L
ead
acet
ate
basi
cz M
ercu
rym
ethy
lchl
orid
eN
itril
otri
acet
icac
idz
Och
rato
xin
Az
Phe
nace
tinz
CI
pig
men
tred
3z St
rept
ozot
ocin
z T
ris(
2-ch
loro
ethy
l)ph
osph
atez
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez V
inyl
iden
ech
lori
dey
Mon
key
1C
ycas
inan
dm
ethy
lazo
xym
etha
nola
ceta
teR
at86
A
atox
inB
1y 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 1-
Am
ino-
2-m
ethy
lant
hraq
uino
nez
2-A
min
o-5-
( 5-n
itro-
2-fu
ryl)
-13
4-o
xadi
azol
e2-
Am
ino-
5-( 5
-nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
e2-
Am
ino-
4-ni
trop
heno
ly 2-
Am
ino-
5-ni
trot
hiaz
oley
o-A
nisi
dine
HC
lz A
rist
oloc
hic
acid
so
dium
salt
( 77
AA
I21
A
AII
) A
zoxy
met
hane
Bar
bita
lso
dium
Ben
zofu
ranz
Bro
mat
epo
tass
ium
z B
rom
odic
hlor
omet
hane
z te
rt-B
utyl
alco
holz
Caf
feic
acid
z C
apta
folz
Cap
tanz
Chl
orin
ated
para
fns
( C12
60
chlo
rine
)zC
hlor
ofor
mz
3-( p
-Chl
orop
heny
l)-1
1-d
imet
hylu
reay
Chl
orop
rene
z C
hlor
otha
loni
ly C
inna
myl
anth
rani
late
z C
itrin
inC
oum
arin
z D
ichl
oroa
cety
lene
z 1
4-D
ichl
orob
enze
nez
Die
thyl
acet
amid
e3
4-D
ihyd
roco
umar
inz
Dim
etho
xane
Dim
ethy
lmet
hylp
hosp
hona
tey
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
N-4
-(4
-Flu
orob
iphe
nyl)
acet
amid
eFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z G
lyci
neH
exac
hlor
obut
adie
ne
Hex
achl
oroe
than
ez H
exam
ethy
lmel
amin
e2-
Hyd
razi
no-4
-(5-
nitr
o-2-
fury
l)th
iazo
lez
Hyd
roqu
inon
ez 1-
( 2-H
ydro
xyet
hyl)
-1-n
itro
sour
eaz
Isop
horo
ney
Lea
dac
etat
ey L
ead
acet
ate
basi
cz d-
Lim
onen
ey 2-
Met
hoxy
-3-a
min
odib
enzo
fura
n8-
Met
hoxy
psor
alen
Z-M
ethy
l-O
NN
-azo
xyet
hane
Met
hylt
ert-
buty
leth
erz
N-(
N-M
ethy
l-N
-nit
roso
carb
amoy
l)-l
-orn
ithi
nea
-Met
hylb
enzy
lalc
ohol
y M
irex
z l-
5-M
orph
olin
omet
hyl-
3-[(
5-ni
trof
urfu
rylid
ene)
amin
o]-2
-oxa
zolid
inon
eH
Cl
Nit
rilo
tria
ceti
cac
idz
Nit
rilo
tria
cetic
acid
tri
sodi
umsa
ltm
onoh
ydra
tey
3-( 5
-Nitr
o-2-
fury
l)-i
mid
azo(
12-
a) p
yrid
inez
N-[
3-( 5
-Nitr
o-2-
fury
l)-1
24
-oxa
diaz
ole-
5-yl
] -m
ethy
l]ac
etam
ide
N-[
5-( 5
-Nitr
o-2-
fury
l)-1
34
-thi
adia
zol-
2-yl
] ace
tam
idez
o-N
itro
anis
olez
Nitr
oben
zene
z 2-
Nit
ro
uore
ne
1-[(
5-N
itrof
urfu
rylid
ene)
amin
o]hy
dant
oinz
1-N
itro
so-1
-hyd
roxy
ethy
l-3-
chlo
roet
hylu
rea
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
diet
hyla
min
eN
-Nitr
osod
imet
hyla
min
ez N
-Nit
roso
pyrr
olid
inez
Och
rato
xin
Az
CI
aci
dor
ange
3y N
-Oxy
diet
hyle
neth
ioca
rbam
yl-N
-oxy
diet
hyle
nesu
lfen
amid
eP
hena
cetin
z Ph
enaz
one
Phen
olph
thal
einz
Phen
ylbu
tazo
nez
o-Ph
enyl
phen
ate
sodi
umy
Que
rcet
iny
Salic
ylaz
osul
fapy
ridi
nez
Str
epto
zoto
cinz
Tetr
achl
oroe
thyl
enez
Tetr
auo
roet
hyle
nez
Tetr
ahyd
rofu
ranz
12
3-T
rich
loro
prop
anez
Tri
s(2-
chlo
roet
hyl)
phos
phat
ez T
ris(
23-
dibr
omop
ropy
l)ph
osph
atez
Vin
ylch
lori
dez
Lar
gein
test
ine
Ham
ster
51
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
Hyd
razi
nez
Met
hylh
ydra
zine
Ure
than
ezM
ouse
1C
apsa
icin
Rat
32A
at
oxin
B1y
1-A
llyl
-1-n
itros
oure
a1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z A
myl
opec
tin
sulf
ate
Azo
xym
etha
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
te
chni
calg
rade
z C
Id
irec
tblu
e15
Bro
mod
ichl
orom
etha
nez
N-N
-But
yl-n
-nitr
osou
rea
Car
rage
enan
aci
d-de
grad
edC
hrys
azin
z D
extr
ansu
lfat
eso
dium
( DS-
M-1
) 3
3-D
imet
hoxy
benz
idin
e2H
Cl
33
-Dim
ethy
lben
zidi
ne2
HC
lz Z
-Eth
yl-O
NN
-azo
xym
etha
ne1
-Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-t
hiaz
olyl
] hyd
razi
dez
Glu
-P-1
z G
lu-P
-2z
Gly
cido
lz N
-Hex
ylni
tros
oure
a1-
Hyd
roxy
anth
raqu
inon
e1-
( 2-H
ydro
xyet
hyl)
-1-n
itro
sour
eaz
IQz
o-N
itro
anis
olez
N-N
itro
sobi
s(2-
oxop
ropy
l)am
ine
Phe
nazo
pyri
dine
HC
lz P
hIP
HC
lz C
Ia
cid
red
114
44
-Thi
odia
nilin
ez T
ribr
omom
etha
ney
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez
Liv
erD
og2
33
-Dic
hlor
oben
zidi
ne4
4-M
ethy
lene
-bis
( 2-c
hlor
oani
line
)H
amst
er16
2-A
cety
lam
ino
uore
nez
pp
-DD
Ey
12-
Dim
ethy
lhyd
razi
ne2
HC
lH
exac
hlor
oben
zene
z H
ydra
zine
sulf
atez
N-H
ydro
xy-2
-ace
tyla
min
ouo
rene
z N
-Met
hyl-
N-f
orm
ylhy
draz
ine
Met
hylh
ydra
zine
Met
hyln
itros
amin
o-N
N-d
imet
hyle
thyl
amin
eN
-Nitr
oso-
13-
oxaz
olid
ine
Nit
roso
-2-o
xopr
opyl
etha
nola
min
eN
-Nitr
osoa
llyl-
2-ox
opro
pyla
min
eN
-Nit
roso
azet
idin
eN
-Nit
roso
mor
phol
ine
N-N
itros
opip
erid
inez
N-N
itros
opyr
rolid
inez
Mou
se23
1A
-a-C
Ace
tam
inop
henz
2-A
cety
lam
ino
uore
nez
Aci
uor
fen
Ald
rinz
1-A
min
o-2
4-di
brom
oant
hraq
uino
nez
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
1-A
min
o-2-
met
hyla
nthr
aqui
none
z 2-
Am
inoa
nthr
aqui
none
z 4-
Am
inod
iphe
nyl
2-A
min
odip
heny
lene
oxid
e3-
Am
inot
riaz
olez
Ara
mite
z A
rocl
or12
54y
Aur
amin
e-O
z B
enzi
dine
2H
Cl
Ben
zofu
ranz
Ben
zyla
ceta
tey
3-B
enzy
lsyd
none
-4-a
ceta
mid
ez B
is( 2
-chl
oro-
1-m
ethy
leth
yl) e
ther
tec
hnic
algr
adey
Bis
-2-c
hlor
oeth
ylet
her
Bis
-2-h
ydro
xyet
hyld
ithio
carb
amic
acid
pot
assi
umC
Id
irec
tbla
ck38
CI
dir
ectb
lue
218z
HC
blue
no1
z H
Cbl
ueno
1( p
uri
ed)
Bro
mod
ichl
orom
etha
nez
13-
But
adie
nez
But
ylat
edhy
drox
ytol
uene
y 1
1-di
-n-B
utyl
hydr
azin
eC
apta
folz
Car
bazo
le
Car
bon
tetr
achl
orid
ez C
hlor
alhy
drat
eC
hlor
ambe
ny C
hlor
dane
tec
hnic
algr
adey
Chl
oren
dic
acid
z C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
1-
Chl
oro-
2-ni
trob
enze
ney
1-C
hlor
o-4-
nitr
oben
zene
y 4-
Chl
oro-
m-p
heny
lene
diam
inez
4-C
hlor
o-o-
phen
ylen
edia
min
ez 5-
Chl
oro-
o-to
luid
iney
642
[ 4-C
hlor
o-6-
( 23
-xyl
idin
o)-2
-pyr
imid
inyl
thio
] ace
ticac
idz
4-C
hlor
o-6-
( 23
-xyl
idin
o)-2
-pyr
imid
inyl
thio
( N-b
-hyd
roxy
ethy
l)ac
etam
idez
Chl
oroa
ceta
ldeh
yde
p-C
hlor
oani
line
HC
lz C
hlor
oben
zila
tey
Chl
orod
ibro
mom
etha
ney
Chl
orof
orm
z C
hlor
opre
nez
Chr
ysaz
inz
CI-
924
Cin
nam
ylan
thra
nila
tez
Cip
ro
brat
ez C
lobu
zari
ty C
ompo
und
LY17
1883
Cou
mar
inz
p-C
resi
dine
z C
upfe
rron
z C
ycla
mat
eso
dium
y C
yclo
chlo
roti
neC
ypro
tero
neac
etat
ep
p-D
DD
y p
p-D
DE
y D
DT
z D
ialla
te2
4-D
iam
inot
olue
nez
24-
Dia
min
otol
uene
2H
Clz
35-
Dic
hlor
o-( N
-11
-dim
ethy
l-2-
prop
ynyl
) ben
zam
ide
26-
Dic
hlor
o-p-
phen
ylen
edia
min
ey D
ichl
oroa
cetic
acid
z 1
4-D
ichl
orob
enze
nez
12-
Dic
hlor
opro
pane
y D
icof
oly
Die
ldri
nz D
ifta
lone
34
-Dih
ydro
coum
arin
z D
ihyd
rosa
frol
ez 2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 1
1-D
imet
hylh
ydra
zine
y 1
4-D
ioxa
nez
55-
Dip
heny
lhyd
anto
iny
Dip
yron
ey D
oxyl
amin
esu
ccin
atez
Est
rago
led
l-E
thio
nine
z o-
Eth
oxyb
enza
mid
eN
-Eth
yl-N
-for
myl
hydr
azin
eE
thyl
ene
imin
eE
thyl
ene
thio
urea
z 2-
Eth
ylhe
xano
ly di
( 2-E
thyl
hexy
l)ad
ipat
ey di
( 2-E
thyl
hexy
l)ph
thal
atez
4-F
luor
o-4-
amin
odip
heny
lF
uran
z Fu
rfur
alz
Gen
tian
viol
etG
lu-P
-1z
Glu
-P-2
z G
lyci
dolz
Gri
seof
ulvi
nH
CD
Dm
ixtu
rez
Hep
tach
lory
Hex
achl
orob
enze
nez
a-1
23
45
6-H
exac
hlor
ocyc
lohe
xane
z b
-12
34
56
-Hex
achl
oroc
yclo
hexa
nec
-12
34
56
-Hex
achl
oroc
yclo
hexa
ney
Hex
achl
oroc
yclo
hexa
ne
tech
nica
lgra
deH
exac
hlor
oeth
anez
Hex
anal
met
hylf
orm
ylhy
draz
one
Hyd
razi
nesu
lfat
ez H
ydra
zobe
nzen
ez H
ydro
quin
onez
N-H
ydro
xy-2
-ac
etyl
amin
ouo
rene
z 1
-Hyd
roxy
estr
agol
e2-
Hyd
roxy
ethy
lhyd
razi
ne1
-Hyd
roxy
safr
olez
IQz
Ison
iazi
dz Is
opre
neK
epon
ez L
eupe
ptin
Lov
asta
tinL
uteo
skyr
inM
alon
alde
hyde
sod
ium
saltz
MeA
-a-C
acet
atez
MeI
QM
eIQ
xz M
ethi
dath
ion
3-M
etho
xy-4
-am
inoa
zobe
nzen
eM
ethy
lter
t-bu
tyle
ther
z M
ethy
lclo
fena
pate
z N
-Met
hyl-
N-f
orm
ylhy
draz
ine
3-M
ethy
lbut
anal
met
hylf
orm
ylhy
draz
one
44
-Met
hyle
ne-b
is( 2
-chl
oroa
nili
ne)
2HC
ly M
ethy
lene
chlo
ride
z 4
4-M
ethy
lene
bis(
NN
-dim
ethy
l)be
nzen
amin
ez 4
4-M
ethy
lene
dian
iline
2H
Clz
Met
hylh
ydra
zine
N-M
ethy
lola
cryl
amid
ey M
ethy
lphe
nida
teH
Cly
Mic
hler
rsquoske
tone
z M
irex
z 1
5-N
apht
hale
nedi
amin
ez 2-
Nap
hthy
lam
inez
Nit
hiaz
idez
3-N
itro-
p-ac
etop
hene
tidey
5-N
itro-
o-an
isid
inez
2-N
itro
-p-p
heny
lene
diam
iney
5-N
itro
-o-t
olui
dine
y 5-
Nitr
oace
naph
then
ez o-
Nitr
oani
sole
z N
itrob
enze
nez
6-N
itrob
enzi
mid
azol
ey N
itro
fenz
Nit
rom
etha
nez
Nitr
osod
ibut
ylam
inez
N-N
itros
odim
ethy
lam
inez
p-N
itros
odip
heny
lam
inez
N-N
itro
sohe
xam
ethy
lene
imin
eN
-Nit
roso
pipe
ridi
nez
Non
abro
mob
iphe
nyl
Och
rato
xin
Az
Oxa
zepa
my
44
-Oxy
dian
iline
z Pe
ntac
hlor
oeth
aney
Pent
achl
oron
itrob
enze
ney
23
45
6-Pe
ntac
hlor
ophe
nol(
Dow
icid
eE
C-7
)y 2
34
56-
Pen
tach
loro
phen
olt
echn
ical
grad
ez P
enta
nalm
ethy
lfor
myl
hydr
azon
eP
hena
zopy
ridi
neH
Clz
Phe
noba
rbit
aly
Phen
obar
bita
lso
dium
z Ph
enyl
buta
zone
z o-
Phen
ylen
edia
min
e2H
Clz
Pipe
rony
l-bu
toxi
dez
Pipe
rony
lsul
foxi
dey
Poly
brom
inat
edbi
phen
ylm
ixtu
rez
Prob
enec
idy
N-N
-Pro
pyl-
N-f
orm
ylhy
draz
ine
Damp
Cre
dno
5z
Rif
ampi
ciny
Rip
azep
amy
p-R
osan
iline
HC
lz S
afro
lez
Sali
cyla
zosu
lfap
yrid
inez
Sel
eniu
mdi
ethy
ldith
ioca
rbam
ate
Sel
eniu
msu
lde
z S
trob
ane
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
11
12-
Tetr
achl
oroe
than
ey 1
12
2-Te
trac
hlor
oeth
aney
Tetr
achl
oroe
thyl
enez
Tetr
achl
orvi
npho
sy Te
tra
uoro
-m-p
heny
lene
diam
ine
2HC
ly Te
tra
uoro
ethy
lene
z Te
trah
ydro
fura
nz T
hioa
ceta
mid
ez 4
4-T
hiod
iani
linez
Thi
oura
cilz
Tolu
ene
diis
ocya
nate
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
m-T
olui
dine
HC
ly o-
Tolu
idin
eH
Clz
p-To
luid
ine
HC
ly To
xaph
eney
T-2
toxi
nT
riam
tere
ney
Tri
chlo
roac
etic
acid
y 2
46-
Tri
chlo
roan
iline
y 1
12-
Tri
chlo
roet
hane
y T
rich
loro
ethy
lene
z T
rich
loro
ethy
lene
( wit
hout
epic
hlor
ohyd
rin)
y 2
46-
Tri
chlo
roph
enol
z 1
23-
Tri
chlo
ropr
opan
ez T
ri
ural
int
echn
ical
grad
ey 2
45-
Tri
met
hyla
nili
nez
24
5-T
rim
ethy
lani
line
HC
lz 2
46-
Tri
met
hyla
nilin
eH
Clz
24
6-T
rini
tro-
13-
dim
ethy
l-5-
tert
-but
ylbe
nzen
eT
ris(
2-ch
loro
ethy
l)ph
osph
atez
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez T
ris(
2-et
hylh
exyl
) pho
spha
tey
Trp
-P-1
acet
atez
Trp
-P-2
acet
atez
Ure
than
ez V
inyl
carb
amat
eV
inyl
uo
ride
z 2
5-X
ylid
ine
HC
lz C
Id
ispe
rse
yell
ow3z
Zea
rale
none
y
Mon
key
8A
ato
xin
B1y
Cyc
asin
and
met
hyla
zoxy
met
hano
lace
tate
IQ
z N
-Nitr
osod
ieth
ylam
ine
N-N
itro
sodi
prop
ylam
ine
N-N
itro
sopi
peri
dine
z S
teri
gmat
ocys
tinz
Ure
than
ez
Rat
206
Ace
tam
idez
Ace
tam
inop
henz
Ace
toxi
me
2-A
cety
lam
ino
uore
nez
A
atox
icol
A
atox
inB
y 1A
at
oxin
cru
dez
1-A
min
o-2
4-di
brom
oant
hraq
uino
nez
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
1-A
min
o-2-
met
hyla
nthr
aqui
none
z 2-
Am
inoa
nthr
aqui
none
z o-
Am
inoa
zoto
luen
ey 11
-Am
inou
ndec
anoi
cac
idy
Ara
mit
ez A
rocl
or12
60A
uram
ine-
Oz
Azo
xym
etha
neB
emit
radi
ne
Ben
zidi
ne3
-Ben
zyls
ydno
ne-4
-ace
tam
idez
Bis
( 23
-dib
rom
opro
pyl)
phos
phat
em
agne
sium
salt
CI
dir
ectb
lue
15
Bro
mod
ichl
orom
etha
nez
Bud
eson
ide
Cap
tafo
lz C
arbo
nte
trac
hlor
idez
Chl
oren
dic
acid
z C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
4-C
hlor
o-4
-am
inod
iphe
nyle
ther
z 2-
Chl
oro-
5-( 3
5-d
imet
hylp
iper
idin
osul
phon
yl) b
enzo
icac
id[
4-C
hlor
o-6-
( 23
-xy
lidi
no) -
2-py
rim
idin
ylth
io] a
ceti
cac
idz
4-C
hlor
o-6-
( 23
-xyl
idin
o)-2
-pyr
imid
inyl
thio
( N-b
-hyd
roxy
ethy
l)ac
etam
idez
Chl
orob
enze
ney
Chl
orof
orm
z 3-
( p-C
hlor
ophe
nyl)
-11
-dim
ethy
lure
ay C
ipro
bra
tez
Cliv
orin
eC
lob
rate
y C
loph
enA
30C
oum
arin
z p-
Cre
sidi
nez
Cro
tona
ldeh
yde
Cup
ferr
onz
Cyc
lope
ntan
one
oxim
eD
DT
z D
ecab
rom
odip
heny
loxi
dey
Deh
ydro
epia
ndro
ster
one
Deh
ydro
epia
ndro
ster
one
acet
ate
24-
Dia
min
otol
uene
z 2
4-D
iam
inot
olue
ne2
HC
lz 1
2-D
ibro
moe
than
ez D
ichl
oroa
ceti
cac
idz
Dic
hlor
oace
tyle
nez
NN
-Die
thyl
-4-(
4-[
pyri
dyl-
1-o
xide
] azo
) ani
line
Die
thyl
stil
best
rolz
Dim
etho
xane
3
3-D
imet
hoxy
benz
idin
e2H
Cl
56-
Dim
etho
xyst
erig
mat
ocys
tinN
N-D
imet
hyl-
4-am
inoa
zobe
nzen
e6-
Dim
ethy
lam
ino-
44-
diph
enyl
-3-h
epta
nola
ceta
teH
Cly
33
-Dim
ethy
lben
zidi
ne2
HC
lz D
imet
hyln
itram
ine
Din
itros
ohom
opip
eraz
ine
26-
Din
itro
tolu
ene
24-
Din
itrot
olue
ne( c
onta
inin
g1
0-1
52
6-di
nitr
otol
uene
)z
Din
itrot
olue
net
echn
ical
grad
e( 2
4( 7
7) -
and
26
( 19
) -)
14-
Dio
xane
z D
ipen
tyln
itro
sam
ine
Dox
ylam
ine
succ
inat
ez E
thin
yles
trad
iol
Eth
ioni
ne
dl-E
thio
nine
z 4-
Eth
oxy-
phen
ylur
eaE
thyl
alco
holy
Z-E
thyl
-ON
N-a
zoxy
etha
neZ
-Eth
yl-O
NN
-azo
xym
etha
neE
thyl
ene
thio
urea
z di
( 2-E
thyl
hexy
l)ph
thal
atez
Flu
cona
zole
y N
-(2-
Flu
oren
yl) -
22
2-tr
iuo
roac
etam
ide
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-t
hiaz
olyl
] hyd
razi
dez
Fum
onis
inB
1F
uran
z Fu
rfur
alz
Glu
-P-1
z G
lu-P
-2z
FDamp
Cgr
een
no1
y H
CD
Dm
ixtu
rez
Hex
achl
orob
enze
nez
a-1
23
45
6-H
exac
hlor
ocyc
lohe
xane
z H
ydra
zine
z H
ydra
zine
sulf
atez
Hyd
razo
benz
enez
Hyd
roch
loro
uor
ocar
bon
123
N-H
ydro
xy-2
-ace
tyla
min
ouo
rene
z 1-
Hyd
roxy
anth
raqu
inon
e1-
( 2-H
ydro
xyet
hyl)
-nitr
oso-
3-ch
loro
ethy
lure
a1
-Hyd
roxy
safr
olez
IQz
IQH
Cl
Ison
iazi
dz K
epon
ez L
asio
carp
ine
MeA
-a-C
acet
atez
MeI
Qxz
Met
hapy
rile
neH
Cl
Z-M
ethy
l-O
NN
-azo
xyet
hane
Met
hylc
arba
mat
ey M
ethy
lclo
fena
pate
z 3
-Met
hyl-
4-di
met
hyla
min
oazo
benz
ene
2-M
ethy
l-1-
nitr
oant
hraq
uino
nez
4-( 4
-N-M
ethy
l-N
-nit
rosa
min
osty
ryl)
quin
olin
e4
4-M
ethy
lene
-bis
( 2-c
hlor
oani
line
) 4
4-M
ethy
lene
-bis
( 2-m
ethy
lani
line
) 4
4-M
ethy
lene
dian
ilin
e2H
Clz
4-( M
ethy
lnit
rosa
min
o)-1
-(3-
pyri
dyl)
-1-(
buta
none
) M
etro
nida
zole
z M
ichl
errsquos
keto
nez
Mir
exz
Mon
ocro
tali
neN
afen
opin
Nit
rite
sod
ium
y N
itrob
enze
nez
2-N
itro
buta
ne2
-Nit
ro
uore
ne3
-Nit
rope
ntan
eN
-Nitr
oso-
bis-
( 44
4-t
ri
uoro
-N-b
utyl
) am
ine
1-N
itros
o-5
6-di
hydr
oura
cil
N-N
itro
so-2
3-d
ihyd
roxy
prop
ylet
hano
lam
ine
1-N
itros
o-1-
hydr
oxye
thyl
-3-c
hlor
oeth
ylur
ea1
-Nitr
oso-
1-( 2
-hyd
roxy
prop
yl) -
3-ch
loro
ethy
lure
aN
-Nitr
oso-
( 2-h
ydro
xypr
opyl
) -( 2
-hyd
roxy
ethy
l)am
ine
N-N
itros
o-N
-met
hyl-
N-d
odec
ylam
ine
Nit
roso
-N-m
ethy
l-N
-(2-
phen
yl) e
thyl
amin
e
( Con
tinue
don
next
page
)
643
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
N-N
itro
so-N
-met
hyld
ecyl
amin
e3-
Nit
roso
-2-o
xazo
lidin
one
Nit
roso
-2-o
xopr
opyl
etha
nola
min
eN
itro
so-1
23
6-t
etra
hydr
opyr
idin
eN
-Nit
roso
ally
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itro
soal
lyl-
2-ox
opro
pyla
min
eN
-Nitr
osoa
llyl
etha
nola
min
eN
-Nit
roso
bis(
2-ox
opro
pyl)
amin
eN
itro
sodi
buty
lam
inez
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
diet
hyla
min
eN
-Nitr
osod
imet
hyla
min
ez p-
Nitr
osod
iphe
nyla
min
ez N
-Nit
roso
dipr
opyl
amin
eN
itros
odod
ecam
ethy
lene
imin
eN
-Nit
roso
ephe
drin
eN
itro
soet
hylm
ethy
lam
ine
Nitr
osoh
epta
met
hyle
neim
ine
N-N
itros
omet
hyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nit
roso
met
hyl-
( 2-h
ydro
xyet
hyl)
amin
eN
-Nitr
osom
ethy
l-( 3
-hyd
roxy
prop
yl) a
min
eN
-Nitr
osom
ethy
l(2-
oxop
ropy
l)am
ine
N-N
itro
som
ethy
l-( 2
-tos
ylox
yeth
yl) a
min
eN
itro
som
ethy
lund
ecyl
amin
eN
-Nit
roso
mor
phol
ine
N-N
itros
opip
erid
inez
N-N
itro
sopy
rrol
idin
ez N
-Nit
roso
thia
ldin
eo-
Nit
roso
tolu
ene
Nor
lest
rinz
N-(
9-O
xo-2
-uo
reny
l)ac
etam
ide
44
-Oxy
dian
iline
z 2
34
56-
Pent
achl
orop
heno
lte
chni
calg
rade
z P
etas
iten
ine
Phe
noba
rbit
als
odiu
mz
1-P
heny
lazo
-2-n
apht
holy
o-P
heny
lene
diam
ine
2HC
lz P
iper
onyl
buto
xide
z P
olyb
rom
inat
edbi
phen
ylm
ixtu
rez
Pre
dnis
olon
eP
yril
amin
em
alea
tey
CI
aci
dre
d11
4C
Ip
igm
entr
ed3z
Damp
Cre
dno
5z
Damp
Cre
dno
9y
FD
ampC
red
no1
p-
Ros
anili
neH
Clz
Saf
role
z Se
leni
umsu
lde
z Se
nkir
kine
Ste
rigm
atoc
ystin
z S
ymph
ytin
eTa
mox
ifen
citr
atez
Telo
neII
tec
hnic
algr
adez
33
44
-Te
traa
min
obip
heny
l4H
Clz
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tetr
auo
roet
hyle
nez
Thi
oace
tam
idez
44
-Thi
odia
nilin
ez To
luen
edi
isoc
yana
te
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
Tri
amci
nolo
neac
eton
ide
24
5-T
rim
ethy
lani
line
z 2
45-
Tri
met
hyla
nili
neH
Clz
24
6-T
rim
ethy
lani
line
HC
lz T
rini
trog
lyce
rin
Trp
-P-1
acet
atez
Trp
-P-2
acet
atez
Vin
ylac
etat
ez V
inyl
brom
ide
Vin
ylch
lori
dez
Vin
yl
uori
dez
CI
dis
pers
eye
llow
3z
Tre
esh
rew
1A
ato
xin
B1y
Lun
gH
amst
er3
Met
hyln
itro
sam
ino-
NN
-dim
ethy
leth
ylam
ine
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
1-N
itro
so-3
45
-tri
met
hylp
iper
azin
eM
ouse
116
Ace
tald
ehyd
em
ethy
lfor
myl
hydr
azon
eN
-Ace
tyl-
4-( h
ydro
xym
ethy
l)ph
enyl
hydr
azin
e1-
Ace
tyl-
2-is
onic
otin
oylh
ydra
zine
A
llyl
hydr
azin
eH
Cl
1-A
min
o-2
4-di
brom
oant
hraq
uino
nez
Are
coli
neH
Cl
5-A
zacy
tidi
nez
Ben
zene
z B
enzo
fura
nz B
enzo
tric
hlor
ide
Ben
zoyl
hydr
azin
eB
enzy
lhyd
razi
ne2
HC
l2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bis
( 2-c
hlor
o-1-
met
hyle
thyl
) eth
er
tech
nica
lgra
dey
Bis
-(ch
loro
met
hyl)
ethe
rz 1
3-B
utad
iene
z N
-n-B
utyl
-N-f
orm
ylhy
draz
ine
But
ylat
edhy
drox
ytol
uene
y 1
1-di
-n-B
utyl
hydr
azin
en-
But
ylhy
draz
ine
HC
l1
2-di
-N-B
utyl
hydr
azin
e2H
Cl
Caf
feic
acid
z C
arba
myl
hydr
azin
eH
Cl
1-C
arba
myl
-2-p
heny
lhyd
razi
neC
hlor
ambu
cilz
Chl
orop
rene
z C
obal
tsul
fate
hept
ahyd
rate
z C
oum
arin
z C
yclo
phos
pham
idez
Dac
arba
zine
z D
amin
ozid
ez p
p-D
DD
y D
DT
z 1
1-D
iall
ylhy
draz
ine
12-
Dia
llyl
hydr
azin
e2H
Cl
Dib
enz(
ah)
anth
race
ne1
2-D
ibro
mo-
3-ch
loro
prop
anez
Dib
rom
odul
cito
lz 1
2-D
ibro
moe
than
ez D
ibro
mom
anni
tolz
12-
Dic
hlor
oeth
anez
12-
Dif
orm
ylhy
draz
ine
Dih
ydro
safr
olez
25-
Dim
etho
xy-4
-am
inos
tilbe
nez
33
-Dim
ethy
lben
zidi
ne2
HC
lz 1
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
a-E
cdys
one
Est
radi
olm
usta
rdy
N-E
thyl
-N-f
orm
ylhy
draz
ine
Eth
ylen
eim
ine
Eth
ylen
eox
idez
Eth
ylhy
draz
ine
HC
l5-
Flu
orou
raci
ly Fo
rmyl
hydr
azin
eG
lyci
dolz
c-1
23
45
6-H
exac
hlor
ocyc
lohe
xane
y H
exan
alm
ethy
lfor
myl
hydr
azon
eH
ydra
zine
z H
ydra
zine
sulf
atez
IQz
Isob
utyl
nitr
itez
Ison
iazi
dz Is
onic
otin
icac
idva
nilly
liden
ehyd
razi
de
Isop
rene
Lov
asta
tinM
eIQ
xz M
elph
alan
z 1-
Met
hyl-
14-
dihy
dro-
7-[ 2
-(5-
nitr
ofur
yl) v
inyl
] -4-
oxo-
18-
naph
thyr
idin
e-3-
carb
oxyl
ate
pota
ssiu
m
N-M
ethy
l-N
-for
myl
hydr
azin
eM
ethy
lmet
hane
sulf
onat
e3-
Met
hylb
utan
alm
ethy
lfor
myl
hydr
azon
eM
ethy
lene
chlo
ride
z M
ethy
lhyd
razi
ne
Met
hylh
ydra
zine
sulf
ate
( N-6
) -( M
ethy
lnit
roso
) ade
nine
(N
-6) -
( Met
hyln
itro
so) a
deno
sine
N-M
ethy
lola
cryl
amid
ey M
etro
nida
zole
z M
olyb
denu
mtr
ioxi
dey
Mon
oace
tylh
ydra
zine
Nap
htha
lene
15
-Nap
htha
lene
diam
inez
Nic
otin
icac
idhy
draz
ide
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez 3-
Nitr
o-3-
hexe
nez
Nit
robe
nzen
ez N
itrom
etha
nez
Nit
roso
dibu
tyla
min
ez N
-Nit
roso
dim
ethy
lam
inez
N-N
itros
ohex
amet
hyle
neim
ine
N-N
itro
sopi
peri
dine
z O
zone
y Pe
ntan
alm
ethy
lfor
myl
hydr
azon
en-
Pen
tylh
ydra
zine
HC
lPh
enes
teri
nz Ph
enyl
ethy
lhyd
razi
nesu
lfat
eP
roca
rbaz
ine
HC
lz N
-N-P
ropy
l-N
-for
myl
hydr
azin
eP
ropy
lhyd
razi
neH
Cl
Sel
eniu
msu
lde
z S
trep
tozo
toci
nz Su
lfal
late
z Te
lone
IIt
echn
ical
grad
ez 3
34
4-T
etra
amin
obip
heny
l4H
Clz
Tetr
anitr
omet
hane
z T-
2to
xin
Tri
chlo
roet
hyle
nez
Tri
ura
lint
echn
ical
grad
ey 2
45-
Tri
met
hyla
nilin
eH
Clz
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez U
reth
anez
Vin
ylch
lori
dez
Vin
ylu
orid
ez V
inyl
iden
ech
lori
dey
24-
Xyl
idin
eH
Cly
Mon
key
1U
reth
anez
Rat
551-
Ally
l-1-
nitr
osou
rea
2-A
min
o-5-
( 5-n
itro
-2-f
uryl
) -1
34-
oxad
iazo
le2
-Am
ino-
5-( 5
-nitr
o-2-
fury
l)-1
34
-thi
adia
zole
2-A
min
o-5-
nitr
othi
azol
ey 1-
Am
yl-1
-nitr
osou
rea
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
is-(
chlo
rom
ethy
l)et
herz
HC
blue
no1
z B
rom
oeth
anez
N-n
-But
yl-N
-nit
roso
urea
Cad
miu
mch
lori
deC
adm
ium
sulp
hate
( 11
) 1-
Chl
oroe
thyl
nitr
oso-
3-( 2
-hyd
roxy
prop
yl) u
rea
Chl
orop
rene
z C
obal
tsul
fate
hept
ahyd
rate
z 1
2-D
ibro
moe
than
ez D
imet
hylh
ydro
gen
phos
phit
ey tr
ans-
2-[(
Dim
ethy
lam
ino)
met
hylim
ino]
-5-
[ 2-(
5-ni
tro-
2-fu
ryl)
viny
l] -1
34-
oxad
iazo
le3
3-D
imet
hylb
enzi
dine
2H
Clz
12-
Epo
xybu
tane
y 1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
N-H
exyl
nitr
osou
rea
Hyd
razi
nez
Hyd
razi
nesu
lfat
ez 1-
( 2-H
ydro
xyet
hyl)
-1-n
itro
sour
eaz
Isob
utyl
nitr
itez
Ison
iazi
dz 4
4-M
ethy
lene
-bi
s(2-
chlo
roan
iline
) 4-
( Met
hyln
itros
amin
o)-1
-(3-
pyri
dyl)
-1-b
utan
ol4
-(M
ethy
lnit
rosa
min
o)-1
-(3-
pyri
dyl)
-1-(
buta
none
) N
-[ 3
-(5-
Nitr
o-2-
fury
l)-
12
4-ox
adia
zole
-5-y
l] -m
ethy
lace
tam
ide
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
3-N
itro-
3-he
xene
z 5-
Nitr
oace
naph
then
ez N
-Nit
roso
-bis
-(4
44-
tri
uoro
-N-b
utyl
) am
ine
N-N
itros
o-N
-met
hyl-
N-d
odec
ylam
ine
N-N
itros
o-N
-met
hyl-
N-t
etra
decy
lam
ine
N-N
itro
so-N
-met
hyld
ecyl
amin
eN
-Nitr
oso-
N-m
ethy
lure
az N
-Nitr
osob
is( 2
-hyd
roxy
prop
yl)
amin
eN
-Nitr
osob
is-2
3-d
ihyd
roxy
prop
ylam
ine
( 2-o
xopr
opyl
) am
ine
Nitr
osod
ibut
ylam
inez
N-N
itros
odim
ethy
lam
inez
N-N
itro
soep
hedr
ine
Nitr
osoe
thyl
met
hyla
min
eN
-Nit
roso
met
hyl
N-N
itro
som
ethy
l-( 3
-hyd
roxy
prop
yl) a
min
eN
itro
som
ethy
lund
ecyl
amin
eC
Ia
cid
red
114
Sod
ium
dich
rom
ate
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tetr
anit
rom
etha
nez
24
5-T
rim
ethy
lani
line
z 2
46-
Tri
met
hyla
nili
neH
Clz
Vin
ylch
lori
dez
Mam
mar
ygl
and
Dog
1Ly
nest
reno
lH
amst
er1
Vin
ylch
lori
dez
Mou
se24
5-A
zacy
tidin
ez B
enze
nez
CI
dir
ectb
lack
381
3-B
utad
iene
z C
alci
fero
lC
hlor
opre
nez
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
Die
thyl
stilb
estr
olz
a-E
cdys
one
Est
radi
olE
thyl
ene
oxid
ez F
uros
emid
ey G
lyci
dolz
Gri
seof
ulvi
nIs
onia
zidz
Ison
icot
inic
acid
vani
llylid
eneh
ydra
zide
( N
-6) -
( Met
hyln
itros
o)ad
enos
ine
Nitr
oben
zene
z R
eser
pine
z Su
lfal
late
z V
inyl
chlo
ride
z V
inyl
uor
idez
Vin
ylid
ene
chlo
ride
y
644
Rat
102
4-A
cety
lam
inob
iphe
nyl
2-A
cety
lam
ino
uore
nez
Acr
onyc
ine
Acr
ylam
ide
Acr
ylon
itri
leA
F-2
z 1-
Ally
l-1-
nitr
osou
rea
2-A
min
o-5-
( 5-n
itro-
2-fu
ryl)
-13
4-
oxad
iazo
le2
-Am
ino-
5-( 5
-nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
e2-
Am
ino-
5-ni
trot
hiaz
oley
4-A
min
odip
heny
lHC
l1-
Am
yl-1
-nit
roso
urea
Atr
azin
ey B
emit
radi
ne
Ben
zidi
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
4-B
is( 2
-hyd
roxy
ethy
l)am
ino-
2-( 5
-nit
ro-2
-thi
enyl
) qui
nazo
line
13-
But
adie
nez
N-n
-But
yl-N
-nitr
osou
rea
Cap
tafo
lz C
arbo
nte
trac
hlor
idez
Car
boxy
met
hyln
itros
oure
aC
hlor
ambu
cilz
Chl
orop
rene
z C
ytem
bena
y D
acar
bazi
nez
N-1
-Dia
ceta
mid
ouo
rene
46
-Dia
min
o-2-
( 5-n
itro-
2-fu
ryl)
-S-t
riaz
ine
24-
Dia
min
oani
sole
sulf
atez
24-
Dia
min
otol
uene
z 1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dib
rom
oman
nito
lz 1
3-D
ibut
yl-1
-nit
roso
urea
33
-Dic
hlor
oben
zidi
ne1
2-D
ichl
oroe
than
ez 3
3-D
imet
hoxy
benz
idin
e2H
Cl
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
12-
Dim
ethy
l-5-
nitr
oim
idaz
ole
tran
s-2-
[(D
imet
hyla
min
o)m
ethy
limin
o]-5
-[2-
( 5-n
itro
-2-f
uryl
) vin
yl] -
13
4-ox
adia
zole
Dim
ethy
lam
inoe
thyl
nitr
osoe
thyl
urea
nitr
ite
salt
33
-Dim
ethy
lben
zidi
ne2
HC
lz 2-
( 22
-Dim
ethy
lhyd
razi
no) -
4-( 5
-nitr
o-2-
fury
l)th
iazo
le
24-
Din
itro
tolu
ene
( con
tain
ing
10-
15
24-
Dio
xane
z 1-
Eth
ylni
tros
o-3-
( 2-h
ydro
xyet
hyl)
-ure
a1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
6-di
nitr
otol
uene
)zN
-(2-
Fluo
reny
l)-2
22
-tri
uo
roac
etam
ide
Form
icac
id2-
( 4-m
ethy
l-2-
thia
zoly
l)hy
draz
ide
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-
thia
zoly
l] hyd
razi
dez
Gly
cido
lz H
exam
ethy
lmel
amin
eN
-Hex
ylni
tros
oure
a2-
Hyd
razi
no-4
-(p-
amin
ophe
nyl)
thia
zole
z 2-
Hyd
razi
no-4
-( 5
-nit
ro-2
-fur
yl) t
hiaz
olez
2-H
ydra
zino
-4-(
p-ni
trop
heny
l)th
iazo
lez
Hyd
razo
benz
enez
1-( 2
-Hyd
roxy
ethy
l)-3
-[( 5
-nit
rofu
rfur
ylid
ene)
amin
o]-2
-im
idaz
olid
inon
e1-
( 2-H
ydro
xyet
hyl)
-nit
roso
-3-e
thyl
urea
1-(
2-H
ydro
xyet
hyl)
-1-n
itros
oure
az In
dom
etha
cin
IQz
IQH
Cl
Ison
iazi
dz 2-
Met
hoxy
-3-a
min
odib
enzo
fura
n4-
Met
hyl-
1-[(
5-ni
trof
urfu
rylid
ene)
amin
o]-2
-im
idaz
olid
inon
eN
-(N
-Met
hyl-
N-n
itro
soca
rbam
oyl)
-l-o
rnit
hine
3-M
ethy
lcho
lant
hren
e4
4-M
ethy
lene
-bi
s(2-
chlo
roan
iline
) 4
4-M
ethy
lene
-bis
( 2-m
ethy
lani
line)
Met
hyle
nech
lori
dez
Met
roni
dazo
lez
l-5-
Mor
phol
inom
ethy
l-3-
[(5-
nitr
ofur
fury
lide
ne) a
min
o]-
2-ox
azol
idin
one
HC
lN
ithia
zide
z 5-
Nitr
o-2-
fura
ldeh
yde
sem
icar
bazo
nez
3-( 5
-Nitr
o-2-
fury
l)-i
mid
azo(
12-
a)
pyri
dine
z 4-
( 5-N
itro-
2-fu
ryl)
thia
zole
N
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] ace
tam
ide
NN
-[6-
( 5-N
itro
-2-f
uryl
) -S-
tria
zine
-24
-diy
l] bis
acet
amid
e5-
Nitr
oace
naph
then
ez 1-
[(5-
Nit
rofu
rfur
ylid
ene)
amin
o]-2
-im
idaz
olid
inon
eN
itrom
etha
nez
1-N
itrop
yren
eN
orle
stri
nz O
chra
toxi
nA
z N
-(9-
Oxo
-2-
uore
nyl)
acet
amid
ePh
enac
etin
z Ph
enes
teri
nz Ph
IPH
Clz
Proc
arba
zine
HC
lz Pr
opan
esu
lton
e1
2-Pr
opyl
ene
oxid
ez St
yren
ey Su
lfal
late
z 4
4-S
ulfo
nylb
isac
etan
ilid
eTo
luen
edi
isoc
yana
te
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
o-T
olui
dine
HC
lz 1
23-
Tri
chlo
ropr
opan
ez 2
22-
Tri
uor
o-N
-[4-
( 5-n
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] ace
tam
idez
Trp
-P-2
acet
atez
Vin
ylch
lori
dez
FD
ampC
viol
etno
1y
Mes
ovar
ium
Rat
2Sa
lbut
amol
Ter
buta
line
Myo
card
ium
Mou
se2
Est
radi
olm
usta
rdy
Phen
este
rinz
Nas
alca
vity
bB
ush
baby
1N
-Nitr
osod
ieth
ylam
ine
Ham
ster
11A
ceta
ldeh
yde
Dia
llyln
itros
amin
eD
imet
hylc
arba
myl
chlo
ride
Hyd
razi
nez
Met
hyln
itro
sam
ino-
NN
-dim
ethy
leth
ylam
ine
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
N-N
itro
soal
lyl-
2-ox
opro
pyla
min
eN
-Nitr
osom
ethy
l-2
3-di
hydr
oxyp
ropy
lam
ine
N-N
itros
omor
phol
ine
N-N
itros
onor
nico
tine
N-N
itros
opip
erid
inez
Mou
se6
Ally
lgly
cidy
leth
ery
12-
Dib
rom
o-3-
chlo
ropr
opan
ez 1
2-D
ibro
moe
than
ez Fo
rmal
dehy
dez
N-N
itro
sohe
xam
ethy
lene
imin
e1
2-Pr
opyl
ene
oxid
ez
Rat
43A
ceta
ldeh
yde
Acr
ylon
itril
e1-
Azo
xypr
opan
eB
enze
nez
Bis
-(ch
loro
met
hyl)
ethe
rz p-
Cre
sidi
nez
Dia
llyln
itros
amin
e1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dim
ethy
lnitr
amin
eD
imet
hylv
inyl
chlo
ride
z D
initr
osoh
omop
iper
azin
e1
4-D
ioxa
nez
12-
Epo
xybu
tane
y Z
-Eth
yl-O
NN
-azo
xyet
hane
E
thyl
benz
ene
Eth
ylni
tros
ocya
nam
ide
Form
alde
hyde
z H
exam
ethy
lpho
spho
ram
ide
Hyd
razi
nez
N-N
itro
so-N
-met
hyld
ecyl
amin
edi
( N-N
itro
so) -
perh
ydro
pyri
mid
ine
N-N
itros
o(2
22-
tri
uoro
ethy
l)et
hyla
min
e1-
Nitr
oso-
34
5-tr
imet
hylp
iper
azin
eN
-Nitr
osoa
llyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nit
roso
ally
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itro
soal
lyle
than
olam
ine
N-N
itros
obis
( 2-h
ydro
xypr
opyl
) am
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
dipr
opyl
amin
eN
itros
oeth
ylm
ethy
lam
ine
N-N
itros
omet
hyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nitr
osom
ethy
l-( 2
-hyd
roxy
ethy
l)am
ine
N-N
itro
som
ethy
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itros
omet
hyl(
2-ox
opro
pyl)
amin
eN
-Nit
roso
norn
icot
ine-
1-N
-oxi
de
N-N
itro
sopi
peri
dine
z P
hena
cetin
z Ph
enyl
glyc
idyl
ethe
r1
2-Pr
opyl
ene
oxid
ez V
inyl
acet
atez
Vin
ylch
lori
dez
Ner
vous
Mou
se3
13-
But
adie
nez
N-N
itros
odim
ethy
lam
inez
Pro
carb
azin
eH
Clz
syst
emR
at21
Acr
ylam
ide
Acr
ylon
itril
eB
rom
oeth
anez
Chl
oram
buci
lz 1-
( 4-C
hlor
ophe
nyl)
-1-p
heny
l-2-
prop
ynyl
carb
amat
eC
yclo
phos
pham
idez
1-E
thyl
-1-n
itros
oure
aE
thyl
eneo
xide
z 1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
eaG
lu-P
-1z
Glu
-P-2
z G
lyci
dolz
R(
) -2-
Met
hyl-
N-n
itro
sopi
peri
dine
S(
) -2-
Met
hyl-
N-n
itro
sopi
peri
dine
M
ethy
lnit
ram
ine
N-N
itros
o-N
-met
hylu
reaz
N-N
itros
odie
than
olam
ine
1-P
heny
l-3
3-di
met
hyltr
iaze
neP
roca
rbaz
ine
HC
lz P
ropa
nesu
ltone
Vin
ylch
lori
dez
Ora
lcav
ityc
Ham
ster
4A
ceta
ldeh
yde
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
N-N
itros
omor
phol
ine
N-N
itro
sopi
peri
dine
z
Mou
se3
N-N
itros
ohex
amet
hyle
neim
ine
12
3-T
rich
loro
prop
anez
Vin
ylac
etat
ez
Rat
32A
cryl
amid
eA
cryl
onitr
ile
Ben
zene
z 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
CI
dir
ectb
lue
15C
Id
irec
tblu
e21
8z C
hlor
opre
nez
3-D
iazo
tyra
min
eH
Cl
12-
Dib
rom
o-3-
chlo
ropr
opan
ez 3
3-D
imet
hoxy
benz
idin
e2H
Cl
33
-Dim
ethy
lben
zidi
ne2
HC
lz D
imet
hylv
inyl
chlo
ride
z D
initr
osoh
omop
iper
azin
eG
lyci
dolz
IQz
MeA
-a-C
acet
atez
N-N
itros
o-2
3-di
hydr
oxyp
ropy
l-2-
hydr
oxyp
ropy
lam
ine
Nit
roso
-23
-dih
ydro
xypr
opyl
-2-
oxop
ropy
lam
ine
Nitr
oso-
N-m
ethy
l-N
-(2-
phen
yl) e
thyl
amin
eN
itro
soam
ylur
etha
nN
-Nitr
osod
ieth
ylam
ine
Nit
roso
ethy
lure
than
N
itros
ohep
tam
ethy
lene
imin
e1-
Nitr
osoh
ydan
toin
N-N
itros
omet
hyl(
2-ox
opro
pyl)
amin
eN
-Nit
roso
thia
ldin
eN
-Nitr
osot
hiom
orph
olin
eC
Ia
cid
red
114
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tolu
eney
12
3-T
rich
loro
prop
anez
Xyl
ene
mix
ture
( m-x
ylen
eo-
xyle
nep
-xyl
ene)
Ova
ryM
ouse
10B
enze
nez
13-
But
adie
nez
Die
thyl
stil
best
rolz
N-M
ethy
lola
cryl
amid
ey 5-
Nitr
o-2-
fura
ldeh
yde
sem
icar
bazo
nez
5-N
itroa
cena
phth
enez
1-[(
5-N
itro
furf
uryl
iden
e)am
ino]
hyda
ntoi
nz P
heno
lpht
hale
inz
Tam
oxif
enci
trat
ez 4-
Vin
ylcy
cloh
exen
ePa
ncre
asH
amst
er3
Nitr
oso-
23-
dihy
drox
ypro
pyl-
2-ox
opro
pyla
min
eN
itro
so-2
6-d
imet
hylm
orph
olin
eN
itro
so-2
-oxo
prop
ylet
hano
lam
ine
Mon
key
1U
reth
anez
Rat
222-
Am
ino-
5-ni
trop
heno
ly 1-
( Am
inom
ethy
l)cy
cloh
exan
eace
ticac
idA
zase
rine
But
ylbe
nzyl
phth
alat
ey C
hlor
endi
cac
idz
Cin
nam
ylan
thra
nila
tez
Clo
bra
tey
Dic
hlor
vosz
Eth
ylal
coho
ly H
ydro
chlo
ro
uoro
carb
on12
3IQ
HC
lM
alon
alde
hyde
sod
ium
saltz
MeA
-a-C
acet
atez
2-M
erca
ptob
enzo
thia
zole
y M
ethy
lclo
fena
pate
z N
-(N
-Met
hyl-
N-n
itros
ocar
bam
oyl)
-l-o
rnit
hine
4-(
Met
hyln
itro
sam
ino)
-1-(
3-py
ridy
l)-1
-but
anol
4-(
Met
hyln
itros
amin
o)-1
-( 3
-pyr
idyl
) -1-
( but
anon
e)N
afen
opin
Nitr
ofen
z To
luen
edi
isoc
yana
tec
omm
erci
algr
ade
( 24
( 80
) -an
d2
6( 2
0) -
)z1
23
-Tri
chlo
ropr
opan
ez
Peri
tone
alM
ouse
8B
is-1
2-(
chlo
rom
etho
xy) e
than
eB
is-1
4-(
chlo
rom
etho
xy) -
p-xy
lene
Bis
-(ch
loro
met
hyl)
ethe
rz C
hlor
opre
nez
tran
s-1
4-D
ichl
orob
uten
e-2
cavi
tyD
imet
hylc
arba
myl
chlo
ride
Phe
noxy
benz
amin
eH
Clz
Tri
s-1
23-
( chl
orom
etho
xy) p
ropa
neR
at22
Acr
onyc
ine
Acr
ylam
ide
Act
inom
ycin
DA
nili
neH
Cly
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
rom
ate
pota
ssiu
mz
Chl
oroz
otoc
in
Cyt
embe
nay
Dap
sone
y 1
2-D
ibro
moe
than
ez D
ibro
mom
anni
tolz
33
-Dim
ethy
lben
zidi
ne2
HC
lz 1
4-D
ioxa
nez
Eth
ylen
eox
idez
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Gly
cido
lz M
elph
alan
z N
-Met
hyl-
N4
-din
itros
oani
line
Mit
omyc
in-C
N-N
itro
so-2
24
-tri
met
hyl-
12-
dihy
droq
uino
line
poly
mer
Ph
enox
yben
zam
ine
HC
lz o-
Tolu
idin
eH
Clz
( Con
tinue
don
next
page
)
645
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Pitu
itar
ygl
and
Mou
se8
Die
thyl
stil
best
rolz
Eno
vid
Eth
ylen
eth
iour
eaz
Iodi
nate
dgl
ycer
olz
Isop
rene
Nor
lest
rinz
Pro
pylt
hiou
raci
lz Z
eara
leno
ney
Rat
73-
Am
inot
riaz
olez
12-
Dib
rom
oeth
anez
Die
thyl
stil
best
rolz
Eth
ylal
coho
ly 2-
Mer
capt
oben
zoth
iazo
ley
Met
roni
dazo
lez
Nor
lest
rinz
Pros
tate
Rat
4C
adm
ium
chlo
ride
N-N
itros
obis
( 2-h
ydro
xypr
opyl
) am
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
PhIP
HC
lz
Skin
Ham
ster
2U
reth
anez
Vin
ylch
lori
dez
Mou
se5
5-A
zacy
tidin
ez 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Chl
orop
rene
z G
lyci
dolz
Thi
o-te
paz
Rat
332-
Ace
tyla
min
ouo
rene
z 3-
Am
ino-
9-et
hylc
arba
zole
mix
ture
z 1-
Azo
xypr
opan
e2-
Azo
xypr
opan
eB
enze
nez
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
ol
tech
nica
lgra
dez
CI
dir
ectb
lue
15C
arbo
xym
ethy
lnitr
osou
rea
24-
Dia
min
oani
sole
sulf
atez
Dib
rom
odul
cito
lz D
ibro
mom
anni
tolz
Dim
etho
xane
2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 3
3-D
imet
hoxy
benz
idin
e-4
4-d
iisoc
yana
tey
33
-Dim
etho
xybe
nzid
ine
2HC
l3
3-D
imet
hylb
enzi
dine
2H
Clz
Dim
ethy
lvin
ylch
lori
dez
24-
Din
itro
tolu
ene
( con
tain
ing
10-
15
26-
dini
trot
olue
ne)z
1-E
thyl
nitr
oso-
3-( 2
-hyd
roxy
ethy
l)-u
rea
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Gly
cido
lz 1-
( 2-H
ydro
xyet
hyl)
-nit
roso
-3-e
thyl
urea
IQ
z L
asio
carp
ine
MeI
Qxz
N-(
N-M
ethy
l-N
-nitr
osoc
arba
moy
l)-l
-orn
ithi
ne
5-N
itro-
o-an
isid
inez
CI
aci
dre
d11
4p-
Ros
anili
neH
Clz
Thi
o-te
paz
Thi
oure
ay V
inyl
chlo
ride
z F
Damp
Cvi
olet
no1
y
Smal
lint
esti
neM
ouse
6C
apta
folz
Cap
tanz
N-E
thyl
-N-n
itro
-N-n
itro
sogu
anid
ine
Hyd
roge
npe
roxi
deN
-Met
hyl-
N-n
itro-
N-n
itros
ogua
nidi
nez
N-(
Tri
chlo
rom
ethy
lthi
o)ph
thal
imid
eM
onke
y1
Ure
than
ez
Rat
29A
cryl
onitr
ile
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
is( 2
3-d
ibro
mop
ropy
l)ph
osph
ate
mag
nesi
umsa
lt4
-Bis
( 2-h
ydro
xyet
hyl)
amin
o-2-
( 5-n
itro
-2-t
hien
yl) q
uina
zolin
eC
Id
irec
tblu
e15
Car
boxy
met
hyln
itros
oure
a1-
( 4-C
hlor
ophe
nyl)
-1-p
heny
l-2-
prop
ynyl
carb
amat
e2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 3
3-D
imet
hoxy
benz
idin
e2H
Cl
46-
Dim
ethy
l-2-
( 5-n
itro
-2-f
uryl
)py
rim
idin
etr
ans-
2-[(
Dim
ethy
lam
ino)
met
hylim
ino]
-5-[
2-( 5
-nit
ro-2
-fur
yl) v
inyl
] -1
34-
oxad
iazo
le3
3-D
imet
hylb
enzi
dine
2H
Clz
Z-E
thyl
-ON
N-a
zoxy
met
hane
1-E
thyl
-1-n
itros
oure
aFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z G
lu-P
-1z
Glu
-P-2
z IQ
z L
asio
carp
ine
N-M
ethy
l-N
-nitr
o-N
-nitr
osog
uani
dine
z N
-[5-
( 5-N
itro-
2-fu
ryl)
-13
4-t
hiad
iazo
l-2-
yl] a
ceta
mid
ez N
-Nitr
oso-
N-i
sobu
tylu
rea
3-N
itro
so-2
-oxa
zoli
dino
neN
itro
soet
hylu
reth
ane
PhI
PH
Clz
Pro
pane
sulto
neQ
uerc
etin
y C
Ia
cid
red
114
Trp
-P-2
acet
atez
Sple
enR
at7
Ani
line
HC
ly A
zobe
nzen
ey p-
Chl
oroa
nili
neH
Clz
Dap
sone
y o-
Nitr
osot
olue
neD
ampC
red
no9
y o-
Tolu
idin
eH
Clz
Stom
ach
Ham
ster
18A
F-2z
14-
Din
itros
o-2
6-di
met
hylp
iper
azin
eFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z H
ydra
zine
z N
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
N-[
4-( 5
-Nitr
o-2-
fury
l)-2
-thi
azol
yl] a
ceta
mid
eN
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] for
mam
idez
N-N
itro
so-2
3-d
ihyd
roxy
prop
yl-2
-hyd
roxy
prop
ylam
ine
Nitr
oso-
23-
dihy
drox
ypro
pyl-
2-ox
opro
pyla
min
eN
-Nitr
oso-
ethy
l-2-
oxop
ropy
lure
aN
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aN
itros
o-5-
met
hylo
xazo
lidon
eN
-Nit
roso
-N-m
ethy
lure
than
N-N
itros
o-1
3-ox
azol
idin
eN
-Nit
roso
-2-p
heny
leth
ylur
ea1
-Nit
roso
-34
5-t
rim
ethy
lpip
eraz
ine
Ure
than
ez V
inyl
chlo
ride
z
Mou
se63
Ace
tald
ehyd
em
ethy
lfor
myl
hydr
azon
eA
ciu
orfe
nA
F-2
z 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 2-
Am
ino-
4-( 5
-nitr
o-2-
fury
l)th
iazo
lez
tran
s-5-
Am
ino-
3[2-
( 5-n
itro-
2-fu
ryl)
viny
l] -1
24-
oxad
iazo
leA
reco
line
HC
lB
enza
ldeh
ydey
Ben
zofu
ranz
Ben
zotr
ichl
orid
eB
enzy
lace
tate
y B
enzy
lchl
orid
ey B
rom
oeth
anol
13
-But
adie
nez
But
ylat
edhy
drox
yani
sole
z 1
1-di
-N-B
utyl
hydr
azin
eC
affe
icac
idz
Cap
tafo
lz C
arba
zole
Cat
echo
lz 3-
Chl
oro-
2-m
ethy
lpro
pene
tec
hnic
algr
ade
( con
tain
ing
5di
met
hylv
inyl
chlo
ride
)z3
-(C
hlor
omet
hyl)
pyri
dine
HC
lz C
hlor
opre
nez
2-C
hlor
opro
pana
l1-
Chl
orop
rope
neC
ypro
tero
neac
etat
e1
1-D
ially
lhyd
razi
ne1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dic
hlor
vosz
Dig
lyci
dylr
esor
cino
leth
ert
echn
ical
grad
ez D
imet
hylv
inyl
chlo
ride
z D
init
roso
pipe
razi
neE
stra
diol
mus
tard
y E
thyl
acry
late
z Fo
rmic
acid
2-[ 4
-( 5
-nit
ro-2
-fur
yl) -
2-th
iazo
lyl] h
ydra
zide
z G
lyci
dolz
2-H
ydra
zino
-4-(
5-ni
tro-
2-fu
ryl)
thia
zole
z N
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
ICI
1628
46z
IQz
Isop
rene
Lov
asta
tin
MeI
Q1
-Met
hyl-
14-
dihy
dro-
7-[ 2
-(5-
nitr
ofur
yl) v
inyl
] -4-
oxo-
18-
naph
thyr
idin
e-3-
carb
oxyl
ate
pota
ssiu
m3
-(5-
Nitr
o-2-
fury
l)-
imid
azo(
12-
a) p
yrid
inez
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
N-[
4-( 5
-Nitr
o-2-
fury
l)-2
-thi
azol
yl] f
orm
amid
ez N
-Nit
roso
-N
-met
hylu
reaz
Nit
roso
dibu
tyla
min
ez N
-Nit
roso
hexa
met
hyle
neim
ine
N-N
itros
opip
erid
inez
b-P
ropi
olac
tone
z Se
sam
olz
Sty
rene
oxid
ez Te
lone
IIt
echn
ical
grad
ez N
-(T
rich
loro
met
hylth
io) p
htha
limid
e1
23-
Tri
chlo
ropr
opan
ez 2
22-
Tri
uo
ro-N
-[4-
( 5-n
itro
-2-f
uryl
) -2-
thia
zoly
l]ac
etam
idez
Tri
ur
alin
tec
hnic
algr
adey
Tri
s(2-
chlo
roet
hyl)
phos
phat
ez T
ris(
23-
dibr
omop
ropy
l)ph
osph
atez
Vin
ylac
etat
ez
Rat
85A
ceto
ne[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zone
1-A
ceto
xysa
frol
ey A
cryl
onitr
ile
1-A
llyl
-1-n
itro
sour
ea2
-Am
ino-
5-( 5
-nit
ro-2
-fur
yl) -
13
4-ox
adia
zole
2-
Am
ino-
5-( 5
-nitr
o-2-
fury
l)-1
34
-thi
adia
zole
2-A
min
o-4-
( 5-n
itro
-2-f
uryl
) thi
azol
ez 1-
Am
yl-1
-nit
roso
urea
Ari
stol
ochi
cac
id
sodi
umsa
lt( 7
7A
AI
21
AA
II)
Ben
zene
z B
enzo
( a) p
yren
ez 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bis
( 23
-dib
rom
opro
pyl)
phos
phat
em
agne
sium
salt
BL
-634
1H
Cl
N-n
-But
yl-N
-nitr
osou
rea
But
ylat
edhy
drox
yani
sole
z b
-But
yrol
acto
neC
affe
icac
idz
Cat
echo
lz 3-
Chl
oro-
2-m
ethy
lpro
pene
tec
hnic
algr
ade
( con
tain
ing
5di
met
hylv
inyl
chlo
ride
)z4
-Chl
oro-
o-ph
enyl
ened
iam
inez
Chl
oro
uoro
met
hane
3-
( Chl
orom
ethy
l)py
ridi
neH
Clz
Cip
rob
rate
z C
upfe
rron
z 1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
Dig
lyci
dylr
esor
cino
leth
ert
echn
ical
grad
ez 2
5-D
imet
hoxy
-4-a
min
osti
lben
ez D
imet
hylh
ydro
gen
phos
phit
ey 4
6-D
imet
hyl-
2-( 5
-nit
ro-2
-fu
ryl)
pyri
mid
ine
tran
s-2-
[(D
imet
hyla
min
o)m
ethy
limin
o]-5
-[2-
( 5-n
itro
-2-f
uryl
) vin
yl] -
13
4-ox
adia
zole
Dim
ethy
lvin
ylch
lori
dez
Epi
chlo
rohy
drin
y E
thyl
acry
late
z E
thyl
ene
oxid
ez 2-
Flu
oroe
thyl
-nitr
osou
rea
Gly
cido
lz N
-Hex
ylni
tros
oure
a1-
Hyd
roxy
anth
raqu
inon
e1-
( 2-H
ydro
xyet
hyl)
-1-
nitr
osou
reaz
1-( 3
-Hyd
roxy
prop
yl) -
1-ni
tros
oure
a1
-Hyd
roxy
safr
olez
ICI
1628
46z
Lox
tidin
eL
upit
idin
e3H
Cl
Mer
curi
cch
lori
dey
3-M
etho
xyca
tech
ol4
-Met
hoxy
phen
olN
-Met
hyl-
N-n
itro-
N-n
itros
ogua
nidi
nez
N-M
ethy
l-N
-nit
roso
benz
amid
e4-
Met
hylc
atec
hol
Met
hyln
itro
socy
anam
ide
3-( 5
-Nit
ro-2
-fur
yl) -
imid
azo(
12-
a) p
yrid
inez
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
4-( 5
-Nit
ro-2
-fur
yl) t
hiaz
ole
2-N
itro
uo
rene
8-N
itro
quin
olin
eN
itro
so-B
aygo
nN
-Nit
roso
-23
-dih
ydro
xypr
opyl
-2-h
ydro
xypr
opyl
amin
eN
itros
o-2
3-di
hydr
oxyp
ropy
l-2-
oxop
ropy
lam
ine
1-N
itro
so-3
5-d
imet
hyl-
4-be
nzoy
lpip
eraz
ine
N-N
itro
so-N
-met
hyl-
N-d
odec
ylam
ine
Nitr
oso-
N-m
ethy
l-N
-(2-
phen
yl) e
thyl
amin
eN
-Nit
roso
-N-m
ethy
ldec
ylam
ine
N-N
itro
so-N
-met
hylu
reaz
Nit
roso
-12
36
-tet
rahy
drop
yrid
ine
N-N
itro
sobe
nzth
iazu
ron
Nitr
osod
ibut
ylam
inez
N-N
itros
odie
thyl
amin
eN
-Nit
roso
ephe
drin
eN
itros
oeth
ylur
etha
nO
mep
razo
ley
Phen
acet
inz
Piv
alol
acto
ney
b-P
ropi
olac
tone
z N
-Pro
pyl-
N-n
itro
-N-n
itro
sogu
anid
ine
12-
Pro
pyle
neox
idez
Ses
amol
z St
yren
eox
idez
Sulf
alla
tez
Telo
neII
tec
hnic
algr
adez
12
3-T
rich
loro
prop
anez
24
6-T
rim
ethy
lani
line
HC
lz
646
Subc
utan
eous
Mou
se4
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 1
2-D
ibro
moe
than
ez N
2-c
-Glu
tam
yl-p
-hyd
razi
nobe
nzoi
cac
idG
lyci
dolz
tissu
eR
at13
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 2
4-D
iam
inot
olue
ne2
HC
lz 1
2-D
ichl
oroe
than
ez D
imet
hoxa
ne1
4-D
ioxa
nez
MeA
-a-C
acet
atez
44
-Met
hyle
ne-b
is( 2
-met
hyla
nili
ne)
o-N
itro
soto
luen
ep-
Ros
anili
neH
Clz
Tolu
ene
diis
ocya
nate
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
o-T
olui
dine
HC
lz 2
45-
Tri
met
hyla
nilin
eH
Clz
25-
Xyl
idin
eH
Clz
Test
isM
ouse
4D
ieth
ylst
ilbe
stro
lz Fi
nast
erid
eR
eser
pine
z Ta
mox
ifen
citr
atez
Rat
185-
Aza
cytid
inez
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 1
3-B
utad
iene
z N
-But
yl-N
-(4-
hydr
oxyb
utyl
) nitr
osam
ine
Cad
miu
mch
lori
de
2-C
hlor
o-1
11-
tri
uoro
etha
ne1
1-D
ichl
oro-
1-u
oroe
than
eH
ydro
chlo
rou
oroc
arbo
n12
3M
ethy
lter
t-bu
tyle
ther
z M
ethy
lclo
fena
pate
z M
etro
nida
zole
z N
-Nit
roso
dim
ethy
lam
inez
Oxo
linic
acid
y SD
Z20
0-11
01
11
2-Te
tra
uoro
etha
ney
Tri
chlo
roet
hyle
nez
Tri
nitr
ogly
ceri
nV
inyl
chlo
ride
z
Thy
roid
glan
dH
amst
er4
Hex
achl
orob
enze
nez
Hyd
razi
nez
Met
hylt
hiou
raci
lU
reth
anez
Mou
se18
3-A
min
o-4-
etho
xyac
etan
ilide
y H
Cbl
ueno
1z
tert
-But
ylal
coho
lz C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
24
-Dia
min
oani
sole
sulf
atez
Die
thyl
stil
best
rolz
Dox
ylam
ine
succ
inat
ez E
thio
nam
idey
Eth
ylen
eth
iour
eaz
44
-Met
hyle
nedi
anil
ine
2HC
lz 1
5-N
apht
hale
nedi
amin
ez N
itrob
enze
nez
Oxa
zepa
my
44
-Oxy
dian
iline
z C
Ip
igm
entr
ed3z
Sulf
amet
hazi
ne2
37
8-T
etra
chlo
rodi
benz
o-p-
diox
inz
44
-Thi
odia
nilin
ez
Rat
33A
cryl
amid
e3-
Am
inot
riaz
olez
o-A
nisi
dine
HC
lz B
emit
radi
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bro
mat
epo
tass
ium
z C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
Chl
orop
rene
z 2
4-D
iam
inoa
niso
lesu
lfat
ez N
N-D
ieth
ylth
iour
eay
1-E
thyl
-1-n
itro
sour
ea
Eth
ylen
eth
iour
eaz
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Flu
vast
atin
Gly
cido
lz Io
dina
ted
glyc
erol
z Is
obut
eney
Mal
onal
dehy
des
odiu
msa
ltz
Met
him
azol
e4
4-M
ethy
lene
bis(
NN
-dim
ethy
l)be
nzen
amin
ez 4
4-M
ethy
lene
dian
iline
2H
Clz
Mir
exp
hoto
-N
itro
benz
enez
N-N
itro
sobi
s(2-
oxop
ropy
l)am
ine
44
-Oxy
dian
iline
z Pr
opyl
thio
urac
ilz p-
Ros
anil
ine
HC
lz 2
37
8-Te
trac
hlor
odib
enzo
-p-d
ioxi
nz 4
4-T
hiod
iani
linez
Thi
oura
cilz
Tri
met
hylt
hiou
reay
Vin
ylac
etat
ez Z
inc
dim
ethy
ldith
ioca
rbam
atez
Uri
nary
blad
der
Dog
23
3-D
ichl
orob
enzi
dine
44
-Met
hyle
ne-b
is( 2
-chl
oroa
nilin
e)H
amst
er3
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-t
hiaz
olyl
] hyd
razi
dez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
acet
amid
eN
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] for
mam
idez
Mou
se12
2-A
cety
lam
ino
uore
nez
4-A
min
odip
heny
l2-
Am
inod
iphe
nyle
neox
ide
o-A
nisi
dine
HC
lz 4-
Chl
oro-
4-a
min
odip
heny
leth
erz
p-C
resi
dine
z 4-
Eth
ylsu
lpho
nyln
apht
hale
ne-1
-sul
fona
mid
eN
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez P
hena
cetin
z Te
lone
IIt
echn
ical
grad
ez U
raci
lz
Mon
key
12-
Nap
hthy
lam
inez
Rat
49A
ceta
min
ophe
nz A
llyli
soth
iocy
anat
ey 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 2-
Am
ino-
4-( 5
-nitr
o-2-
fury
l)th
iazo
lez
4-A
min
o-2-
nitr
ophe
noly
11-A
min
ound
ecan
oic
acid
y o-
Ani
sidi
neH
Clz
Ari
stol
ochi
cac
ids
odiu
msa
lt( 7
7A
AI
21
AA
II)
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez C
Id
ispe
rse
blue
1y N
-But
yl-N
-(4-
hydr
oxyb
utyl
) nitr
osam
ine
4-C
hlor
o-o-
phen
ylen
edia
min
ez m
-Cre
sidi
ney
p-C
resi
dine
z C
yclo
phos
pham
idez
Die
thyl
ene
glyc
olD
imet
hyla
rsin
icac
idy
Fose
tylA
lIQ
HC
lM
eA-a
-Cac
etat
ez M
elam
iney
2-M
etho
xy-3
-am
inod
iben
zofu
ran
2-N
apht
hyla
min
ez N
itril
otri
acet
icac
idz
Nitr
ilot
riac
etic
acid
tri
sodi
umsa
ltm
onoh
ydra
tey
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez o-
Nitr
oani
sole
z N
-Nitr
oso-
N-m
ethy
l-N
-dod
ecyl
amin
eN
-Nitr
oso-
N-m
ethy
l-N
-tet
rade
cyla
min
eN
-Nit
roso
-N-m
ethy
ldec
ylam
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
Nitr
osod
ibut
ylam
inez
N-N
itro
sodi
phen
ylam
iney
o-N
itros
otol
uene
N-O
xydi
ethy
lene
thio
carb
amyl
-N-o
xydi
ethy
lene
sulf
enam
ide
Phe
nace
tinz
Phen
azon
eo-
Phen
ylph
enat
eso
dium
y o-
Phen
ylph
enol
y P
otas
sium
bica
rbon
ate
Purp
urin
Que
rcet
iny
p-Q
uino
nedi
oxim
ey Sa
ccha
rin
sodi
umy
Sali
cyla
zosu
lfap
yrid
inez
o-To
luen
esul
fona
mid
eo-
Tolu
idin
eH
Clz
Trp
-P-2
acet
atez
Ura
cilz
Ute
rus
Ham
ster
1N
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aM
ouse
12B
rom
oeth
anez
Chl
oroe
than
ey D
acar
bazi
nez
12-
Dic
hlor
oeth
anez
Die
thyl
stil
best
rolz
Eth
ylen
eox
idez
Gly
cido
lz ( N
-6) -
( Met
hyln
itros
o)ad
enos
ine
Proc
arba
zine
HC
lz 1
23-
Tri
chlo
ropr
opan
ez T
rim
ethy
lpho
spha
tey
Vin
ylac
etat
ez
Rat
26A
cryl
amid
e1-
Ally
l-1-
nitr
osou
rea
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
1-A
myl
-1-n
itros
oure
aA
traz
iney
CI
dir
ectb
lue
15B
rom
ocri
ptin
em
esyl
atey
N-n
-But
yl-N
-nit
roso
urea
Cal
cium
valp
roat
eC
apta
nz 2-
Chl
oro-
11
1-tr
iuo
roet
hane
Dac
arba
zine
z D
amin
ozid
ez 3
3-D
imet
hoxy
benz
idin
e-4
4-d
iisoc
yana
tey
33
-Dim
etho
xybe
nzid
ine
2HC
lD
imet
hyla
min
oeth
ylni
tros
oeth
ylur
ean
itri
tesa
lt1-
Eth
ylni
tros
o-3-
( 2-h
ydro
xyet
hyl)
-ure
a1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
N-H
exyl
nitr
osou
rea
ICR
F-1
59z
Isop
hosp
ham
idez
15-
Nap
htha
lene
diam
inez
Nit
robe
nzen
ez N
orle
stri
nz 4
4-T
hiod
iani
linez
Vin
ylac
etat
ez
Vag
ina
Mou
se1
AZ
Tz
Rat
2A
ZT
z N
-n-B
utyl
-N-n
itro
sour
ea( C
ontin
ued
onne
xtpa
ge)
647
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Vas
cula
rsy
stem
Ham
ster
91
2-D
imet
hylh
ydra
zine
2H
Cl
Gly
cido
lz H
exac
hlor
oben
zene
z N
-Nit
roso
-eth
yl-2
-oxo
prop
ylur
eaN
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aN
-Nitr
oso-
oxop
ropy
lchl
oroe
thyl
urea
N-N
itro
so-o
xopr
opyl
urea
N-N
itros
o-2-
phen
ylet
hylu
rea
Vin
ylch
lori
dez
Mou
se59
A-a
-CN
-Ace
tyl-
4-( h
ydro
xym
ethy
l)ph
enyl
hydr
azin
e1-
Ace
tyl-
2-ph
enyl
hydr
azin
eA
llyl
hydr
azin
eH
Cl
Are
colin
eH
Cl
Aza
thio
prin
eB
enzi
dine
2H
Cl
2-B
iphe
nyla
min
eH
Cly
13-
But
adie
nez
Cap
tafo
lz C
arba
myl
hydr
azin
eH
Cl
4-C
hlor
o-4
-am
inod
iphe
nyle
ther
z 1-
Chl
oro-
4-ni
trob
enze
ney
5-C
hlor
o-o-
tolu
idin
ey 4-
Chl
oro-
o-to
luid
ine
HC
ly p-
Chl
oroa
nilin
eH
Clz
Chl
orop
rene
z C
upfe
rron
z D
acar
bazi
nez
Dam
inoz
idez
24-
Dia
min
otol
uene
2H
Clz
12-
Dib
rom
oeth
anez
Dif
talo
ne7
12-
Dim
ethy
lben
z(a)
anth
race
ne1
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
N-E
thyl
-N-f
orm
ylhy
draz
ine
Eth
ylhy
draz
ine
HC
lG
lu-P
-1z
Glu
-P-2
z p-
Hyd
razi
nobe
nzoi
cac
idH
Cl
1-H
ydro
xysa
frol
ez Is
opre
neM
eA-a
-Cac
etat
ez N
-Met
hyl-
N-f
orm
ylhy
draz
ine
2-M
ethy
l-1-
nitr
oant
hraq
uino
nez
Mic
hler
rsquoske
tone
z 5-
Nitr
o-o-
tolu
idin
ey N
itro
fenz
N-N
itros
o-N
-met
hylu
reaz
Pent
achl
oroa
niso
lez
23
45
6-Pe
ntac
hlor
ophe
nol(
Dow
icid
eE
C-7
)y2
34
56
-Pen
tach
loro
phen
olt
echn
ical
grad
ez n-
Pen
tylh
ydra
zine
HC
lPh
enyl
ethy
lhyd
razi
nesu
lfat
ePh
enyl
hydr
azin
eH
Cl
Ster
igm
atoc
ysti
nz Te
tra
uoro
ethy
lene
z To
luen
edi
isoc
yana
tec
omm
erci
algr
ade
( 24
( 80
) -an
d2
6( 2
0) -
)zo
-Tol
uidi
neH
Clz
24
6-T
rich
loro
anil
iney
24
5-T
rim
ethy
lani
line
HC
lz 2
46-
Tri
met
hyla
nili
neH
Clz
Ure
than
ez V
inyl
carb
amat
eV
inyl
chlo
ride
z V
inyl
uor
idez
Vin
ylid
ene
chlo
ride
y 2
5-X
ylid
ine
HC
lz
Mon
key
2A
ato
xin
B1y
Ure
than
ez
Rat
32A
nilin
eH
Cly
Azo
benz
eney
Ben
zene
z C
livor
ine
Cup
ferr
onz
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
Z-E
thyl
-ON
N-a
zoxy
etha
neZ
-Eth
yl-O
NN
-azo
xym
etha
neI
QH
Cl
Las
ioca
rpin
e4
4-M
ethy
lene
-bis
( 2-c
hlor
oani
line)
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
N-N
itros
o-( 2
-hyd
roxy
prop
yl) -
( 2-h
ydro
xyet
hyl)
amin
eN
itro
so-1
23
6-t
etra
hydr
opyr
idin
eN
-Nitr
osob
is( 2
-oxo
prop
yl) a
min
eN
-Nit
roso
diet
hano
lam
ine
N-N
itro
sodi
ethy
lam
ine
N-N
itros
odim
ethy
lam
inez
N-N
itros
omet
hyl-
( 2-t
osyl
oxye
thyl
) am
ine
N-N
itros
omor
phol
ine
N-N
itro
sopy
rrol
idin
ez Pe
tasi
teni
neS
teri
gmat
ocys
tinz
Sym
phyt
ine
Tetr
auo
roet
hyle
nez
o-To
luid
ine
HC
lz T
rp-P
-2ac
etat
ez V
inyl
brom
ide
Vin
ylch
lori
dez
Vin
yl
uori
dez
aT
here
was
nore
port
edta
rget
site
in1
spec
ies
( rat
sor
mic
e)fo
r5
chem
ical
sw
ithsu
pers
crip
tsb
utth
ech
emic
alw
asev
alua
ted
byth
epu
blis
hed
auth
oras
aca
rcin
ogen
ald
rinz
diel
drin
z N
-nit
roso
pyrr
olid
inez
23
45
6-pe
ntac
hlor
ophe
nol
( Dow
icid
eE
C-7
)ya
ndur
etha
nez
bN
asal
cavi
tyin
clud
estis
sues
ofth
eno
sen
asal
turb
inat
esp
aran
asal
sinu
ses
and
trac
hea
c Ora
lcav
ityin
clud
estis
sues
ofth
em
outh
oro
phar
ynx
phar
ynx
and
lary
nx
Ach
emic
alis
liste
dun
der
each
orga
nev
alua
ted
aspo
sitiv
ein
anex
peri
men
tin
that
spec
ies
byat
leas
t1au
thor
The
refo
rea
chem
ical
may
beli
sted
unde
rse
vera
ltar
geto
rgan
san
dev
ery
chem
ical
liste
din
the
tabl
eis
posi
tive
inat
leas
t1sp
ecie
sIn
orde
rto
com
pare
resu
ltsin
rats
and
mic
esy
mbo
lsfo
llow
chem
ical
ste
sted
inbo
thsp
ecie
sa
zin
dica
tes
that
the
chem
ical
ispo
sitiv
eat
som
esi
tein
both
spec
ies
and
ay
indi
cate
sth
atit
was
test
edin
both
butp
ositi
vein
only
1a
Nth
enu
mbe
rof
chem
ical
sw
ithat
leas
t1po
sitiv
ete
stat
that
site
inth
atsp
ecie
sB
ecau
sem
any
chem
ical
sin
duce
tum
ors
atm
ore
than
1si
tein
agi
ven
spec
ies
man
ych
emic
als
appe
arm
ore
than
once
inth
eta
ble
648
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649
species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters
RESULTS IN RATS AND MICE
For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens
TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database
Chemicals evaluated as carcinogenic in
Rats Mice
All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)
Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2
a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not
b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats
All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical
to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included
The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site
Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common
650 GOLD ET AL TOXICOLOGIC PATHOLOGY
TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)
Target site Agent mixture or industrial process
Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e
Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke
Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products
Brain Vinyl chloride a
Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e
Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena
Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system
Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as
a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell
lymphotropic virus type I (HTLV-I) Vinyl chloridea
Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production
Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)
Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea
Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea
Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)
Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea
Mesenchymal tumors Azathioprinea
Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust
Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust
Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid
(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke
Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production
8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots
Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e
Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays
IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD
IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no
tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance
is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651
sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites
Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to
be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)
Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)
Target Organs of Human CarcinogensTo complement the compendium of target organs in car-
cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke
In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)
Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens
Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from
bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)
ACKNOWLEDGMENTS
We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention
REFERENCES
1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56
2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600
3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998
4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685
5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404
6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605
7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246
8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100
9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash
23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC
11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the
652 GOLD ET AL TOXICOLOGIC PATHOLOGY
US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240
12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute
13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program
14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX
15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11
16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash
34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c
Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729
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Tri
met
hyla
nili
nez
24
5-T
rim
ethy
lani
line
HC
lz 2
46-
Tri
met
hyla
nilin
eH
Clz
24
6-T
rini
tro-
13-
dim
ethy
l-5-
tert
-but
ylbe
nzen
eT
ris(
2-ch
loro
ethy
l)ph
osph
atez
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez T
ris(
2-et
hylh
exyl
) pho
spha
tey
Trp
-P-1
acet
atez
Trp
-P-2
acet
atez
Ure
than
ez V
inyl
carb
amat
eV
inyl
uo
ride
z 2
5-X
ylid
ine
HC
lz C
Id
ispe
rse
yell
ow3z
Zea
rale
none
y
Mon
key
8A
ato
xin
B1y
Cyc
asin
and
met
hyla
zoxy
met
hano
lace
tate
IQ
z N
-Nitr
osod
ieth
ylam
ine
N-N
itro
sodi
prop
ylam
ine
N-N
itro
sopi
peri
dine
z S
teri
gmat
ocys
tinz
Ure
than
ez
Rat
206
Ace
tam
idez
Ace
tam
inop
henz
Ace
toxi
me
2-A
cety
lam
ino
uore
nez
A
atox
icol
A
atox
inB
y 1A
at
oxin
cru
dez
1-A
min
o-2
4-di
brom
oant
hraq
uino
nez
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
1-A
min
o-2-
met
hyla
nthr
aqui
none
z 2-
Am
inoa
nthr
aqui
none
z o-
Am
inoa
zoto
luen
ey 11
-Am
inou
ndec
anoi
cac
idy
Ara
mit
ez A
rocl
or12
60A
uram
ine-
Oz
Azo
xym
etha
neB
emit
radi
ne
Ben
zidi
ne3
-Ben
zyls
ydno
ne-4
-ace
tam
idez
Bis
( 23
-dib
rom
opro
pyl)
phos
phat
em
agne
sium
salt
CI
dir
ectb
lue
15
Bro
mod
ichl
orom
etha
nez
Bud
eson
ide
Cap
tafo
lz C
arbo
nte
trac
hlor
idez
Chl
oren
dic
acid
z C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
4-C
hlor
o-4
-am
inod
iphe
nyle
ther
z 2-
Chl
oro-
5-( 3
5-d
imet
hylp
iper
idin
osul
phon
yl) b
enzo
icac
id[
4-C
hlor
o-6-
( 23
-xy
lidi
no) -
2-py
rim
idin
ylth
io] a
ceti
cac
idz
4-C
hlor
o-6-
( 23
-xyl
idin
o)-2
-pyr
imid
inyl
thio
( N-b
-hyd
roxy
ethy
l)ac
etam
idez
Chl
orob
enze
ney
Chl
orof
orm
z 3-
( p-C
hlor
ophe
nyl)
-11
-dim
ethy
lure
ay C
ipro
bra
tez
Cliv
orin
eC
lob
rate
y C
loph
enA
30C
oum
arin
z p-
Cre
sidi
nez
Cro
tona
ldeh
yde
Cup
ferr
onz
Cyc
lope
ntan
one
oxim
eD
DT
z D
ecab
rom
odip
heny
loxi
dey
Deh
ydro
epia
ndro
ster
one
Deh
ydro
epia
ndro
ster
one
acet
ate
24-
Dia
min
otol
uene
z 2
4-D
iam
inot
olue
ne2
HC
lz 1
2-D
ibro
moe
than
ez D
ichl
oroa
ceti
cac
idz
Dic
hlor
oace
tyle
nez
NN
-Die
thyl
-4-(
4-[
pyri
dyl-
1-o
xide
] azo
) ani
line
Die
thyl
stil
best
rolz
Dim
etho
xane
3
3-D
imet
hoxy
benz
idin
e2H
Cl
56-
Dim
etho
xyst
erig
mat
ocys
tinN
N-D
imet
hyl-
4-am
inoa
zobe
nzen
e6-
Dim
ethy
lam
ino-
44-
diph
enyl
-3-h
epta
nola
ceta
teH
Cly
33
-Dim
ethy
lben
zidi
ne2
HC
lz D
imet
hyln
itram
ine
Din
itros
ohom
opip
eraz
ine
26-
Din
itro
tolu
ene
24-
Din
itrot
olue
ne( c
onta
inin
g1
0-1
52
6-di
nitr
otol
uene
)z
Din
itrot
olue
net
echn
ical
grad
e( 2
4( 7
7) -
and
26
( 19
) -)
14-
Dio
xane
z D
ipen
tyln
itro
sam
ine
Dox
ylam
ine
succ
inat
ez E
thin
yles
trad
iol
Eth
ioni
ne
dl-E
thio
nine
z 4-
Eth
oxy-
phen
ylur
eaE
thyl
alco
holy
Z-E
thyl
-ON
N-a
zoxy
etha
neZ
-Eth
yl-O
NN
-azo
xym
etha
neE
thyl
ene
thio
urea
z di
( 2-E
thyl
hexy
l)ph
thal
atez
Flu
cona
zole
y N
-(2-
Flu
oren
yl) -
22
2-tr
iuo
roac
etam
ide
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-t
hiaz
olyl
] hyd
razi
dez
Fum
onis
inB
1F
uran
z Fu
rfur
alz
Glu
-P-1
z G
lu-P
-2z
FDamp
Cgr
een
no1
y H
CD
Dm
ixtu
rez
Hex
achl
orob
enze
nez
a-1
23
45
6-H
exac
hlor
ocyc
lohe
xane
z H
ydra
zine
z H
ydra
zine
sulf
atez
Hyd
razo
benz
enez
Hyd
roch
loro
uor
ocar
bon
123
N-H
ydro
xy-2
-ace
tyla
min
ouo
rene
z 1-
Hyd
roxy
anth
raqu
inon
e1-
( 2-H
ydro
xyet
hyl)
-nitr
oso-
3-ch
loro
ethy
lure
a1
-Hyd
roxy
safr
olez
IQz
IQH
Cl
Ison
iazi
dz K
epon
ez L
asio
carp
ine
MeA
-a-C
acet
atez
MeI
Qxz
Met
hapy
rile
neH
Cl
Z-M
ethy
l-O
NN
-azo
xyet
hane
Met
hylc
arba
mat
ey M
ethy
lclo
fena
pate
z 3
-Met
hyl-
4-di
met
hyla
min
oazo
benz
ene
2-M
ethy
l-1-
nitr
oant
hraq
uino
nez
4-( 4
-N-M
ethy
l-N
-nit
rosa
min
osty
ryl)
quin
olin
e4
4-M
ethy
lene
-bis
( 2-c
hlor
oani
line
) 4
4-M
ethy
lene
-bis
( 2-m
ethy
lani
line
) 4
4-M
ethy
lene
dian
ilin
e2H
Clz
4-( M
ethy
lnit
rosa
min
o)-1
-(3-
pyri
dyl)
-1-(
buta
none
) M
etro
nida
zole
z M
ichl
errsquos
keto
nez
Mir
exz
Mon
ocro
tali
neN
afen
opin
Nit
rite
sod
ium
y N
itrob
enze
nez
2-N
itro
buta
ne2
-Nit
ro
uore
ne3
-Nit
rope
ntan
eN
-Nitr
oso-
bis-
( 44
4-t
ri
uoro
-N-b
utyl
) am
ine
1-N
itros
o-5
6-di
hydr
oura
cil
N-N
itro
so-2
3-d
ihyd
roxy
prop
ylet
hano
lam
ine
1-N
itros
o-1-
hydr
oxye
thyl
-3-c
hlor
oeth
ylur
ea1
-Nitr
oso-
1-( 2
-hyd
roxy
prop
yl) -
3-ch
loro
ethy
lure
aN
-Nitr
oso-
( 2-h
ydro
xypr
opyl
) -( 2
-hyd
roxy
ethy
l)am
ine
N-N
itros
o-N
-met
hyl-
N-d
odec
ylam
ine
Nit
roso
-N-m
ethy
l-N
-(2-
phen
yl) e
thyl
amin
e
( Con
tinue
don
next
page
)
643
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
N-N
itro
so-N
-met
hyld
ecyl
amin
e3-
Nit
roso
-2-o
xazo
lidin
one
Nit
roso
-2-o
xopr
opyl
etha
nola
min
eN
itro
so-1
23
6-t
etra
hydr
opyr
idin
eN
-Nit
roso
ally
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itro
soal
lyl-
2-ox
opro
pyla
min
eN
-Nitr
osoa
llyl
etha
nola
min
eN
-Nit
roso
bis(
2-ox
opro
pyl)
amin
eN
itro
sodi
buty
lam
inez
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
diet
hyla
min
eN
-Nitr
osod
imet
hyla
min
ez p-
Nitr
osod
iphe
nyla
min
ez N
-Nit
roso
dipr
opyl
amin
eN
itros
odod
ecam
ethy
lene
imin
eN
-Nit
roso
ephe
drin
eN
itro
soet
hylm
ethy
lam
ine
Nitr
osoh
epta
met
hyle
neim
ine
N-N
itros
omet
hyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nit
roso
met
hyl-
( 2-h
ydro
xyet
hyl)
amin
eN
-Nitr
osom
ethy
l-( 3
-hyd
roxy
prop
yl) a
min
eN
-Nitr
osom
ethy
l(2-
oxop
ropy
l)am
ine
N-N
itro
som
ethy
l-( 2
-tos
ylox
yeth
yl) a
min
eN
itro
som
ethy
lund
ecyl
amin
eN
-Nit
roso
mor
phol
ine
N-N
itros
opip
erid
inez
N-N
itro
sopy
rrol
idin
ez N
-Nit
roso
thia
ldin
eo-
Nit
roso
tolu
ene
Nor
lest
rinz
N-(
9-O
xo-2
-uo
reny
l)ac
etam
ide
44
-Oxy
dian
iline
z 2
34
56-
Pent
achl
orop
heno
lte
chni
calg
rade
z P
etas
iten
ine
Phe
noba
rbit
als
odiu
mz
1-P
heny
lazo
-2-n
apht
holy
o-P
heny
lene
diam
ine
2HC
lz P
iper
onyl
buto
xide
z P
olyb
rom
inat
edbi
phen
ylm
ixtu
rez
Pre
dnis
olon
eP
yril
amin
em
alea
tey
CI
aci
dre
d11
4C
Ip
igm
entr
ed3z
Damp
Cre
dno
5z
Damp
Cre
dno
9y
FD
ampC
red
no1
p-
Ros
anili
neH
Clz
Saf
role
z Se
leni
umsu
lde
z Se
nkir
kine
Ste
rigm
atoc
ystin
z S
ymph
ytin
eTa
mox
ifen
citr
atez
Telo
neII
tec
hnic
algr
adez
33
44
-Te
traa
min
obip
heny
l4H
Clz
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tetr
auo
roet
hyle
nez
Thi
oace
tam
idez
44
-Thi
odia
nilin
ez To
luen
edi
isoc
yana
te
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
Tri
amci
nolo
neac
eton
ide
24
5-T
rim
ethy
lani
line
z 2
45-
Tri
met
hyla
nili
neH
Clz
24
6-T
rim
ethy
lani
line
HC
lz T
rini
trog
lyce
rin
Trp
-P-1
acet
atez
Trp
-P-2
acet
atez
Vin
ylac
etat
ez V
inyl
brom
ide
Vin
ylch
lori
dez
Vin
yl
uori
dez
CI
dis
pers
eye
llow
3z
Tre
esh
rew
1A
ato
xin
B1y
Lun
gH
amst
er3
Met
hyln
itro
sam
ino-
NN
-dim
ethy
leth
ylam
ine
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
1-N
itro
so-3
45
-tri
met
hylp
iper
azin
eM
ouse
116
Ace
tald
ehyd
em
ethy
lfor
myl
hydr
azon
eN
-Ace
tyl-
4-( h
ydro
xym
ethy
l)ph
enyl
hydr
azin
e1-
Ace
tyl-
2-is
onic
otin
oylh
ydra
zine
A
llyl
hydr
azin
eH
Cl
1-A
min
o-2
4-di
brom
oant
hraq
uino
nez
Are
coli
neH
Cl
5-A
zacy
tidi
nez
Ben
zene
z B
enzo
fura
nz B
enzo
tric
hlor
ide
Ben
zoyl
hydr
azin
eB
enzy
lhyd
razi
ne2
HC
l2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bis
( 2-c
hlor
o-1-
met
hyle
thyl
) eth
er
tech
nica
lgra
dey
Bis
-(ch
loro
met
hyl)
ethe
rz 1
3-B
utad
iene
z N
-n-B
utyl
-N-f
orm
ylhy
draz
ine
But
ylat
edhy
drox
ytol
uene
y 1
1-di
-n-B
utyl
hydr
azin
en-
But
ylhy
draz
ine
HC
l1
2-di
-N-B
utyl
hydr
azin
e2H
Cl
Caf
feic
acid
z C
arba
myl
hydr
azin
eH
Cl
1-C
arba
myl
-2-p
heny
lhyd
razi
neC
hlor
ambu
cilz
Chl
orop
rene
z C
obal
tsul
fate
hept
ahyd
rate
z C
oum
arin
z C
yclo
phos
pham
idez
Dac
arba
zine
z D
amin
ozid
ez p
p-D
DD
y D
DT
z 1
1-D
iall
ylhy
draz
ine
12-
Dia
llyl
hydr
azin
e2H
Cl
Dib
enz(
ah)
anth
race
ne1
2-D
ibro
mo-
3-ch
loro
prop
anez
Dib
rom
odul
cito
lz 1
2-D
ibro
moe
than
ez D
ibro
mom
anni
tolz
12-
Dic
hlor
oeth
anez
12-
Dif
orm
ylhy
draz
ine
Dih
ydro
safr
olez
25-
Dim
etho
xy-4
-am
inos
tilbe
nez
33
-Dim
ethy
lben
zidi
ne2
HC
lz 1
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
a-E
cdys
one
Est
radi
olm
usta
rdy
N-E
thyl
-N-f
orm
ylhy
draz
ine
Eth
ylen
eim
ine
Eth
ylen
eox
idez
Eth
ylhy
draz
ine
HC
l5-
Flu
orou
raci
ly Fo
rmyl
hydr
azin
eG
lyci
dolz
c-1
23
45
6-H
exac
hlor
ocyc
lohe
xane
y H
exan
alm
ethy
lfor
myl
hydr
azon
eH
ydra
zine
z H
ydra
zine
sulf
atez
IQz
Isob
utyl
nitr
itez
Ison
iazi
dz Is
onic
otin
icac
idva
nilly
liden
ehyd
razi
de
Isop
rene
Lov
asta
tinM
eIQ
xz M
elph
alan
z 1-
Met
hyl-
14-
dihy
dro-
7-[ 2
-(5-
nitr
ofur
yl) v
inyl
] -4-
oxo-
18-
naph
thyr
idin
e-3-
carb
oxyl
ate
pota
ssiu
m
N-M
ethy
l-N
-for
myl
hydr
azin
eM
ethy
lmet
hane
sulf
onat
e3-
Met
hylb
utan
alm
ethy
lfor
myl
hydr
azon
eM
ethy
lene
chlo
ride
z M
ethy
lhyd
razi
ne
Met
hylh
ydra
zine
sulf
ate
( N-6
) -( M
ethy
lnit
roso
) ade
nine
(N
-6) -
( Met
hyln
itro
so) a
deno
sine
N-M
ethy
lola
cryl
amid
ey M
etro
nida
zole
z M
olyb
denu
mtr
ioxi
dey
Mon
oace
tylh
ydra
zine
Nap
htha
lene
15
-Nap
htha
lene
diam
inez
Nic
otin
icac
idhy
draz
ide
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez 3-
Nitr
o-3-
hexe
nez
Nit
robe
nzen
ez N
itrom
etha
nez
Nit
roso
dibu
tyla
min
ez N
-Nit
roso
dim
ethy
lam
inez
N-N
itros
ohex
amet
hyle
neim
ine
N-N
itro
sopi
peri
dine
z O
zone
y Pe
ntan
alm
ethy
lfor
myl
hydr
azon
en-
Pen
tylh
ydra
zine
HC
lPh
enes
teri
nz Ph
enyl
ethy
lhyd
razi
nesu
lfat
eP
roca
rbaz
ine
HC
lz N
-N-P
ropy
l-N
-for
myl
hydr
azin
eP
ropy
lhyd
razi
neH
Cl
Sel
eniu
msu
lde
z S
trep
tozo
toci
nz Su
lfal
late
z Te
lone
IIt
echn
ical
grad
ez 3
34
4-T
etra
amin
obip
heny
l4H
Clz
Tetr
anitr
omet
hane
z T-
2to
xin
Tri
chlo
roet
hyle
nez
Tri
ura
lint
echn
ical
grad
ey 2
45-
Tri
met
hyla
nilin
eH
Clz
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez U
reth
anez
Vin
ylch
lori
dez
Vin
ylu
orid
ez V
inyl
iden
ech
lori
dey
24-
Xyl
idin
eH
Cly
Mon
key
1U
reth
anez
Rat
551-
Ally
l-1-
nitr
osou
rea
2-A
min
o-5-
( 5-n
itro
-2-f
uryl
) -1
34-
oxad
iazo
le2
-Am
ino-
5-( 5
-nitr
o-2-
fury
l)-1
34
-thi
adia
zole
2-A
min
o-5-
nitr
othi
azol
ey 1-
Am
yl-1
-nitr
osou
rea
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
is-(
chlo
rom
ethy
l)et
herz
HC
blue
no1
z B
rom
oeth
anez
N-n
-But
yl-N
-nit
roso
urea
Cad
miu
mch
lori
deC
adm
ium
sulp
hate
( 11
) 1-
Chl
oroe
thyl
nitr
oso-
3-( 2
-hyd
roxy
prop
yl) u
rea
Chl
orop
rene
z C
obal
tsul
fate
hept
ahyd
rate
z 1
2-D
ibro
moe
than
ez D
imet
hylh
ydro
gen
phos
phit
ey tr
ans-
2-[(
Dim
ethy
lam
ino)
met
hylim
ino]
-5-
[ 2-(
5-ni
tro-
2-fu
ryl)
viny
l] -1
34-
oxad
iazo
le3
3-D
imet
hylb
enzi
dine
2H
Clz
12-
Epo
xybu
tane
y 1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
N-H
exyl
nitr
osou
rea
Hyd
razi
nez
Hyd
razi
nesu
lfat
ez 1-
( 2-H
ydro
xyet
hyl)
-1-n
itro
sour
eaz
Isob
utyl
nitr
itez
Ison
iazi
dz 4
4-M
ethy
lene
-bi
s(2-
chlo
roan
iline
) 4-
( Met
hyln
itros
amin
o)-1
-(3-
pyri
dyl)
-1-b
utan
ol4
-(M
ethy
lnit
rosa
min
o)-1
-(3-
pyri
dyl)
-1-(
buta
none
) N
-[ 3
-(5-
Nitr
o-2-
fury
l)-
12
4-ox
adia
zole
-5-y
l] -m
ethy
lace
tam
ide
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
3-N
itro-
3-he
xene
z 5-
Nitr
oace
naph
then
ez N
-Nit
roso
-bis
-(4
44-
tri
uoro
-N-b
utyl
) am
ine
N-N
itros
o-N
-met
hyl-
N-d
odec
ylam
ine
N-N
itros
o-N
-met
hyl-
N-t
etra
decy
lam
ine
N-N
itro
so-N
-met
hyld
ecyl
amin
eN
-Nitr
oso-
N-m
ethy
lure
az N
-Nitr
osob
is( 2
-hyd
roxy
prop
yl)
amin
eN
-Nitr
osob
is-2
3-d
ihyd
roxy
prop
ylam
ine
( 2-o
xopr
opyl
) am
ine
Nitr
osod
ibut
ylam
inez
N-N
itros
odim
ethy
lam
inez
N-N
itro
soep
hedr
ine
Nitr
osoe
thyl
met
hyla
min
eN
-Nit
roso
met
hyl
N-N
itro
som
ethy
l-( 3
-hyd
roxy
prop
yl) a
min
eN
itro
som
ethy
lund
ecyl
amin
eC
Ia
cid
red
114
Sod
ium
dich
rom
ate
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tetr
anit
rom
etha
nez
24
5-T
rim
ethy
lani
line
z 2
46-
Tri
met
hyla
nili
neH
Clz
Vin
ylch
lori
dez
Mam
mar
ygl
and
Dog
1Ly
nest
reno
lH
amst
er1
Vin
ylch
lori
dez
Mou
se24
5-A
zacy
tidin
ez B
enze
nez
CI
dir
ectb
lack
381
3-B
utad
iene
z C
alci
fero
lC
hlor
opre
nez
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
Die
thyl
stilb
estr
olz
a-E
cdys
one
Est
radi
olE
thyl
ene
oxid
ez F
uros
emid
ey G
lyci
dolz
Gri
seof
ulvi
nIs
onia
zidz
Ison
icot
inic
acid
vani
llylid
eneh
ydra
zide
( N
-6) -
( Met
hyln
itros
o)ad
enos
ine
Nitr
oben
zene
z R
eser
pine
z Su
lfal
late
z V
inyl
chlo
ride
z V
inyl
uor
idez
Vin
ylid
ene
chlo
ride
y
644
Rat
102
4-A
cety
lam
inob
iphe
nyl
2-A
cety
lam
ino
uore
nez
Acr
onyc
ine
Acr
ylam
ide
Acr
ylon
itri
leA
F-2
z 1-
Ally
l-1-
nitr
osou
rea
2-A
min
o-5-
( 5-n
itro-
2-fu
ryl)
-13
4-
oxad
iazo
le2
-Am
ino-
5-( 5
-nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
e2-
Am
ino-
5-ni
trot
hiaz
oley
4-A
min
odip
heny
lHC
l1-
Am
yl-1
-nit
roso
urea
Atr
azin
ey B
emit
radi
ne
Ben
zidi
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
4-B
is( 2
-hyd
roxy
ethy
l)am
ino-
2-( 5
-nit
ro-2
-thi
enyl
) qui
nazo
line
13-
But
adie
nez
N-n
-But
yl-N
-nitr
osou
rea
Cap
tafo
lz C
arbo
nte
trac
hlor
idez
Car
boxy
met
hyln
itros
oure
aC
hlor
ambu
cilz
Chl
orop
rene
z C
ytem
bena
y D
acar
bazi
nez
N-1
-Dia
ceta
mid
ouo
rene
46
-Dia
min
o-2-
( 5-n
itro-
2-fu
ryl)
-S-t
riaz
ine
24-
Dia
min
oani
sole
sulf
atez
24-
Dia
min
otol
uene
z 1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dib
rom
oman
nito
lz 1
3-D
ibut
yl-1
-nit
roso
urea
33
-Dic
hlor
oben
zidi
ne1
2-D
ichl
oroe
than
ez 3
3-D
imet
hoxy
benz
idin
e2H
Cl
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
12-
Dim
ethy
l-5-
nitr
oim
idaz
ole
tran
s-2-
[(D
imet
hyla
min
o)m
ethy
limin
o]-5
-[2-
( 5-n
itro
-2-f
uryl
) vin
yl] -
13
4-ox
adia
zole
Dim
ethy
lam
inoe
thyl
nitr
osoe
thyl
urea
nitr
ite
salt
33
-Dim
ethy
lben
zidi
ne2
HC
lz 2-
( 22
-Dim
ethy
lhyd
razi
no) -
4-( 5
-nitr
o-2-
fury
l)th
iazo
le
24-
Din
itro
tolu
ene
( con
tain
ing
10-
15
24-
Dio
xane
z 1-
Eth
ylni
tros
o-3-
( 2-h
ydro
xyet
hyl)
-ure
a1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
6-di
nitr
otol
uene
)zN
-(2-
Fluo
reny
l)-2
22
-tri
uo
roac
etam
ide
Form
icac
id2-
( 4-m
ethy
l-2-
thia
zoly
l)hy
draz
ide
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-
thia
zoly
l] hyd
razi
dez
Gly
cido
lz H
exam
ethy
lmel
amin
eN
-Hex
ylni
tros
oure
a2-
Hyd
razi
no-4
-(p-
amin
ophe
nyl)
thia
zole
z 2-
Hyd
razi
no-4
-( 5
-nit
ro-2
-fur
yl) t
hiaz
olez
2-H
ydra
zino
-4-(
p-ni
trop
heny
l)th
iazo
lez
Hyd
razo
benz
enez
1-( 2
-Hyd
roxy
ethy
l)-3
-[( 5
-nit
rofu
rfur
ylid
ene)
amin
o]-2
-im
idaz
olid
inon
e1-
( 2-H
ydro
xyet
hyl)
-nit
roso
-3-e
thyl
urea
1-(
2-H
ydro
xyet
hyl)
-1-n
itros
oure
az In
dom
etha
cin
IQz
IQH
Cl
Ison
iazi
dz 2-
Met
hoxy
-3-a
min
odib
enzo
fura
n4-
Met
hyl-
1-[(
5-ni
trof
urfu
rylid
ene)
amin
o]-2
-im
idaz
olid
inon
eN
-(N
-Met
hyl-
N-n
itro
soca
rbam
oyl)
-l-o
rnit
hine
3-M
ethy
lcho
lant
hren
e4
4-M
ethy
lene
-bi
s(2-
chlo
roan
iline
) 4
4-M
ethy
lene
-bis
( 2-m
ethy
lani
line)
Met
hyle
nech
lori
dez
Met
roni
dazo
lez
l-5-
Mor
phol
inom
ethy
l-3-
[(5-
nitr
ofur
fury
lide
ne) a
min
o]-
2-ox
azol
idin
one
HC
lN
ithia
zide
z 5-
Nitr
o-2-
fura
ldeh
yde
sem
icar
bazo
nez
3-( 5
-Nitr
o-2-
fury
l)-i
mid
azo(
12-
a)
pyri
dine
z 4-
( 5-N
itro-
2-fu
ryl)
thia
zole
N
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] ace
tam
ide
NN
-[6-
( 5-N
itro
-2-f
uryl
) -S-
tria
zine
-24
-diy
l] bis
acet
amid
e5-
Nitr
oace
naph
then
ez 1-
[(5-
Nit
rofu
rfur
ylid
ene)
amin
o]-2
-im
idaz
olid
inon
eN
itrom
etha
nez
1-N
itrop
yren
eN
orle
stri
nz O
chra
toxi
nA
z N
-(9-
Oxo
-2-
uore
nyl)
acet
amid
ePh
enac
etin
z Ph
enes
teri
nz Ph
IPH
Clz
Proc
arba
zine
HC
lz Pr
opan
esu
lton
e1
2-Pr
opyl
ene
oxid
ez St
yren
ey Su
lfal
late
z 4
4-S
ulfo
nylb
isac
etan
ilid
eTo
luen
edi
isoc
yana
te
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
o-T
olui
dine
HC
lz 1
23-
Tri
chlo
ropr
opan
ez 2
22-
Tri
uor
o-N
-[4-
( 5-n
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] ace
tam
idez
Trp
-P-2
acet
atez
Vin
ylch
lori
dez
FD
ampC
viol
etno
1y
Mes
ovar
ium
Rat
2Sa
lbut
amol
Ter
buta
line
Myo
card
ium
Mou
se2
Est
radi
olm
usta
rdy
Phen
este
rinz
Nas
alca
vity
bB
ush
baby
1N
-Nitr
osod
ieth
ylam
ine
Ham
ster
11A
ceta
ldeh
yde
Dia
llyln
itros
amin
eD
imet
hylc
arba
myl
chlo
ride
Hyd
razi
nez
Met
hyln
itro
sam
ino-
NN
-dim
ethy
leth
ylam
ine
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
N-N
itro
soal
lyl-
2-ox
opro
pyla
min
eN
-Nitr
osom
ethy
l-2
3-di
hydr
oxyp
ropy
lam
ine
N-N
itros
omor
phol
ine
N-N
itros
onor
nico
tine
N-N
itros
opip
erid
inez
Mou
se6
Ally
lgly
cidy
leth
ery
12-
Dib
rom
o-3-
chlo
ropr
opan
ez 1
2-D
ibro
moe
than
ez Fo
rmal
dehy
dez
N-N
itro
sohe
xam
ethy
lene
imin
e1
2-Pr
opyl
ene
oxid
ez
Rat
43A
ceta
ldeh
yde
Acr
ylon
itril
e1-
Azo
xypr
opan
eB
enze
nez
Bis
-(ch
loro
met
hyl)
ethe
rz p-
Cre
sidi
nez
Dia
llyln
itros
amin
e1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dim
ethy
lnitr
amin
eD
imet
hylv
inyl
chlo
ride
z D
initr
osoh
omop
iper
azin
e1
4-D
ioxa
nez
12-
Epo
xybu
tane
y Z
-Eth
yl-O
NN
-azo
xyet
hane
E
thyl
benz
ene
Eth
ylni
tros
ocya
nam
ide
Form
alde
hyde
z H
exam
ethy
lpho
spho
ram
ide
Hyd
razi
nez
N-N
itro
so-N
-met
hyld
ecyl
amin
edi
( N-N
itro
so) -
perh
ydro
pyri
mid
ine
N-N
itros
o(2
22-
tri
uoro
ethy
l)et
hyla
min
e1-
Nitr
oso-
34
5-tr
imet
hylp
iper
azin
eN
-Nitr
osoa
llyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nit
roso
ally
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itro
soal
lyle
than
olam
ine
N-N
itros
obis
( 2-h
ydro
xypr
opyl
) am
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
dipr
opyl
amin
eN
itros
oeth
ylm
ethy
lam
ine
N-N
itros
omet
hyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nitr
osom
ethy
l-( 2
-hyd
roxy
ethy
l)am
ine
N-N
itro
som
ethy
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itros
omet
hyl(
2-ox
opro
pyl)
amin
eN
-Nit
roso
norn
icot
ine-
1-N
-oxi
de
N-N
itro
sopi
peri
dine
z P
hena
cetin
z Ph
enyl
glyc
idyl
ethe
r1
2-Pr
opyl
ene
oxid
ez V
inyl
acet
atez
Vin
ylch
lori
dez
Ner
vous
Mou
se3
13-
But
adie
nez
N-N
itros
odim
ethy
lam
inez
Pro
carb
azin
eH
Clz
syst
emR
at21
Acr
ylam
ide
Acr
ylon
itril
eB
rom
oeth
anez
Chl
oram
buci
lz 1-
( 4-C
hlor
ophe
nyl)
-1-p
heny
l-2-
prop
ynyl
carb
amat
eC
yclo
phos
pham
idez
1-E
thyl
-1-n
itros
oure
aE
thyl
eneo
xide
z 1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
eaG
lu-P
-1z
Glu
-P-2
z G
lyci
dolz
R(
) -2-
Met
hyl-
N-n
itro
sopi
peri
dine
S(
) -2-
Met
hyl-
N-n
itro
sopi
peri
dine
M
ethy
lnit
ram
ine
N-N
itros
o-N
-met
hylu
reaz
N-N
itros
odie
than
olam
ine
1-P
heny
l-3
3-di
met
hyltr
iaze
neP
roca
rbaz
ine
HC
lz P
ropa
nesu
ltone
Vin
ylch
lori
dez
Ora
lcav
ityc
Ham
ster
4A
ceta
ldeh
yde
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
N-N
itros
omor
phol
ine
N-N
itro
sopi
peri
dine
z
Mou
se3
N-N
itros
ohex
amet
hyle
neim
ine
12
3-T
rich
loro
prop
anez
Vin
ylac
etat
ez
Rat
32A
cryl
amid
eA
cryl
onitr
ile
Ben
zene
z 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
CI
dir
ectb
lue
15C
Id
irec
tblu
e21
8z C
hlor
opre
nez
3-D
iazo
tyra
min
eH
Cl
12-
Dib
rom
o-3-
chlo
ropr
opan
ez 3
3-D
imet
hoxy
benz
idin
e2H
Cl
33
-Dim
ethy
lben
zidi
ne2
HC
lz D
imet
hylv
inyl
chlo
ride
z D
initr
osoh
omop
iper
azin
eG
lyci
dolz
IQz
MeA
-a-C
acet
atez
N-N
itros
o-2
3-di
hydr
oxyp
ropy
l-2-
hydr
oxyp
ropy
lam
ine
Nit
roso
-23
-dih
ydro
xypr
opyl
-2-
oxop
ropy
lam
ine
Nitr
oso-
N-m
ethy
l-N
-(2-
phen
yl) e
thyl
amin
eN
itro
soam
ylur
etha
nN
-Nitr
osod
ieth
ylam
ine
Nit
roso
ethy
lure
than
N
itros
ohep
tam
ethy
lene
imin
e1-
Nitr
osoh
ydan
toin
N-N
itros
omet
hyl(
2-ox
opro
pyl)
amin
eN
-Nit
roso
thia
ldin
eN
-Nitr
osot
hiom
orph
olin
eC
Ia
cid
red
114
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tolu
eney
12
3-T
rich
loro
prop
anez
Xyl
ene
mix
ture
( m-x
ylen
eo-
xyle
nep
-xyl
ene)
Ova
ryM
ouse
10B
enze
nez
13-
But
adie
nez
Die
thyl
stil
best
rolz
N-M
ethy
lola
cryl
amid
ey 5-
Nitr
o-2-
fura
ldeh
yde
sem
icar
bazo
nez
5-N
itroa
cena
phth
enez
1-[(
5-N
itro
furf
uryl
iden
e)am
ino]
hyda
ntoi
nz P
heno
lpht
hale
inz
Tam
oxif
enci
trat
ez 4-
Vin
ylcy
cloh
exen
ePa
ncre
asH
amst
er3
Nitr
oso-
23-
dihy
drox
ypro
pyl-
2-ox
opro
pyla
min
eN
itro
so-2
6-d
imet
hylm
orph
olin
eN
itro
so-2
-oxo
prop
ylet
hano
lam
ine
Mon
key
1U
reth
anez
Rat
222-
Am
ino-
5-ni
trop
heno
ly 1-
( Am
inom
ethy
l)cy
cloh
exan
eace
ticac
idA
zase
rine
But
ylbe
nzyl
phth
alat
ey C
hlor
endi
cac
idz
Cin
nam
ylan
thra
nila
tez
Clo
bra
tey
Dic
hlor
vosz
Eth
ylal
coho
ly H
ydro
chlo
ro
uoro
carb
on12
3IQ
HC
lM
alon
alde
hyde
sod
ium
saltz
MeA
-a-C
acet
atez
2-M
erca
ptob
enzo
thia
zole
y M
ethy
lclo
fena
pate
z N
-(N
-Met
hyl-
N-n
itros
ocar
bam
oyl)
-l-o
rnit
hine
4-(
Met
hyln
itro
sam
ino)
-1-(
3-py
ridy
l)-1
-but
anol
4-(
Met
hyln
itros
amin
o)-1
-( 3
-pyr
idyl
) -1-
( but
anon
e)N
afen
opin
Nitr
ofen
z To
luen
edi
isoc
yana
tec
omm
erci
algr
ade
( 24
( 80
) -an
d2
6( 2
0) -
)z1
23
-Tri
chlo
ropr
opan
ez
Peri
tone
alM
ouse
8B
is-1
2-(
chlo
rom
etho
xy) e
than
eB
is-1
4-(
chlo
rom
etho
xy) -
p-xy
lene
Bis
-(ch
loro
met
hyl)
ethe
rz C
hlor
opre
nez
tran
s-1
4-D
ichl
orob
uten
e-2
cavi
tyD
imet
hylc
arba
myl
chlo
ride
Phe
noxy
benz
amin
eH
Clz
Tri
s-1
23-
( chl
orom
etho
xy) p
ropa
neR
at22
Acr
onyc
ine
Acr
ylam
ide
Act
inom
ycin
DA
nili
neH
Cly
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
rom
ate
pota
ssiu
mz
Chl
oroz
otoc
in
Cyt
embe
nay
Dap
sone
y 1
2-D
ibro
moe
than
ez D
ibro
mom
anni
tolz
33
-Dim
ethy
lben
zidi
ne2
HC
lz 1
4-D
ioxa
nez
Eth
ylen
eox
idez
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Gly
cido
lz M
elph
alan
z N
-Met
hyl-
N4
-din
itros
oani
line
Mit
omyc
in-C
N-N
itro
so-2
24
-tri
met
hyl-
12-
dihy
droq
uino
line
poly
mer
Ph
enox
yben
zam
ine
HC
lz o-
Tolu
idin
eH
Clz
( Con
tinue
don
next
page
)
645
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Pitu
itar
ygl
and
Mou
se8
Die
thyl
stil
best
rolz
Eno
vid
Eth
ylen
eth
iour
eaz
Iodi
nate
dgl
ycer
olz
Isop
rene
Nor
lest
rinz
Pro
pylt
hiou
raci
lz Z
eara
leno
ney
Rat
73-
Am
inot
riaz
olez
12-
Dib
rom
oeth
anez
Die
thyl
stil
best
rolz
Eth
ylal
coho
ly 2-
Mer
capt
oben
zoth
iazo
ley
Met
roni
dazo
lez
Nor
lest
rinz
Pros
tate
Rat
4C
adm
ium
chlo
ride
N-N
itros
obis
( 2-h
ydro
xypr
opyl
) am
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
PhIP
HC
lz
Skin
Ham
ster
2U
reth
anez
Vin
ylch
lori
dez
Mou
se5
5-A
zacy
tidin
ez 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Chl
orop
rene
z G
lyci
dolz
Thi
o-te
paz
Rat
332-
Ace
tyla
min
ouo
rene
z 3-
Am
ino-
9-et
hylc
arba
zole
mix
ture
z 1-
Azo
xypr
opan
e2-
Azo
xypr
opan
eB
enze
nez
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
ol
tech
nica
lgra
dez
CI
dir
ectb
lue
15C
arbo
xym
ethy
lnitr
osou
rea
24-
Dia
min
oani
sole
sulf
atez
Dib
rom
odul
cito
lz D
ibro
mom
anni
tolz
Dim
etho
xane
2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 3
3-D
imet
hoxy
benz
idin
e-4
4-d
iisoc
yana
tey
33
-Dim
etho
xybe
nzid
ine
2HC
l3
3-D
imet
hylb
enzi
dine
2H
Clz
Dim
ethy
lvin
ylch
lori
dez
24-
Din
itro
tolu
ene
( con
tain
ing
10-
15
26-
dini
trot
olue
ne)z
1-E
thyl
nitr
oso-
3-( 2
-hyd
roxy
ethy
l)-u
rea
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Gly
cido
lz 1-
( 2-H
ydro
xyet
hyl)
-nit
roso
-3-e
thyl
urea
IQ
z L
asio
carp
ine
MeI
Qxz
N-(
N-M
ethy
l-N
-nitr
osoc
arba
moy
l)-l
-orn
ithi
ne
5-N
itro-
o-an
isid
inez
CI
aci
dre
d11
4p-
Ros
anili
neH
Clz
Thi
o-te
paz
Thi
oure
ay V
inyl
chlo
ride
z F
Damp
Cvi
olet
no1
y
Smal
lint
esti
neM
ouse
6C
apta
folz
Cap
tanz
N-E
thyl
-N-n
itro
-N-n
itro
sogu
anid
ine
Hyd
roge
npe
roxi
deN
-Met
hyl-
N-n
itro-
N-n
itros
ogua
nidi
nez
N-(
Tri
chlo
rom
ethy
lthi
o)ph
thal
imid
eM
onke
y1
Ure
than
ez
Rat
29A
cryl
onitr
ile
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
is( 2
3-d
ibro
mop
ropy
l)ph
osph
ate
mag
nesi
umsa
lt4
-Bis
( 2-h
ydro
xyet
hyl)
amin
o-2-
( 5-n
itro
-2-t
hien
yl) q
uina
zolin
eC
Id
irec
tblu
e15
Car
boxy
met
hyln
itros
oure
a1-
( 4-C
hlor
ophe
nyl)
-1-p
heny
l-2-
prop
ynyl
carb
amat
e2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 3
3-D
imet
hoxy
benz
idin
e2H
Cl
46-
Dim
ethy
l-2-
( 5-n
itro
-2-f
uryl
)py
rim
idin
etr
ans-
2-[(
Dim
ethy
lam
ino)
met
hylim
ino]
-5-[
2-( 5
-nit
ro-2
-fur
yl) v
inyl
] -1
34-
oxad
iazo
le3
3-D
imet
hylb
enzi
dine
2H
Clz
Z-E
thyl
-ON
N-a
zoxy
met
hane
1-E
thyl
-1-n
itros
oure
aFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z G
lu-P
-1z
Glu
-P-2
z IQ
z L
asio
carp
ine
N-M
ethy
l-N
-nitr
o-N
-nitr
osog
uani
dine
z N
-[5-
( 5-N
itro-
2-fu
ryl)
-13
4-t
hiad
iazo
l-2-
yl] a
ceta
mid
ez N
-Nitr
oso-
N-i
sobu
tylu
rea
3-N
itro
so-2
-oxa
zoli
dino
neN
itro
soet
hylu
reth
ane
PhI
PH
Clz
Pro
pane
sulto
neQ
uerc
etin
y C
Ia
cid
red
114
Trp
-P-2
acet
atez
Sple
enR
at7
Ani
line
HC
ly A
zobe
nzen
ey p-
Chl
oroa
nili
neH
Clz
Dap
sone
y o-
Nitr
osot
olue
neD
ampC
red
no9
y o-
Tolu
idin
eH
Clz
Stom
ach
Ham
ster
18A
F-2z
14-
Din
itros
o-2
6-di
met
hylp
iper
azin
eFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z H
ydra
zine
z N
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
N-[
4-( 5
-Nitr
o-2-
fury
l)-2
-thi
azol
yl] a
ceta
mid
eN
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] for
mam
idez
N-N
itro
so-2
3-d
ihyd
roxy
prop
yl-2
-hyd
roxy
prop
ylam
ine
Nitr
oso-
23-
dihy
drox
ypro
pyl-
2-ox
opro
pyla
min
eN
-Nitr
oso-
ethy
l-2-
oxop
ropy
lure
aN
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aN
itros
o-5-
met
hylo
xazo
lidon
eN
-Nit
roso
-N-m
ethy
lure
than
N-N
itros
o-1
3-ox
azol
idin
eN
-Nit
roso
-2-p
heny
leth
ylur
ea1
-Nit
roso
-34
5-t
rim
ethy
lpip
eraz
ine
Ure
than
ez V
inyl
chlo
ride
z
Mou
se63
Ace
tald
ehyd
em
ethy
lfor
myl
hydr
azon
eA
ciu
orfe
nA
F-2
z 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 2-
Am
ino-
4-( 5
-nitr
o-2-
fury
l)th
iazo
lez
tran
s-5-
Am
ino-
3[2-
( 5-n
itro-
2-fu
ryl)
viny
l] -1
24-
oxad
iazo
leA
reco
line
HC
lB
enza
ldeh
ydey
Ben
zofu
ranz
Ben
zotr
ichl
orid
eB
enzy
lace
tate
y B
enzy
lchl
orid
ey B
rom
oeth
anol
13
-But
adie
nez
But
ylat
edhy
drox
yani
sole
z 1
1-di
-N-B
utyl
hydr
azin
eC
affe
icac
idz
Cap
tafo
lz C
arba
zole
Cat
echo
lz 3-
Chl
oro-
2-m
ethy
lpro
pene
tec
hnic
algr
ade
( con
tain
ing
5di
met
hylv
inyl
chlo
ride
)z3
-(C
hlor
omet
hyl)
pyri
dine
HC
lz C
hlor
opre
nez
2-C
hlor
opro
pana
l1-
Chl
orop
rope
neC
ypro
tero
neac
etat
e1
1-D
ially
lhyd
razi
ne1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dic
hlor
vosz
Dig
lyci
dylr
esor
cino
leth
ert
echn
ical
grad
ez D
imet
hylv
inyl
chlo
ride
z D
init
roso
pipe
razi
neE
stra
diol
mus
tard
y E
thyl
acry
late
z Fo
rmic
acid
2-[ 4
-( 5
-nit
ro-2
-fur
yl) -
2-th
iazo
lyl] h
ydra
zide
z G
lyci
dolz
2-H
ydra
zino
-4-(
5-ni
tro-
2-fu
ryl)
thia
zole
z N
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
ICI
1628
46z
IQz
Isop
rene
Lov
asta
tin
MeI
Q1
-Met
hyl-
14-
dihy
dro-
7-[ 2
-(5-
nitr
ofur
yl) v
inyl
] -4-
oxo-
18-
naph
thyr
idin
e-3-
carb
oxyl
ate
pota
ssiu
m3
-(5-
Nitr
o-2-
fury
l)-
imid
azo(
12-
a) p
yrid
inez
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
N-[
4-( 5
-Nitr
o-2-
fury
l)-2
-thi
azol
yl] f
orm
amid
ez N
-Nit
roso
-N
-met
hylu
reaz
Nit
roso
dibu
tyla
min
ez N
-Nit
roso
hexa
met
hyle
neim
ine
N-N
itros
opip
erid
inez
b-P
ropi
olac
tone
z Se
sam
olz
Sty
rene
oxid
ez Te
lone
IIt
echn
ical
grad
ez N
-(T
rich
loro
met
hylth
io) p
htha
limid
e1
23-
Tri
chlo
ropr
opan
ez 2
22-
Tri
uo
ro-N
-[4-
( 5-n
itro
-2-f
uryl
) -2-
thia
zoly
l]ac
etam
idez
Tri
ur
alin
tec
hnic
algr
adey
Tri
s(2-
chlo
roet
hyl)
phos
phat
ez T
ris(
23-
dibr
omop
ropy
l)ph
osph
atez
Vin
ylac
etat
ez
Rat
85A
ceto
ne[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zone
1-A
ceto
xysa
frol
ey A
cryl
onitr
ile
1-A
llyl
-1-n
itro
sour
ea2
-Am
ino-
5-( 5
-nit
ro-2
-fur
yl) -
13
4-ox
adia
zole
2-
Am
ino-
5-( 5
-nitr
o-2-
fury
l)-1
34
-thi
adia
zole
2-A
min
o-4-
( 5-n
itro
-2-f
uryl
) thi
azol
ez 1-
Am
yl-1
-nit
roso
urea
Ari
stol
ochi
cac
id
sodi
umsa
lt( 7
7A
AI
21
AA
II)
Ben
zene
z B
enzo
( a) p
yren
ez 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bis
( 23
-dib
rom
opro
pyl)
phos
phat
em
agne
sium
salt
BL
-634
1H
Cl
N-n
-But
yl-N
-nitr
osou
rea
But
ylat
edhy
drox
yani
sole
z b
-But
yrol
acto
neC
affe
icac
idz
Cat
echo
lz 3-
Chl
oro-
2-m
ethy
lpro
pene
tec
hnic
algr
ade
( con
tain
ing
5di
met
hylv
inyl
chlo
ride
)z4
-Chl
oro-
o-ph
enyl
ened
iam
inez
Chl
oro
uoro
met
hane
3-
( Chl
orom
ethy
l)py
ridi
neH
Clz
Cip
rob
rate
z C
upfe
rron
z 1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
Dig
lyci
dylr
esor
cino
leth
ert
echn
ical
grad
ez 2
5-D
imet
hoxy
-4-a
min
osti
lben
ez D
imet
hylh
ydro
gen
phos
phit
ey 4
6-D
imet
hyl-
2-( 5
-nit
ro-2
-fu
ryl)
pyri
mid
ine
tran
s-2-
[(D
imet
hyla
min
o)m
ethy
limin
o]-5
-[2-
( 5-n
itro
-2-f
uryl
) vin
yl] -
13
4-ox
adia
zole
Dim
ethy
lvin
ylch
lori
dez
Epi
chlo
rohy
drin
y E
thyl
acry
late
z E
thyl
ene
oxid
ez 2-
Flu
oroe
thyl
-nitr
osou
rea
Gly
cido
lz N
-Hex
ylni
tros
oure
a1-
Hyd
roxy
anth
raqu
inon
e1-
( 2-H
ydro
xyet
hyl)
-1-
nitr
osou
reaz
1-( 3
-Hyd
roxy
prop
yl) -
1-ni
tros
oure
a1
-Hyd
roxy
safr
olez
ICI
1628
46z
Lox
tidin
eL
upit
idin
e3H
Cl
Mer
curi
cch
lori
dey
3-M
etho
xyca
tech
ol4
-Met
hoxy
phen
olN
-Met
hyl-
N-n
itro-
N-n
itros
ogua
nidi
nez
N-M
ethy
l-N
-nit
roso
benz
amid
e4-
Met
hylc
atec
hol
Met
hyln
itro
socy
anam
ide
3-( 5
-Nit
ro-2
-fur
yl) -
imid
azo(
12-
a) p
yrid
inez
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
4-( 5
-Nit
ro-2
-fur
yl) t
hiaz
ole
2-N
itro
uo
rene
8-N
itro
quin
olin
eN
itro
so-B
aygo
nN
-Nit
roso
-23
-dih
ydro
xypr
opyl
-2-h
ydro
xypr
opyl
amin
eN
itros
o-2
3-di
hydr
oxyp
ropy
l-2-
oxop
ropy
lam
ine
1-N
itro
so-3
5-d
imet
hyl-
4-be
nzoy
lpip
eraz
ine
N-N
itro
so-N
-met
hyl-
N-d
odec
ylam
ine
Nitr
oso-
N-m
ethy
l-N
-(2-
phen
yl) e
thyl
amin
eN
-Nit
roso
-N-m
ethy
ldec
ylam
ine
N-N
itro
so-N
-met
hylu
reaz
Nit
roso
-12
36
-tet
rahy
drop
yrid
ine
N-N
itro
sobe
nzth
iazu
ron
Nitr
osod
ibut
ylam
inez
N-N
itros
odie
thyl
amin
eN
-Nit
roso
ephe
drin
eN
itros
oeth
ylur
etha
nO
mep
razo
ley
Phen
acet
inz
Piv
alol
acto
ney
b-P
ropi
olac
tone
z N
-Pro
pyl-
N-n
itro
-N-n
itro
sogu
anid
ine
12-
Pro
pyle
neox
idez
Ses
amol
z St
yren
eox
idez
Sulf
alla
tez
Telo
neII
tec
hnic
algr
adez
12
3-T
rich
loro
prop
anez
24
6-T
rim
ethy
lani
line
HC
lz
646
Subc
utan
eous
Mou
se4
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 1
2-D
ibro
moe
than
ez N
2-c
-Glu
tam
yl-p
-hyd
razi
nobe
nzoi
cac
idG
lyci
dolz
tissu
eR
at13
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 2
4-D
iam
inot
olue
ne2
HC
lz 1
2-D
ichl
oroe
than
ez D
imet
hoxa
ne1
4-D
ioxa
nez
MeA
-a-C
acet
atez
44
-Met
hyle
ne-b
is( 2
-met
hyla
nili
ne)
o-N
itro
soto
luen
ep-
Ros
anili
neH
Clz
Tolu
ene
diis
ocya
nate
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
o-T
olui
dine
HC
lz 2
45-
Tri
met
hyla
nilin
eH
Clz
25-
Xyl
idin
eH
Clz
Test
isM
ouse
4D
ieth
ylst
ilbe
stro
lz Fi
nast
erid
eR
eser
pine
z Ta
mox
ifen
citr
atez
Rat
185-
Aza
cytid
inez
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 1
3-B
utad
iene
z N
-But
yl-N
-(4-
hydr
oxyb
utyl
) nitr
osam
ine
Cad
miu
mch
lori
de
2-C
hlor
o-1
11-
tri
uoro
etha
ne1
1-D
ichl
oro-
1-u
oroe
than
eH
ydro
chlo
rou
oroc
arbo
n12
3M
ethy
lter
t-bu
tyle
ther
z M
ethy
lclo
fena
pate
z M
etro
nida
zole
z N
-Nit
roso
dim
ethy
lam
inez
Oxo
linic
acid
y SD
Z20
0-11
01
11
2-Te
tra
uoro
etha
ney
Tri
chlo
roet
hyle
nez
Tri
nitr
ogly
ceri
nV
inyl
chlo
ride
z
Thy
roid
glan
dH
amst
er4
Hex
achl
orob
enze
nez
Hyd
razi
nez
Met
hylt
hiou
raci
lU
reth
anez
Mou
se18
3-A
min
o-4-
etho
xyac
etan
ilide
y H
Cbl
ueno
1z
tert
-But
ylal
coho
lz C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
24
-Dia
min
oani
sole
sulf
atez
Die
thyl
stil
best
rolz
Dox
ylam
ine
succ
inat
ez E
thio
nam
idey
Eth
ylen
eth
iour
eaz
44
-Met
hyle
nedi
anil
ine
2HC
lz 1
5-N
apht
hale
nedi
amin
ez N
itrob
enze
nez
Oxa
zepa
my
44
-Oxy
dian
iline
z C
Ip
igm
entr
ed3z
Sulf
amet
hazi
ne2
37
8-T
etra
chlo
rodi
benz
o-p-
diox
inz
44
-Thi
odia
nilin
ez
Rat
33A
cryl
amid
e3-
Am
inot
riaz
olez
o-A
nisi
dine
HC
lz B
emit
radi
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bro
mat
epo
tass
ium
z C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
Chl
orop
rene
z 2
4-D
iam
inoa
niso
lesu
lfat
ez N
N-D
ieth
ylth
iour
eay
1-E
thyl
-1-n
itro
sour
ea
Eth
ylen
eth
iour
eaz
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Flu
vast
atin
Gly
cido
lz Io
dina
ted
glyc
erol
z Is
obut
eney
Mal
onal
dehy
des
odiu
msa
ltz
Met
him
azol
e4
4-M
ethy
lene
bis(
NN
-dim
ethy
l)be
nzen
amin
ez 4
4-M
ethy
lene
dian
iline
2H
Clz
Mir
exp
hoto
-N
itro
benz
enez
N-N
itro
sobi
s(2-
oxop
ropy
l)am
ine
44
-Oxy
dian
iline
z Pr
opyl
thio
urac
ilz p-
Ros
anil
ine
HC
lz 2
37
8-Te
trac
hlor
odib
enzo
-p-d
ioxi
nz 4
4-T
hiod
iani
linez
Thi
oura
cilz
Tri
met
hylt
hiou
reay
Vin
ylac
etat
ez Z
inc
dim
ethy
ldith
ioca
rbam
atez
Uri
nary
blad
der
Dog
23
3-D
ichl
orob
enzi
dine
44
-Met
hyle
ne-b
is( 2
-chl
oroa
nilin
e)H
amst
er3
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-t
hiaz
olyl
] hyd
razi
dez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
acet
amid
eN
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] for
mam
idez
Mou
se12
2-A
cety
lam
ino
uore
nez
4-A
min
odip
heny
l2-
Am
inod
iphe
nyle
neox
ide
o-A
nisi
dine
HC
lz 4-
Chl
oro-
4-a
min
odip
heny
leth
erz
p-C
resi
dine
z 4-
Eth
ylsu
lpho
nyln
apht
hale
ne-1
-sul
fona
mid
eN
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez P
hena
cetin
z Te
lone
IIt
echn
ical
grad
ez U
raci
lz
Mon
key
12-
Nap
hthy
lam
inez
Rat
49A
ceta
min
ophe
nz A
llyli
soth
iocy
anat
ey 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 2-
Am
ino-
4-( 5
-nitr
o-2-
fury
l)th
iazo
lez
4-A
min
o-2-
nitr
ophe
noly
11-A
min
ound
ecan
oic
acid
y o-
Ani
sidi
neH
Clz
Ari
stol
ochi
cac
ids
odiu
msa
lt( 7
7A
AI
21
AA
II)
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez C
Id
ispe
rse
blue
1y N
-But
yl-N
-(4-
hydr
oxyb
utyl
) nitr
osam
ine
4-C
hlor
o-o-
phen
ylen
edia
min
ez m
-Cre
sidi
ney
p-C
resi
dine
z C
yclo
phos
pham
idez
Die
thyl
ene
glyc
olD
imet
hyla
rsin
icac
idy
Fose
tylA
lIQ
HC
lM
eA-a
-Cac
etat
ez M
elam
iney
2-M
etho
xy-3
-am
inod
iben
zofu
ran
2-N
apht
hyla
min
ez N
itril
otri
acet
icac
idz
Nitr
ilot
riac
etic
acid
tri
sodi
umsa
ltm
onoh
ydra
tey
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez o-
Nitr
oani
sole
z N
-Nitr
oso-
N-m
ethy
l-N
-dod
ecyl
amin
eN
-Nitr
oso-
N-m
ethy
l-N
-tet
rade
cyla
min
eN
-Nit
roso
-N-m
ethy
ldec
ylam
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
Nitr
osod
ibut
ylam
inez
N-N
itro
sodi
phen
ylam
iney
o-N
itros
otol
uene
N-O
xydi
ethy
lene
thio
carb
amyl
-N-o
xydi
ethy
lene
sulf
enam
ide
Phe
nace
tinz
Phen
azon
eo-
Phen
ylph
enat
eso
dium
y o-
Phen
ylph
enol
y P
otas
sium
bica
rbon
ate
Purp
urin
Que
rcet
iny
p-Q
uino
nedi
oxim
ey Sa
ccha
rin
sodi
umy
Sali
cyla
zosu
lfap
yrid
inez
o-To
luen
esul
fona
mid
eo-
Tolu
idin
eH
Clz
Trp
-P-2
acet
atez
Ura
cilz
Ute
rus
Ham
ster
1N
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aM
ouse
12B
rom
oeth
anez
Chl
oroe
than
ey D
acar
bazi
nez
12-
Dic
hlor
oeth
anez
Die
thyl
stil
best
rolz
Eth
ylen
eox
idez
Gly
cido
lz ( N
-6) -
( Met
hyln
itros
o)ad
enos
ine
Proc
arba
zine
HC
lz 1
23-
Tri
chlo
ropr
opan
ez T
rim
ethy
lpho
spha
tey
Vin
ylac
etat
ez
Rat
26A
cryl
amid
e1-
Ally
l-1-
nitr
osou
rea
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
1-A
myl
-1-n
itros
oure
aA
traz
iney
CI
dir
ectb
lue
15B
rom
ocri
ptin
em
esyl
atey
N-n
-But
yl-N
-nit
roso
urea
Cal
cium
valp
roat
eC
apta
nz 2-
Chl
oro-
11
1-tr
iuo
roet
hane
Dac
arba
zine
z D
amin
ozid
ez 3
3-D
imet
hoxy
benz
idin
e-4
4-d
iisoc
yana
tey
33
-Dim
etho
xybe
nzid
ine
2HC
lD
imet
hyla
min
oeth
ylni
tros
oeth
ylur
ean
itri
tesa
lt1-
Eth
ylni
tros
o-3-
( 2-h
ydro
xyet
hyl)
-ure
a1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
N-H
exyl
nitr
osou
rea
ICR
F-1
59z
Isop
hosp
ham
idez
15-
Nap
htha
lene
diam
inez
Nit
robe
nzen
ez N
orle
stri
nz 4
4-T
hiod
iani
linez
Vin
ylac
etat
ez
Vag
ina
Mou
se1
AZ
Tz
Rat
2A
ZT
z N
-n-B
utyl
-N-n
itro
sour
ea( C
ontin
ued
onne
xtpa
ge)
647
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Vas
cula
rsy
stem
Ham
ster
91
2-D
imet
hylh
ydra
zine
2H
Cl
Gly
cido
lz H
exac
hlor
oben
zene
z N
-Nit
roso
-eth
yl-2
-oxo
prop
ylur
eaN
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aN
-Nitr
oso-
oxop
ropy
lchl
oroe
thyl
urea
N-N
itro
so-o
xopr
opyl
urea
N-N
itros
o-2-
phen
ylet
hylu
rea
Vin
ylch
lori
dez
Mou
se59
A-a
-CN
-Ace
tyl-
4-( h
ydro
xym
ethy
l)ph
enyl
hydr
azin
e1-
Ace
tyl-
2-ph
enyl
hydr
azin
eA
llyl
hydr
azin
eH
Cl
Are
colin
eH
Cl
Aza
thio
prin
eB
enzi
dine
2H
Cl
2-B
iphe
nyla
min
eH
Cly
13-
But
adie
nez
Cap
tafo
lz C
arba
myl
hydr
azin
eH
Cl
4-C
hlor
o-4
-am
inod
iphe
nyle
ther
z 1-
Chl
oro-
4-ni
trob
enze
ney
5-C
hlor
o-o-
tolu
idin
ey 4-
Chl
oro-
o-to
luid
ine
HC
ly p-
Chl
oroa
nilin
eH
Clz
Chl
orop
rene
z C
upfe
rron
z D
acar
bazi
nez
Dam
inoz
idez
24-
Dia
min
otol
uene
2H
Clz
12-
Dib
rom
oeth
anez
Dif
talo
ne7
12-
Dim
ethy
lben
z(a)
anth
race
ne1
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
N-E
thyl
-N-f
orm
ylhy
draz
ine
Eth
ylhy
draz
ine
HC
lG
lu-P
-1z
Glu
-P-2
z p-
Hyd
razi
nobe
nzoi
cac
idH
Cl
1-H
ydro
xysa
frol
ez Is
opre
neM
eA-a
-Cac
etat
ez N
-Met
hyl-
N-f
orm
ylhy
draz
ine
2-M
ethy
l-1-
nitr
oant
hraq
uino
nez
Mic
hler
rsquoske
tone
z 5-
Nitr
o-o-
tolu
idin
ey N
itro
fenz
N-N
itros
o-N
-met
hylu
reaz
Pent
achl
oroa
niso
lez
23
45
6-Pe
ntac
hlor
ophe
nol(
Dow
icid
eE
C-7
)y2
34
56
-Pen
tach
loro
phen
olt
echn
ical
grad
ez n-
Pen
tylh
ydra
zine
HC
lPh
enyl
ethy
lhyd
razi
nesu
lfat
ePh
enyl
hydr
azin
eH
Cl
Ster
igm
atoc
ysti
nz Te
tra
uoro
ethy
lene
z To
luen
edi
isoc
yana
tec
omm
erci
algr
ade
( 24
( 80
) -an
d2
6( 2
0) -
)zo
-Tol
uidi
neH
Clz
24
6-T
rich
loro
anil
iney
24
5-T
rim
ethy
lani
line
HC
lz 2
46-
Tri
met
hyla
nili
neH
Clz
Ure
than
ez V
inyl
carb
amat
eV
inyl
chlo
ride
z V
inyl
uor
idez
Vin
ylid
ene
chlo
ride
y 2
5-X
ylid
ine
HC
lz
Mon
key
2A
ato
xin
B1y
Ure
than
ez
Rat
32A
nilin
eH
Cly
Azo
benz
eney
Ben
zene
z C
livor
ine
Cup
ferr
onz
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
Z-E
thyl
-ON
N-a
zoxy
etha
neZ
-Eth
yl-O
NN
-azo
xym
etha
neI
QH
Cl
Las
ioca
rpin
e4
4-M
ethy
lene
-bis
( 2-c
hlor
oani
line)
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
N-N
itros
o-( 2
-hyd
roxy
prop
yl) -
( 2-h
ydro
xyet
hyl)
amin
eN
itro
so-1
23
6-t
etra
hydr
opyr
idin
eN
-Nitr
osob
is( 2
-oxo
prop
yl) a
min
eN
-Nit
roso
diet
hano
lam
ine
N-N
itro
sodi
ethy
lam
ine
N-N
itros
odim
ethy
lam
inez
N-N
itros
omet
hyl-
( 2-t
osyl
oxye
thyl
) am
ine
N-N
itros
omor
phol
ine
N-N
itro
sopy
rrol
idin
ez Pe
tasi
teni
neS
teri
gmat
ocys
tinz
Sym
phyt
ine
Tetr
auo
roet
hyle
nez
o-To
luid
ine
HC
lz T
rp-P
-2ac
etat
ez V
inyl
brom
ide
Vin
ylch
lori
dez
Vin
yl
uori
dez
aT
here
was
nore
port
edta
rget
site
in1
spec
ies
( rat
sor
mic
e)fo
r5
chem
ical
sw
ithsu
pers
crip
tsb
utth
ech
emic
alw
asev
alua
ted
byth
epu
blis
hed
auth
oras
aca
rcin
ogen
ald
rinz
diel
drin
z N
-nit
roso
pyrr
olid
inez
23
45
6-pe
ntac
hlor
ophe
nol
( Dow
icid
eE
C-7
)ya
ndur
etha
nez
bN
asal
cavi
tyin
clud
estis
sues
ofth
eno
sen
asal
turb
inat
esp
aran
asal
sinu
ses
and
trac
hea
c Ora
lcav
ityin
clud
estis
sues
ofth
em
outh
oro
phar
ynx
phar
ynx
and
lary
nx
Ach
emic
alis
liste
dun
der
each
orga
nev
alua
ted
aspo
sitiv
ein
anex
peri
men
tin
that
spec
ies
byat
leas
t1au
thor
The
refo
rea
chem
ical
may
beli
sted
unde
rse
vera
ltar
geto
rgan
san
dev
ery
chem
ical
liste
din
the
tabl
eis
posi
tive
inat
leas
t1sp
ecie
sIn
orde
rto
com
pare
resu
ltsin
rats
and
mic
esy
mbo
lsfo
llow
chem
ical
ste
sted
inbo
thsp
ecie
sa
zin
dica
tes
that
the
chem
ical
ispo
sitiv
eat
som
esi
tein
both
spec
ies
and
ay
indi
cate
sth
atit
was
test
edin
both
butp
ositi
vein
only
1a
Nth
enu
mbe
rof
chem
ical
sw
ithat
leas
t1po
sitiv
ete
stat
that
site
inth
atsp
ecie
sB
ecau
sem
any
chem
ical
sin
duce
tum
ors
atm
ore
than
1si
tein
agi
ven
spec
ies
man
ych
emic
als
appe
arm
ore
than
once
inth
eta
ble
648
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649
species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters
RESULTS IN RATS AND MICE
For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens
TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database
Chemicals evaluated as carcinogenic in
Rats Mice
All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)
Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2
a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not
b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats
All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical
to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included
The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site
Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common
650 GOLD ET AL TOXICOLOGIC PATHOLOGY
TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)
Target site Agent mixture or industrial process
Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e
Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke
Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products
Brain Vinyl chloride a
Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e
Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena
Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system
Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as
a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell
lymphotropic virus type I (HTLV-I) Vinyl chloridea
Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production
Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)
Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea
Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea
Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)
Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea
Mesenchymal tumors Azathioprinea
Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust
Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust
Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid
(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke
Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production
8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots
Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e
Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays
IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD
IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no
tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance
is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651
sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites
Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to
be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)
Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)
Target Organs of Human CarcinogensTo complement the compendium of target organs in car-
cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke
In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)
Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens
Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from
bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)
ACKNOWLEDGMENTS
We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention
REFERENCES
1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56
2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600
3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998
4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685
5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404
6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605
7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246
8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100
9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash
23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC
11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the
652 GOLD ET AL TOXICOLOGIC PATHOLOGY
US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240
12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute
13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program
14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX
15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11
16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash
34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c
Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
N-N
itro
so-N
-met
hyld
ecyl
amin
e3-
Nit
roso
-2-o
xazo
lidin
one
Nit
roso
-2-o
xopr
opyl
etha
nola
min
eN
itro
so-1
23
6-t
etra
hydr
opyr
idin
eN
-Nit
roso
ally
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itro
soal
lyl-
2-ox
opro
pyla
min
eN
-Nitr
osoa
llyl
etha
nola
min
eN
-Nit
roso
bis(
2-ox
opro
pyl)
amin
eN
itro
sodi
buty
lam
inez
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
diet
hyla
min
eN
-Nitr
osod
imet
hyla
min
ez p-
Nitr
osod
iphe
nyla
min
ez N
-Nit
roso
dipr
opyl
amin
eN
itros
odod
ecam
ethy
lene
imin
eN
-Nit
roso
ephe
drin
eN
itro
soet
hylm
ethy
lam
ine
Nitr
osoh
epta
met
hyle
neim
ine
N-N
itros
omet
hyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nit
roso
met
hyl-
( 2-h
ydro
xyet
hyl)
amin
eN
-Nitr
osom
ethy
l-( 3
-hyd
roxy
prop
yl) a
min
eN
-Nitr
osom
ethy
l(2-
oxop
ropy
l)am
ine
N-N
itro
som
ethy
l-( 2
-tos
ylox
yeth
yl) a
min
eN
itro
som
ethy
lund
ecyl
amin
eN
-Nit
roso
mor
phol
ine
N-N
itros
opip
erid
inez
N-N
itro
sopy
rrol
idin
ez N
-Nit
roso
thia
ldin
eo-
Nit
roso
tolu
ene
Nor
lest
rinz
N-(
9-O
xo-2
-uo
reny
l)ac
etam
ide
44
-Oxy
dian
iline
z 2
34
56-
Pent
achl
orop
heno
lte
chni
calg
rade
z P
etas
iten
ine
Phe
noba
rbit
als
odiu
mz
1-P
heny
lazo
-2-n
apht
holy
o-P
heny
lene
diam
ine
2HC
lz P
iper
onyl
buto
xide
z P
olyb
rom
inat
edbi
phen
ylm
ixtu
rez
Pre
dnis
olon
eP
yril
amin
em
alea
tey
CI
aci
dre
d11
4C
Ip
igm
entr
ed3z
Damp
Cre
dno
5z
Damp
Cre
dno
9y
FD
ampC
red
no1
p-
Ros
anili
neH
Clz
Saf
role
z Se
leni
umsu
lde
z Se
nkir
kine
Ste
rigm
atoc
ystin
z S
ymph
ytin
eTa
mox
ifen
citr
atez
Telo
neII
tec
hnic
algr
adez
33
44
-Te
traa
min
obip
heny
l4H
Clz
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tetr
auo
roet
hyle
nez
Thi
oace
tam
idez
44
-Thi
odia
nilin
ez To
luen
edi
isoc
yana
te
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
Tri
amci
nolo
neac
eton
ide
24
5-T
rim
ethy
lani
line
z 2
45-
Tri
met
hyla
nili
neH
Clz
24
6-T
rim
ethy
lani
line
HC
lz T
rini
trog
lyce
rin
Trp
-P-1
acet
atez
Trp
-P-2
acet
atez
Vin
ylac
etat
ez V
inyl
brom
ide
Vin
ylch
lori
dez
Vin
yl
uori
dez
CI
dis
pers
eye
llow
3z
Tre
esh
rew
1A
ato
xin
B1y
Lun
gH
amst
er3
Met
hyln
itro
sam
ino-
NN
-dim
ethy
leth
ylam
ine
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
1-N
itro
so-3
45
-tri
met
hylp
iper
azin
eM
ouse
116
Ace
tald
ehyd
em
ethy
lfor
myl
hydr
azon
eN
-Ace
tyl-
4-( h
ydro
xym
ethy
l)ph
enyl
hydr
azin
e1-
Ace
tyl-
2-is
onic
otin
oylh
ydra
zine
A
llyl
hydr
azin
eH
Cl
1-A
min
o-2
4-di
brom
oant
hraq
uino
nez
Are
coli
neH
Cl
5-A
zacy
tidi
nez
Ben
zene
z B
enzo
fura
nz B
enzo
tric
hlor
ide
Ben
zoyl
hydr
azin
eB
enzy
lhyd
razi
ne2
HC
l2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bis
( 2-c
hlor
o-1-
met
hyle
thyl
) eth
er
tech
nica
lgra
dey
Bis
-(ch
loro
met
hyl)
ethe
rz 1
3-B
utad
iene
z N
-n-B
utyl
-N-f
orm
ylhy
draz
ine
But
ylat
edhy
drox
ytol
uene
y 1
1-di
-n-B
utyl
hydr
azin
en-
But
ylhy
draz
ine
HC
l1
2-di
-N-B
utyl
hydr
azin
e2H
Cl
Caf
feic
acid
z C
arba
myl
hydr
azin
eH
Cl
1-C
arba
myl
-2-p
heny
lhyd
razi
neC
hlor
ambu
cilz
Chl
orop
rene
z C
obal
tsul
fate
hept
ahyd
rate
z C
oum
arin
z C
yclo
phos
pham
idez
Dac
arba
zine
z D
amin
ozid
ez p
p-D
DD
y D
DT
z 1
1-D
iall
ylhy
draz
ine
12-
Dia
llyl
hydr
azin
e2H
Cl
Dib
enz(
ah)
anth
race
ne1
2-D
ibro
mo-
3-ch
loro
prop
anez
Dib
rom
odul
cito
lz 1
2-D
ibro
moe
than
ez D
ibro
mom
anni
tolz
12-
Dic
hlor
oeth
anez
12-
Dif
orm
ylhy
draz
ine
Dih
ydro
safr
olez
25-
Dim
etho
xy-4
-am
inos
tilbe
nez
33
-Dim
ethy
lben
zidi
ne2
HC
lz 1
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
a-E
cdys
one
Est
radi
olm
usta
rdy
N-E
thyl
-N-f
orm
ylhy
draz
ine
Eth
ylen
eim
ine
Eth
ylen
eox
idez
Eth
ylhy
draz
ine
HC
l5-
Flu
orou
raci
ly Fo
rmyl
hydr
azin
eG
lyci
dolz
c-1
23
45
6-H
exac
hlor
ocyc
lohe
xane
y H
exan
alm
ethy
lfor
myl
hydr
azon
eH
ydra
zine
z H
ydra
zine
sulf
atez
IQz
Isob
utyl
nitr
itez
Ison
iazi
dz Is
onic
otin
icac
idva
nilly
liden
ehyd
razi
de
Isop
rene
Lov
asta
tinM
eIQ
xz M
elph
alan
z 1-
Met
hyl-
14-
dihy
dro-
7-[ 2
-(5-
nitr
ofur
yl) v
inyl
] -4-
oxo-
18-
naph
thyr
idin
e-3-
carb
oxyl
ate
pota
ssiu
m
N-M
ethy
l-N
-for
myl
hydr
azin
eM
ethy
lmet
hane
sulf
onat
e3-
Met
hylb
utan
alm
ethy
lfor
myl
hydr
azon
eM
ethy
lene
chlo
ride
z M
ethy
lhyd
razi
ne
Met
hylh
ydra
zine
sulf
ate
( N-6
) -( M
ethy
lnit
roso
) ade
nine
(N
-6) -
( Met
hyln
itro
so) a
deno
sine
N-M
ethy
lola
cryl
amid
ey M
etro
nida
zole
z M
olyb
denu
mtr
ioxi
dey
Mon
oace
tylh
ydra
zine
Nap
htha
lene
15
-Nap
htha
lene
diam
inez
Nic
otin
icac
idhy
draz
ide
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez 3-
Nitr
o-3-
hexe
nez
Nit
robe
nzen
ez N
itrom
etha
nez
Nit
roso
dibu
tyla
min
ez N
-Nit
roso
dim
ethy
lam
inez
N-N
itros
ohex
amet
hyle
neim
ine
N-N
itro
sopi
peri
dine
z O
zone
y Pe
ntan
alm
ethy
lfor
myl
hydr
azon
en-
Pen
tylh
ydra
zine
HC
lPh
enes
teri
nz Ph
enyl
ethy
lhyd
razi
nesu
lfat
eP
roca
rbaz
ine
HC
lz N
-N-P
ropy
l-N
-for
myl
hydr
azin
eP
ropy
lhyd
razi
neH
Cl
Sel
eniu
msu
lde
z S
trep
tozo
toci
nz Su
lfal
late
z Te
lone
IIt
echn
ical
grad
ez 3
34
4-T
etra
amin
obip
heny
l4H
Clz
Tetr
anitr
omet
hane
z T-
2to
xin
Tri
chlo
roet
hyle
nez
Tri
ura
lint
echn
ical
grad
ey 2
45-
Tri
met
hyla
nilin
eH
Clz
Tri
s(2
3-di
brom
opro
pyl)
phos
phat
ez U
reth
anez
Vin
ylch
lori
dez
Vin
ylu
orid
ez V
inyl
iden
ech
lori
dey
24-
Xyl
idin
eH
Cly
Mon
key
1U
reth
anez
Rat
551-
Ally
l-1-
nitr
osou
rea
2-A
min
o-5-
( 5-n
itro
-2-f
uryl
) -1
34-
oxad
iazo
le2
-Am
ino-
5-( 5
-nitr
o-2-
fury
l)-1
34
-thi
adia
zole
2-A
min
o-5-
nitr
othi
azol
ey 1-
Am
yl-1
-nitr
osou
rea
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
is-(
chlo
rom
ethy
l)et
herz
HC
blue
no1
z B
rom
oeth
anez
N-n
-But
yl-N
-nit
roso
urea
Cad
miu
mch
lori
deC
adm
ium
sulp
hate
( 11
) 1-
Chl
oroe
thyl
nitr
oso-
3-( 2
-hyd
roxy
prop
yl) u
rea
Chl
orop
rene
z C
obal
tsul
fate
hept
ahyd
rate
z 1
2-D
ibro
moe
than
ez D
imet
hylh
ydro
gen
phos
phit
ey tr
ans-
2-[(
Dim
ethy
lam
ino)
met
hylim
ino]
-5-
[ 2-(
5-ni
tro-
2-fu
ryl)
viny
l] -1
34-
oxad
iazo
le3
3-D
imet
hylb
enzi
dine
2H
Clz
12-
Epo
xybu
tane
y 1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
N-H
exyl
nitr
osou
rea
Hyd
razi
nez
Hyd
razi
nesu
lfat
ez 1-
( 2-H
ydro
xyet
hyl)
-1-n
itro
sour
eaz
Isob
utyl
nitr
itez
Ison
iazi
dz 4
4-M
ethy
lene
-bi
s(2-
chlo
roan
iline
) 4-
( Met
hyln
itros
amin
o)-1
-(3-
pyri
dyl)
-1-b
utan
ol4
-(M
ethy
lnit
rosa
min
o)-1
-(3-
pyri
dyl)
-1-(
buta
none
) N
-[ 3
-(5-
Nitr
o-2-
fury
l)-
12
4-ox
adia
zole
-5-y
l] -m
ethy
lace
tam
ide
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
3-N
itro-
3-he
xene
z 5-
Nitr
oace
naph
then
ez N
-Nit
roso
-bis
-(4
44-
tri
uoro
-N-b
utyl
) am
ine
N-N
itros
o-N
-met
hyl-
N-d
odec
ylam
ine
N-N
itros
o-N
-met
hyl-
N-t
etra
decy
lam
ine
N-N
itro
so-N
-met
hyld
ecyl
amin
eN
-Nitr
oso-
N-m
ethy
lure
az N
-Nitr
osob
is( 2
-hyd
roxy
prop
yl)
amin
eN
-Nitr
osob
is-2
3-d
ihyd
roxy
prop
ylam
ine
( 2-o
xopr
opyl
) am
ine
Nitr
osod
ibut
ylam
inez
N-N
itros
odim
ethy
lam
inez
N-N
itro
soep
hedr
ine
Nitr
osoe
thyl
met
hyla
min
eN
-Nit
roso
met
hyl
N-N
itro
som
ethy
l-( 3
-hyd
roxy
prop
yl) a
min
eN
itro
som
ethy
lund
ecyl
amin
eC
Ia
cid
red
114
Sod
ium
dich
rom
ate
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tetr
anit
rom
etha
nez
24
5-T
rim
ethy
lani
line
z 2
46-
Tri
met
hyla
nili
neH
Clz
Vin
ylch
lori
dez
Mam
mar
ygl
and
Dog
1Ly
nest
reno
lH
amst
er1
Vin
ylch
lori
dez
Mou
se24
5-A
zacy
tidin
ez B
enze
nez
CI
dir
ectb
lack
381
3-B
utad
iene
z C
alci
fero
lC
hlor
opre
nez
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
Die
thyl
stilb
estr
olz
a-E
cdys
one
Est
radi
olE
thyl
ene
oxid
ez F
uros
emid
ey G
lyci
dolz
Gri
seof
ulvi
nIs
onia
zidz
Ison
icot
inic
acid
vani
llylid
eneh
ydra
zide
( N
-6) -
( Met
hyln
itros
o)ad
enos
ine
Nitr
oben
zene
z R
eser
pine
z Su
lfal
late
z V
inyl
chlo
ride
z V
inyl
uor
idez
Vin
ylid
ene
chlo
ride
y
644
Rat
102
4-A
cety
lam
inob
iphe
nyl
2-A
cety
lam
ino
uore
nez
Acr
onyc
ine
Acr
ylam
ide
Acr
ylon
itri
leA
F-2
z 1-
Ally
l-1-
nitr
osou
rea
2-A
min
o-5-
( 5-n
itro-
2-fu
ryl)
-13
4-
oxad
iazo
le2
-Am
ino-
5-( 5
-nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
e2-
Am
ino-
5-ni
trot
hiaz
oley
4-A
min
odip
heny
lHC
l1-
Am
yl-1
-nit
roso
urea
Atr
azin
ey B
emit
radi
ne
Ben
zidi
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
4-B
is( 2
-hyd
roxy
ethy
l)am
ino-
2-( 5
-nit
ro-2
-thi
enyl
) qui
nazo
line
13-
But
adie
nez
N-n
-But
yl-N
-nitr
osou
rea
Cap
tafo
lz C
arbo
nte
trac
hlor
idez
Car
boxy
met
hyln
itros
oure
aC
hlor
ambu
cilz
Chl
orop
rene
z C
ytem
bena
y D
acar
bazi
nez
N-1
-Dia
ceta
mid
ouo
rene
46
-Dia
min
o-2-
( 5-n
itro-
2-fu
ryl)
-S-t
riaz
ine
24-
Dia
min
oani
sole
sulf
atez
24-
Dia
min
otol
uene
z 1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dib
rom
oman
nito
lz 1
3-D
ibut
yl-1
-nit
roso
urea
33
-Dic
hlor
oben
zidi
ne1
2-D
ichl
oroe
than
ez 3
3-D
imet
hoxy
benz
idin
e2H
Cl
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
12-
Dim
ethy
l-5-
nitr
oim
idaz
ole
tran
s-2-
[(D
imet
hyla
min
o)m
ethy
limin
o]-5
-[2-
( 5-n
itro
-2-f
uryl
) vin
yl] -
13
4-ox
adia
zole
Dim
ethy
lam
inoe
thyl
nitr
osoe
thyl
urea
nitr
ite
salt
33
-Dim
ethy
lben
zidi
ne2
HC
lz 2-
( 22
-Dim
ethy
lhyd
razi
no) -
4-( 5
-nitr
o-2-
fury
l)th
iazo
le
24-
Din
itro
tolu
ene
( con
tain
ing
10-
15
24-
Dio
xane
z 1-
Eth
ylni
tros
o-3-
( 2-h
ydro
xyet
hyl)
-ure
a1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
6-di
nitr
otol
uene
)zN
-(2-
Fluo
reny
l)-2
22
-tri
uo
roac
etam
ide
Form
icac
id2-
( 4-m
ethy
l-2-
thia
zoly
l)hy
draz
ide
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-
thia
zoly
l] hyd
razi
dez
Gly
cido
lz H
exam
ethy
lmel
amin
eN
-Hex
ylni
tros
oure
a2-
Hyd
razi
no-4
-(p-
amin
ophe
nyl)
thia
zole
z 2-
Hyd
razi
no-4
-( 5
-nit
ro-2
-fur
yl) t
hiaz
olez
2-H
ydra
zino
-4-(
p-ni
trop
heny
l)th
iazo
lez
Hyd
razo
benz
enez
1-( 2
-Hyd
roxy
ethy
l)-3
-[( 5
-nit
rofu
rfur
ylid
ene)
amin
o]-2
-im
idaz
olid
inon
e1-
( 2-H
ydro
xyet
hyl)
-nit
roso
-3-e
thyl
urea
1-(
2-H
ydro
xyet
hyl)
-1-n
itros
oure
az In
dom
etha
cin
IQz
IQH
Cl
Ison
iazi
dz 2-
Met
hoxy
-3-a
min
odib
enzo
fura
n4-
Met
hyl-
1-[(
5-ni
trof
urfu
rylid
ene)
amin
o]-2
-im
idaz
olid
inon
eN
-(N
-Met
hyl-
N-n
itro
soca
rbam
oyl)
-l-o
rnit
hine
3-M
ethy
lcho
lant
hren
e4
4-M
ethy
lene
-bi
s(2-
chlo
roan
iline
) 4
4-M
ethy
lene
-bis
( 2-m
ethy
lani
line)
Met
hyle
nech
lori
dez
Met
roni
dazo
lez
l-5-
Mor
phol
inom
ethy
l-3-
[(5-
nitr
ofur
fury
lide
ne) a
min
o]-
2-ox
azol
idin
one
HC
lN
ithia
zide
z 5-
Nitr
o-2-
fura
ldeh
yde
sem
icar
bazo
nez
3-( 5
-Nitr
o-2-
fury
l)-i
mid
azo(
12-
a)
pyri
dine
z 4-
( 5-N
itro-
2-fu
ryl)
thia
zole
N
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] ace
tam
ide
NN
-[6-
( 5-N
itro
-2-f
uryl
) -S-
tria
zine
-24
-diy
l] bis
acet
amid
e5-
Nitr
oace
naph
then
ez 1-
[(5-
Nit
rofu
rfur
ylid
ene)
amin
o]-2
-im
idaz
olid
inon
eN
itrom
etha
nez
1-N
itrop
yren
eN
orle
stri
nz O
chra
toxi
nA
z N
-(9-
Oxo
-2-
uore
nyl)
acet
amid
ePh
enac
etin
z Ph
enes
teri
nz Ph
IPH
Clz
Proc
arba
zine
HC
lz Pr
opan
esu
lton
e1
2-Pr
opyl
ene
oxid
ez St
yren
ey Su
lfal
late
z 4
4-S
ulfo
nylb
isac
etan
ilid
eTo
luen
edi
isoc
yana
te
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
o-T
olui
dine
HC
lz 1
23-
Tri
chlo
ropr
opan
ez 2
22-
Tri
uor
o-N
-[4-
( 5-n
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] ace
tam
idez
Trp
-P-2
acet
atez
Vin
ylch
lori
dez
FD
ampC
viol
etno
1y
Mes
ovar
ium
Rat
2Sa
lbut
amol
Ter
buta
line
Myo
card
ium
Mou
se2
Est
radi
olm
usta
rdy
Phen
este
rinz
Nas
alca
vity
bB
ush
baby
1N
-Nitr
osod
ieth
ylam
ine
Ham
ster
11A
ceta
ldeh
yde
Dia
llyln
itros
amin
eD
imet
hylc
arba
myl
chlo
ride
Hyd
razi
nez
Met
hyln
itro
sam
ino-
NN
-dim
ethy
leth
ylam
ine
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
N-N
itro
soal
lyl-
2-ox
opro
pyla
min
eN
-Nitr
osom
ethy
l-2
3-di
hydr
oxyp
ropy
lam
ine
N-N
itros
omor
phol
ine
N-N
itros
onor
nico
tine
N-N
itros
opip
erid
inez
Mou
se6
Ally
lgly
cidy
leth
ery
12-
Dib
rom
o-3-
chlo
ropr
opan
ez 1
2-D
ibro
moe
than
ez Fo
rmal
dehy
dez
N-N
itro
sohe
xam
ethy
lene
imin
e1
2-Pr
opyl
ene
oxid
ez
Rat
43A
ceta
ldeh
yde
Acr
ylon
itril
e1-
Azo
xypr
opan
eB
enze
nez
Bis
-(ch
loro
met
hyl)
ethe
rz p-
Cre
sidi
nez
Dia
llyln
itros
amin
e1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dim
ethy
lnitr
amin
eD
imet
hylv
inyl
chlo
ride
z D
initr
osoh
omop
iper
azin
e1
4-D
ioxa
nez
12-
Epo
xybu
tane
y Z
-Eth
yl-O
NN
-azo
xyet
hane
E
thyl
benz
ene
Eth
ylni
tros
ocya
nam
ide
Form
alde
hyde
z H
exam
ethy
lpho
spho
ram
ide
Hyd
razi
nez
N-N
itro
so-N
-met
hyld
ecyl
amin
edi
( N-N
itro
so) -
perh
ydro
pyri
mid
ine
N-N
itros
o(2
22-
tri
uoro
ethy
l)et
hyla
min
e1-
Nitr
oso-
34
5-tr
imet
hylp
iper
azin
eN
-Nitr
osoa
llyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nit
roso
ally
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itro
soal
lyle
than
olam
ine
N-N
itros
obis
( 2-h
ydro
xypr
opyl
) am
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
dipr
opyl
amin
eN
itros
oeth
ylm
ethy
lam
ine
N-N
itros
omet
hyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nitr
osom
ethy
l-( 2
-hyd
roxy
ethy
l)am
ine
N-N
itro
som
ethy
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itros
omet
hyl(
2-ox
opro
pyl)
amin
eN
-Nit
roso
norn
icot
ine-
1-N
-oxi
de
N-N
itro
sopi
peri
dine
z P
hena
cetin
z Ph
enyl
glyc
idyl
ethe
r1
2-Pr
opyl
ene
oxid
ez V
inyl
acet
atez
Vin
ylch
lori
dez
Ner
vous
Mou
se3
13-
But
adie
nez
N-N
itros
odim
ethy
lam
inez
Pro
carb
azin
eH
Clz
syst
emR
at21
Acr
ylam
ide
Acr
ylon
itril
eB
rom
oeth
anez
Chl
oram
buci
lz 1-
( 4-C
hlor
ophe
nyl)
-1-p
heny
l-2-
prop
ynyl
carb
amat
eC
yclo
phos
pham
idez
1-E
thyl
-1-n
itros
oure
aE
thyl
eneo
xide
z 1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
eaG
lu-P
-1z
Glu
-P-2
z G
lyci
dolz
R(
) -2-
Met
hyl-
N-n
itro
sopi
peri
dine
S(
) -2-
Met
hyl-
N-n
itro
sopi
peri
dine
M
ethy
lnit
ram
ine
N-N
itros
o-N
-met
hylu
reaz
N-N
itros
odie
than
olam
ine
1-P
heny
l-3
3-di
met
hyltr
iaze
neP
roca
rbaz
ine
HC
lz P
ropa
nesu
ltone
Vin
ylch
lori
dez
Ora
lcav
ityc
Ham
ster
4A
ceta
ldeh
yde
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
N-N
itros
omor
phol
ine
N-N
itro
sopi
peri
dine
z
Mou
se3
N-N
itros
ohex
amet
hyle
neim
ine
12
3-T
rich
loro
prop
anez
Vin
ylac
etat
ez
Rat
32A
cryl
amid
eA
cryl
onitr
ile
Ben
zene
z 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
CI
dir
ectb
lue
15C
Id
irec
tblu
e21
8z C
hlor
opre
nez
3-D
iazo
tyra
min
eH
Cl
12-
Dib
rom
o-3-
chlo
ropr
opan
ez 3
3-D
imet
hoxy
benz
idin
e2H
Cl
33
-Dim
ethy
lben
zidi
ne2
HC
lz D
imet
hylv
inyl
chlo
ride
z D
initr
osoh
omop
iper
azin
eG
lyci
dolz
IQz
MeA
-a-C
acet
atez
N-N
itros
o-2
3-di
hydr
oxyp
ropy
l-2-
hydr
oxyp
ropy
lam
ine
Nit
roso
-23
-dih
ydro
xypr
opyl
-2-
oxop
ropy
lam
ine
Nitr
oso-
N-m
ethy
l-N
-(2-
phen
yl) e
thyl
amin
eN
itro
soam
ylur
etha
nN
-Nitr
osod
ieth
ylam
ine
Nit
roso
ethy
lure
than
N
itros
ohep
tam
ethy
lene
imin
e1-
Nitr
osoh
ydan
toin
N-N
itros
omet
hyl(
2-ox
opro
pyl)
amin
eN
-Nit
roso
thia
ldin
eN
-Nitr
osot
hiom
orph
olin
eC
Ia
cid
red
114
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tolu
eney
12
3-T
rich
loro
prop
anez
Xyl
ene
mix
ture
( m-x
ylen
eo-
xyle
nep
-xyl
ene)
Ova
ryM
ouse
10B
enze
nez
13-
But
adie
nez
Die
thyl
stil
best
rolz
N-M
ethy
lola
cryl
amid
ey 5-
Nitr
o-2-
fura
ldeh
yde
sem
icar
bazo
nez
5-N
itroa
cena
phth
enez
1-[(
5-N
itro
furf
uryl
iden
e)am
ino]
hyda
ntoi
nz P
heno
lpht
hale
inz
Tam
oxif
enci
trat
ez 4-
Vin
ylcy
cloh
exen
ePa
ncre
asH
amst
er3
Nitr
oso-
23-
dihy
drox
ypro
pyl-
2-ox
opro
pyla
min
eN
itro
so-2
6-d
imet
hylm
orph
olin
eN
itro
so-2
-oxo
prop
ylet
hano
lam
ine
Mon
key
1U
reth
anez
Rat
222-
Am
ino-
5-ni
trop
heno
ly 1-
( Am
inom
ethy
l)cy
cloh
exan
eace
ticac
idA
zase
rine
But
ylbe
nzyl
phth
alat
ey C
hlor
endi
cac
idz
Cin
nam
ylan
thra
nila
tez
Clo
bra
tey
Dic
hlor
vosz
Eth
ylal
coho
ly H
ydro
chlo
ro
uoro
carb
on12
3IQ
HC
lM
alon
alde
hyde
sod
ium
saltz
MeA
-a-C
acet
atez
2-M
erca
ptob
enzo
thia
zole
y M
ethy
lclo
fena
pate
z N
-(N
-Met
hyl-
N-n
itros
ocar
bam
oyl)
-l-o
rnit
hine
4-(
Met
hyln
itro
sam
ino)
-1-(
3-py
ridy
l)-1
-but
anol
4-(
Met
hyln
itros
amin
o)-1
-( 3
-pyr
idyl
) -1-
( but
anon
e)N
afen
opin
Nitr
ofen
z To
luen
edi
isoc
yana
tec
omm
erci
algr
ade
( 24
( 80
) -an
d2
6( 2
0) -
)z1
23
-Tri
chlo
ropr
opan
ez
Peri
tone
alM
ouse
8B
is-1
2-(
chlo
rom
etho
xy) e
than
eB
is-1
4-(
chlo
rom
etho
xy) -
p-xy
lene
Bis
-(ch
loro
met
hyl)
ethe
rz C
hlor
opre
nez
tran
s-1
4-D
ichl
orob
uten
e-2
cavi
tyD
imet
hylc
arba
myl
chlo
ride
Phe
noxy
benz
amin
eH
Clz
Tri
s-1
23-
( chl
orom
etho
xy) p
ropa
neR
at22
Acr
onyc
ine
Acr
ylam
ide
Act
inom
ycin
DA
nili
neH
Cly
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
rom
ate
pota
ssiu
mz
Chl
oroz
otoc
in
Cyt
embe
nay
Dap
sone
y 1
2-D
ibro
moe
than
ez D
ibro
mom
anni
tolz
33
-Dim
ethy
lben
zidi
ne2
HC
lz 1
4-D
ioxa
nez
Eth
ylen
eox
idez
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Gly
cido
lz M
elph
alan
z N
-Met
hyl-
N4
-din
itros
oani
line
Mit
omyc
in-C
N-N
itro
so-2
24
-tri
met
hyl-
12-
dihy
droq
uino
line
poly
mer
Ph
enox
yben
zam
ine
HC
lz o-
Tolu
idin
eH
Clz
( Con
tinue
don
next
page
)
645
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Pitu
itar
ygl
and
Mou
se8
Die
thyl
stil
best
rolz
Eno
vid
Eth
ylen
eth
iour
eaz
Iodi
nate
dgl
ycer
olz
Isop
rene
Nor
lest
rinz
Pro
pylt
hiou
raci
lz Z
eara
leno
ney
Rat
73-
Am
inot
riaz
olez
12-
Dib
rom
oeth
anez
Die
thyl
stil
best
rolz
Eth
ylal
coho
ly 2-
Mer
capt
oben
zoth
iazo
ley
Met
roni
dazo
lez
Nor
lest
rinz
Pros
tate
Rat
4C
adm
ium
chlo
ride
N-N
itros
obis
( 2-h
ydro
xypr
opyl
) am
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
PhIP
HC
lz
Skin
Ham
ster
2U
reth
anez
Vin
ylch
lori
dez
Mou
se5
5-A
zacy
tidin
ez 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Chl
orop
rene
z G
lyci
dolz
Thi
o-te
paz
Rat
332-
Ace
tyla
min
ouo
rene
z 3-
Am
ino-
9-et
hylc
arba
zole
mix
ture
z 1-
Azo
xypr
opan
e2-
Azo
xypr
opan
eB
enze
nez
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
ol
tech
nica
lgra
dez
CI
dir
ectb
lue
15C
arbo
xym
ethy
lnitr
osou
rea
24-
Dia
min
oani
sole
sulf
atez
Dib
rom
odul
cito
lz D
ibro
mom
anni
tolz
Dim
etho
xane
2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 3
3-D
imet
hoxy
benz
idin
e-4
4-d
iisoc
yana
tey
33
-Dim
etho
xybe
nzid
ine
2HC
l3
3-D
imet
hylb
enzi
dine
2H
Clz
Dim
ethy
lvin
ylch
lori
dez
24-
Din
itro
tolu
ene
( con
tain
ing
10-
15
26-
dini
trot
olue
ne)z
1-E
thyl
nitr
oso-
3-( 2
-hyd
roxy
ethy
l)-u
rea
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Gly
cido
lz 1-
( 2-H
ydro
xyet
hyl)
-nit
roso
-3-e
thyl
urea
IQ
z L
asio
carp
ine
MeI
Qxz
N-(
N-M
ethy
l-N
-nitr
osoc
arba
moy
l)-l
-orn
ithi
ne
5-N
itro-
o-an
isid
inez
CI
aci
dre
d11
4p-
Ros
anili
neH
Clz
Thi
o-te
paz
Thi
oure
ay V
inyl
chlo
ride
z F
Damp
Cvi
olet
no1
y
Smal
lint
esti
neM
ouse
6C
apta
folz
Cap
tanz
N-E
thyl
-N-n
itro
-N-n
itro
sogu
anid
ine
Hyd
roge
npe
roxi
deN
-Met
hyl-
N-n
itro-
N-n
itros
ogua
nidi
nez
N-(
Tri
chlo
rom
ethy
lthi
o)ph
thal
imid
eM
onke
y1
Ure
than
ez
Rat
29A
cryl
onitr
ile
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
is( 2
3-d
ibro
mop
ropy
l)ph
osph
ate
mag
nesi
umsa
lt4
-Bis
( 2-h
ydro
xyet
hyl)
amin
o-2-
( 5-n
itro
-2-t
hien
yl) q
uina
zolin
eC
Id
irec
tblu
e15
Car
boxy
met
hyln
itros
oure
a1-
( 4-C
hlor
ophe
nyl)
-1-p
heny
l-2-
prop
ynyl
carb
amat
e2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 3
3-D
imet
hoxy
benz
idin
e2H
Cl
46-
Dim
ethy
l-2-
( 5-n
itro
-2-f
uryl
)py
rim
idin
etr
ans-
2-[(
Dim
ethy
lam
ino)
met
hylim
ino]
-5-[
2-( 5
-nit
ro-2
-fur
yl) v
inyl
] -1
34-
oxad
iazo
le3
3-D
imet
hylb
enzi
dine
2H
Clz
Z-E
thyl
-ON
N-a
zoxy
met
hane
1-E
thyl
-1-n
itros
oure
aFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z G
lu-P
-1z
Glu
-P-2
z IQ
z L
asio
carp
ine
N-M
ethy
l-N
-nitr
o-N
-nitr
osog
uani
dine
z N
-[5-
( 5-N
itro-
2-fu
ryl)
-13
4-t
hiad
iazo
l-2-
yl] a
ceta
mid
ez N
-Nitr
oso-
N-i
sobu
tylu
rea
3-N
itro
so-2
-oxa
zoli
dino
neN
itro
soet
hylu
reth
ane
PhI
PH
Clz
Pro
pane
sulto
neQ
uerc
etin
y C
Ia
cid
red
114
Trp
-P-2
acet
atez
Sple
enR
at7
Ani
line
HC
ly A
zobe
nzen
ey p-
Chl
oroa
nili
neH
Clz
Dap
sone
y o-
Nitr
osot
olue
neD
ampC
red
no9
y o-
Tolu
idin
eH
Clz
Stom
ach
Ham
ster
18A
F-2z
14-
Din
itros
o-2
6-di
met
hylp
iper
azin
eFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z H
ydra
zine
z N
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
N-[
4-( 5
-Nitr
o-2-
fury
l)-2
-thi
azol
yl] a
ceta
mid
eN
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] for
mam
idez
N-N
itro
so-2
3-d
ihyd
roxy
prop
yl-2
-hyd
roxy
prop
ylam
ine
Nitr
oso-
23-
dihy
drox
ypro
pyl-
2-ox
opro
pyla
min
eN
-Nitr
oso-
ethy
l-2-
oxop
ropy
lure
aN
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aN
itros
o-5-
met
hylo
xazo
lidon
eN
-Nit
roso
-N-m
ethy
lure
than
N-N
itros
o-1
3-ox
azol
idin
eN
-Nit
roso
-2-p
heny
leth
ylur
ea1
-Nit
roso
-34
5-t
rim
ethy
lpip
eraz
ine
Ure
than
ez V
inyl
chlo
ride
z
Mou
se63
Ace
tald
ehyd
em
ethy
lfor
myl
hydr
azon
eA
ciu
orfe
nA
F-2
z 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 2-
Am
ino-
4-( 5
-nitr
o-2-
fury
l)th
iazo
lez
tran
s-5-
Am
ino-
3[2-
( 5-n
itro-
2-fu
ryl)
viny
l] -1
24-
oxad
iazo
leA
reco
line
HC
lB
enza
ldeh
ydey
Ben
zofu
ranz
Ben
zotr
ichl
orid
eB
enzy
lace
tate
y B
enzy
lchl
orid
ey B
rom
oeth
anol
13
-But
adie
nez
But
ylat
edhy
drox
yani
sole
z 1
1-di
-N-B
utyl
hydr
azin
eC
affe
icac
idz
Cap
tafo
lz C
arba
zole
Cat
echo
lz 3-
Chl
oro-
2-m
ethy
lpro
pene
tec
hnic
algr
ade
( con
tain
ing
5di
met
hylv
inyl
chlo
ride
)z3
-(C
hlor
omet
hyl)
pyri
dine
HC
lz C
hlor
opre
nez
2-C
hlor
opro
pana
l1-
Chl
orop
rope
neC
ypro
tero
neac
etat
e1
1-D
ially
lhyd
razi
ne1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dic
hlor
vosz
Dig
lyci
dylr
esor
cino
leth
ert
echn
ical
grad
ez D
imet
hylv
inyl
chlo
ride
z D
init
roso
pipe
razi
neE
stra
diol
mus
tard
y E
thyl
acry
late
z Fo
rmic
acid
2-[ 4
-( 5
-nit
ro-2
-fur
yl) -
2-th
iazo
lyl] h
ydra
zide
z G
lyci
dolz
2-H
ydra
zino
-4-(
5-ni
tro-
2-fu
ryl)
thia
zole
z N
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
ICI
1628
46z
IQz
Isop
rene
Lov
asta
tin
MeI
Q1
-Met
hyl-
14-
dihy
dro-
7-[ 2
-(5-
nitr
ofur
yl) v
inyl
] -4-
oxo-
18-
naph
thyr
idin
e-3-
carb
oxyl
ate
pota
ssiu
m3
-(5-
Nitr
o-2-
fury
l)-
imid
azo(
12-
a) p
yrid
inez
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
N-[
4-( 5
-Nitr
o-2-
fury
l)-2
-thi
azol
yl] f
orm
amid
ez N
-Nit
roso
-N
-met
hylu
reaz
Nit
roso
dibu
tyla
min
ez N
-Nit
roso
hexa
met
hyle
neim
ine
N-N
itros
opip
erid
inez
b-P
ropi
olac
tone
z Se
sam
olz
Sty
rene
oxid
ez Te
lone
IIt
echn
ical
grad
ez N
-(T
rich
loro
met
hylth
io) p
htha
limid
e1
23-
Tri
chlo
ropr
opan
ez 2
22-
Tri
uo
ro-N
-[4-
( 5-n
itro
-2-f
uryl
) -2-
thia
zoly
l]ac
etam
idez
Tri
ur
alin
tec
hnic
algr
adey
Tri
s(2-
chlo
roet
hyl)
phos
phat
ez T
ris(
23-
dibr
omop
ropy
l)ph
osph
atez
Vin
ylac
etat
ez
Rat
85A
ceto
ne[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zone
1-A
ceto
xysa
frol
ey A
cryl
onitr
ile
1-A
llyl
-1-n
itro
sour
ea2
-Am
ino-
5-( 5
-nit
ro-2
-fur
yl) -
13
4-ox
adia
zole
2-
Am
ino-
5-( 5
-nitr
o-2-
fury
l)-1
34
-thi
adia
zole
2-A
min
o-4-
( 5-n
itro
-2-f
uryl
) thi
azol
ez 1-
Am
yl-1
-nit
roso
urea
Ari
stol
ochi
cac
id
sodi
umsa
lt( 7
7A
AI
21
AA
II)
Ben
zene
z B
enzo
( a) p
yren
ez 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bis
( 23
-dib
rom
opro
pyl)
phos
phat
em
agne
sium
salt
BL
-634
1H
Cl
N-n
-But
yl-N
-nitr
osou
rea
But
ylat
edhy
drox
yani
sole
z b
-But
yrol
acto
neC
affe
icac
idz
Cat
echo
lz 3-
Chl
oro-
2-m
ethy
lpro
pene
tec
hnic
algr
ade
( con
tain
ing
5di
met
hylv
inyl
chlo
ride
)z4
-Chl
oro-
o-ph
enyl
ened
iam
inez
Chl
oro
uoro
met
hane
3-
( Chl
orom
ethy
l)py
ridi
neH
Clz
Cip
rob
rate
z C
upfe
rron
z 1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
Dig
lyci
dylr
esor
cino
leth
ert
echn
ical
grad
ez 2
5-D
imet
hoxy
-4-a
min
osti
lben
ez D
imet
hylh
ydro
gen
phos
phit
ey 4
6-D
imet
hyl-
2-( 5
-nit
ro-2
-fu
ryl)
pyri
mid
ine
tran
s-2-
[(D
imet
hyla
min
o)m
ethy
limin
o]-5
-[2-
( 5-n
itro
-2-f
uryl
) vin
yl] -
13
4-ox
adia
zole
Dim
ethy
lvin
ylch
lori
dez
Epi
chlo
rohy
drin
y E
thyl
acry
late
z E
thyl
ene
oxid
ez 2-
Flu
oroe
thyl
-nitr
osou
rea
Gly
cido
lz N
-Hex
ylni
tros
oure
a1-
Hyd
roxy
anth
raqu
inon
e1-
( 2-H
ydro
xyet
hyl)
-1-
nitr
osou
reaz
1-( 3
-Hyd
roxy
prop
yl) -
1-ni
tros
oure
a1
-Hyd
roxy
safr
olez
ICI
1628
46z
Lox
tidin
eL
upit
idin
e3H
Cl
Mer
curi
cch
lori
dey
3-M
etho
xyca
tech
ol4
-Met
hoxy
phen
olN
-Met
hyl-
N-n
itro-
N-n
itros
ogua
nidi
nez
N-M
ethy
l-N
-nit
roso
benz
amid
e4-
Met
hylc
atec
hol
Met
hyln
itro
socy
anam
ide
3-( 5
-Nit
ro-2
-fur
yl) -
imid
azo(
12-
a) p
yrid
inez
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
4-( 5
-Nit
ro-2
-fur
yl) t
hiaz
ole
2-N
itro
uo
rene
8-N
itro
quin
olin
eN
itro
so-B
aygo
nN
-Nit
roso
-23
-dih
ydro
xypr
opyl
-2-h
ydro
xypr
opyl
amin
eN
itros
o-2
3-di
hydr
oxyp
ropy
l-2-
oxop
ropy
lam
ine
1-N
itro
so-3
5-d
imet
hyl-
4-be
nzoy
lpip
eraz
ine
N-N
itro
so-N
-met
hyl-
N-d
odec
ylam
ine
Nitr
oso-
N-m
ethy
l-N
-(2-
phen
yl) e
thyl
amin
eN
-Nit
roso
-N-m
ethy
ldec
ylam
ine
N-N
itro
so-N
-met
hylu
reaz
Nit
roso
-12
36
-tet
rahy
drop
yrid
ine
N-N
itro
sobe
nzth
iazu
ron
Nitr
osod
ibut
ylam
inez
N-N
itros
odie
thyl
amin
eN
-Nit
roso
ephe
drin
eN
itros
oeth
ylur
etha
nO
mep
razo
ley
Phen
acet
inz
Piv
alol
acto
ney
b-P
ropi
olac
tone
z N
-Pro
pyl-
N-n
itro
-N-n
itro
sogu
anid
ine
12-
Pro
pyle
neox
idez
Ses
amol
z St
yren
eox
idez
Sulf
alla
tez
Telo
neII
tec
hnic
algr
adez
12
3-T
rich
loro
prop
anez
24
6-T
rim
ethy
lani
line
HC
lz
646
Subc
utan
eous
Mou
se4
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 1
2-D
ibro
moe
than
ez N
2-c
-Glu
tam
yl-p
-hyd
razi
nobe
nzoi
cac
idG
lyci
dolz
tissu
eR
at13
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 2
4-D
iam
inot
olue
ne2
HC
lz 1
2-D
ichl
oroe
than
ez D
imet
hoxa
ne1
4-D
ioxa
nez
MeA
-a-C
acet
atez
44
-Met
hyle
ne-b
is( 2
-met
hyla
nili
ne)
o-N
itro
soto
luen
ep-
Ros
anili
neH
Clz
Tolu
ene
diis
ocya
nate
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
o-T
olui
dine
HC
lz 2
45-
Tri
met
hyla
nilin
eH
Clz
25-
Xyl
idin
eH
Clz
Test
isM
ouse
4D
ieth
ylst
ilbe
stro
lz Fi
nast
erid
eR
eser
pine
z Ta
mox
ifen
citr
atez
Rat
185-
Aza
cytid
inez
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 1
3-B
utad
iene
z N
-But
yl-N
-(4-
hydr
oxyb
utyl
) nitr
osam
ine
Cad
miu
mch
lori
de
2-C
hlor
o-1
11-
tri
uoro
etha
ne1
1-D
ichl
oro-
1-u
oroe
than
eH
ydro
chlo
rou
oroc
arbo
n12
3M
ethy
lter
t-bu
tyle
ther
z M
ethy
lclo
fena
pate
z M
etro
nida
zole
z N
-Nit
roso
dim
ethy
lam
inez
Oxo
linic
acid
y SD
Z20
0-11
01
11
2-Te
tra
uoro
etha
ney
Tri
chlo
roet
hyle
nez
Tri
nitr
ogly
ceri
nV
inyl
chlo
ride
z
Thy
roid
glan
dH
amst
er4
Hex
achl
orob
enze
nez
Hyd
razi
nez
Met
hylt
hiou
raci
lU
reth
anez
Mou
se18
3-A
min
o-4-
etho
xyac
etan
ilide
y H
Cbl
ueno
1z
tert
-But
ylal
coho
lz C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
24
-Dia
min
oani
sole
sulf
atez
Die
thyl
stil
best
rolz
Dox
ylam
ine
succ
inat
ez E
thio
nam
idey
Eth
ylen
eth
iour
eaz
44
-Met
hyle
nedi
anil
ine
2HC
lz 1
5-N
apht
hale
nedi
amin
ez N
itrob
enze
nez
Oxa
zepa
my
44
-Oxy
dian
iline
z C
Ip
igm
entr
ed3z
Sulf
amet
hazi
ne2
37
8-T
etra
chlo
rodi
benz
o-p-
diox
inz
44
-Thi
odia
nilin
ez
Rat
33A
cryl
amid
e3-
Am
inot
riaz
olez
o-A
nisi
dine
HC
lz B
emit
radi
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bro
mat
epo
tass
ium
z C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
Chl
orop
rene
z 2
4-D
iam
inoa
niso
lesu
lfat
ez N
N-D
ieth
ylth
iour
eay
1-E
thyl
-1-n
itro
sour
ea
Eth
ylen
eth
iour
eaz
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Flu
vast
atin
Gly
cido
lz Io
dina
ted
glyc
erol
z Is
obut
eney
Mal
onal
dehy
des
odiu
msa
ltz
Met
him
azol
e4
4-M
ethy
lene
bis(
NN
-dim
ethy
l)be
nzen
amin
ez 4
4-M
ethy
lene
dian
iline
2H
Clz
Mir
exp
hoto
-N
itro
benz
enez
N-N
itro
sobi
s(2-
oxop
ropy
l)am
ine
44
-Oxy
dian
iline
z Pr
opyl
thio
urac
ilz p-
Ros
anil
ine
HC
lz 2
37
8-Te
trac
hlor
odib
enzo
-p-d
ioxi
nz 4
4-T
hiod
iani
linez
Thi
oura
cilz
Tri
met
hylt
hiou
reay
Vin
ylac
etat
ez Z
inc
dim
ethy
ldith
ioca
rbam
atez
Uri
nary
blad
der
Dog
23
3-D
ichl
orob
enzi
dine
44
-Met
hyle
ne-b
is( 2
-chl
oroa
nilin
e)H
amst
er3
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-t
hiaz
olyl
] hyd
razi
dez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
acet
amid
eN
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] for
mam
idez
Mou
se12
2-A
cety
lam
ino
uore
nez
4-A
min
odip
heny
l2-
Am
inod
iphe
nyle
neox
ide
o-A
nisi
dine
HC
lz 4-
Chl
oro-
4-a
min
odip
heny
leth
erz
p-C
resi
dine
z 4-
Eth
ylsu
lpho
nyln
apht
hale
ne-1
-sul
fona
mid
eN
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez P
hena
cetin
z Te
lone
IIt
echn
ical
grad
ez U
raci
lz
Mon
key
12-
Nap
hthy
lam
inez
Rat
49A
ceta
min
ophe
nz A
llyli
soth
iocy
anat
ey 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 2-
Am
ino-
4-( 5
-nitr
o-2-
fury
l)th
iazo
lez
4-A
min
o-2-
nitr
ophe
noly
11-A
min
ound
ecan
oic
acid
y o-
Ani
sidi
neH
Clz
Ari
stol
ochi
cac
ids
odiu
msa
lt( 7
7A
AI
21
AA
II)
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez C
Id
ispe
rse
blue
1y N
-But
yl-N
-(4-
hydr
oxyb
utyl
) nitr
osam
ine
4-C
hlor
o-o-
phen
ylen
edia
min
ez m
-Cre
sidi
ney
p-C
resi
dine
z C
yclo
phos
pham
idez
Die
thyl
ene
glyc
olD
imet
hyla
rsin
icac
idy
Fose
tylA
lIQ
HC
lM
eA-a
-Cac
etat
ez M
elam
iney
2-M
etho
xy-3
-am
inod
iben
zofu
ran
2-N
apht
hyla
min
ez N
itril
otri
acet
icac
idz
Nitr
ilot
riac
etic
acid
tri
sodi
umsa
ltm
onoh
ydra
tey
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez o-
Nitr
oani
sole
z N
-Nitr
oso-
N-m
ethy
l-N
-dod
ecyl
amin
eN
-Nitr
oso-
N-m
ethy
l-N
-tet
rade
cyla
min
eN
-Nit
roso
-N-m
ethy
ldec
ylam
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
Nitr
osod
ibut
ylam
inez
N-N
itro
sodi
phen
ylam
iney
o-N
itros
otol
uene
N-O
xydi
ethy
lene
thio
carb
amyl
-N-o
xydi
ethy
lene
sulf
enam
ide
Phe
nace
tinz
Phen
azon
eo-
Phen
ylph
enat
eso
dium
y o-
Phen
ylph
enol
y P
otas
sium
bica
rbon
ate
Purp
urin
Que
rcet
iny
p-Q
uino
nedi
oxim
ey Sa
ccha
rin
sodi
umy
Sali
cyla
zosu
lfap
yrid
inez
o-To
luen
esul
fona
mid
eo-
Tolu
idin
eH
Clz
Trp
-P-2
acet
atez
Ura
cilz
Ute
rus
Ham
ster
1N
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aM
ouse
12B
rom
oeth
anez
Chl
oroe
than
ey D
acar
bazi
nez
12-
Dic
hlor
oeth
anez
Die
thyl
stil
best
rolz
Eth
ylen
eox
idez
Gly
cido
lz ( N
-6) -
( Met
hyln
itros
o)ad
enos
ine
Proc
arba
zine
HC
lz 1
23-
Tri
chlo
ropr
opan
ez T
rim
ethy
lpho
spha
tey
Vin
ylac
etat
ez
Rat
26A
cryl
amid
e1-
Ally
l-1-
nitr
osou
rea
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
1-A
myl
-1-n
itros
oure
aA
traz
iney
CI
dir
ectb
lue
15B
rom
ocri
ptin
em
esyl
atey
N-n
-But
yl-N
-nit
roso
urea
Cal
cium
valp
roat
eC
apta
nz 2-
Chl
oro-
11
1-tr
iuo
roet
hane
Dac
arba
zine
z D
amin
ozid
ez 3
3-D
imet
hoxy
benz
idin
e-4
4-d
iisoc
yana
tey
33
-Dim
etho
xybe
nzid
ine
2HC
lD
imet
hyla
min
oeth
ylni
tros
oeth
ylur
ean
itri
tesa
lt1-
Eth
ylni
tros
o-3-
( 2-h
ydro
xyet
hyl)
-ure
a1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
N-H
exyl
nitr
osou
rea
ICR
F-1
59z
Isop
hosp
ham
idez
15-
Nap
htha
lene
diam
inez
Nit
robe
nzen
ez N
orle
stri
nz 4
4-T
hiod
iani
linez
Vin
ylac
etat
ez
Vag
ina
Mou
se1
AZ
Tz
Rat
2A
ZT
z N
-n-B
utyl
-N-n
itro
sour
ea( C
ontin
ued
onne
xtpa
ge)
647
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Vas
cula
rsy
stem
Ham
ster
91
2-D
imet
hylh
ydra
zine
2H
Cl
Gly
cido
lz H
exac
hlor
oben
zene
z N
-Nit
roso
-eth
yl-2
-oxo
prop
ylur
eaN
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aN
-Nitr
oso-
oxop
ropy
lchl
oroe
thyl
urea
N-N
itro
so-o
xopr
opyl
urea
N-N
itros
o-2-
phen
ylet
hylu
rea
Vin
ylch
lori
dez
Mou
se59
A-a
-CN
-Ace
tyl-
4-( h
ydro
xym
ethy
l)ph
enyl
hydr
azin
e1-
Ace
tyl-
2-ph
enyl
hydr
azin
eA
llyl
hydr
azin
eH
Cl
Are
colin
eH
Cl
Aza
thio
prin
eB
enzi
dine
2H
Cl
2-B
iphe
nyla
min
eH
Cly
13-
But
adie
nez
Cap
tafo
lz C
arba
myl
hydr
azin
eH
Cl
4-C
hlor
o-4
-am
inod
iphe
nyle
ther
z 1-
Chl
oro-
4-ni
trob
enze
ney
5-C
hlor
o-o-
tolu
idin
ey 4-
Chl
oro-
o-to
luid
ine
HC
ly p-
Chl
oroa
nilin
eH
Clz
Chl
orop
rene
z C
upfe
rron
z D
acar
bazi
nez
Dam
inoz
idez
24-
Dia
min
otol
uene
2H
Clz
12-
Dib
rom
oeth
anez
Dif
talo
ne7
12-
Dim
ethy
lben
z(a)
anth
race
ne1
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
N-E
thyl
-N-f
orm
ylhy
draz
ine
Eth
ylhy
draz
ine
HC
lG
lu-P
-1z
Glu
-P-2
z p-
Hyd
razi
nobe
nzoi
cac
idH
Cl
1-H
ydro
xysa
frol
ez Is
opre
neM
eA-a
-Cac
etat
ez N
-Met
hyl-
N-f
orm
ylhy
draz
ine
2-M
ethy
l-1-
nitr
oant
hraq
uino
nez
Mic
hler
rsquoske
tone
z 5-
Nitr
o-o-
tolu
idin
ey N
itro
fenz
N-N
itros
o-N
-met
hylu
reaz
Pent
achl
oroa
niso
lez
23
45
6-Pe
ntac
hlor
ophe
nol(
Dow
icid
eE
C-7
)y2
34
56
-Pen
tach
loro
phen
olt
echn
ical
grad
ez n-
Pen
tylh
ydra
zine
HC
lPh
enyl
ethy
lhyd
razi
nesu
lfat
ePh
enyl
hydr
azin
eH
Cl
Ster
igm
atoc
ysti
nz Te
tra
uoro
ethy
lene
z To
luen
edi
isoc
yana
tec
omm
erci
algr
ade
( 24
( 80
) -an
d2
6( 2
0) -
)zo
-Tol
uidi
neH
Clz
24
6-T
rich
loro
anil
iney
24
5-T
rim
ethy
lani
line
HC
lz 2
46-
Tri
met
hyla
nili
neH
Clz
Ure
than
ez V
inyl
carb
amat
eV
inyl
chlo
ride
z V
inyl
uor
idez
Vin
ylid
ene
chlo
ride
y 2
5-X
ylid
ine
HC
lz
Mon
key
2A
ato
xin
B1y
Ure
than
ez
Rat
32A
nilin
eH
Cly
Azo
benz
eney
Ben
zene
z C
livor
ine
Cup
ferr
onz
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
Z-E
thyl
-ON
N-a
zoxy
etha
neZ
-Eth
yl-O
NN
-azo
xym
etha
neI
QH
Cl
Las
ioca
rpin
e4
4-M
ethy
lene
-bis
( 2-c
hlor
oani
line)
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
N-N
itros
o-( 2
-hyd
roxy
prop
yl) -
( 2-h
ydro
xyet
hyl)
amin
eN
itro
so-1
23
6-t
etra
hydr
opyr
idin
eN
-Nitr
osob
is( 2
-oxo
prop
yl) a
min
eN
-Nit
roso
diet
hano
lam
ine
N-N
itro
sodi
ethy
lam
ine
N-N
itros
odim
ethy
lam
inez
N-N
itros
omet
hyl-
( 2-t
osyl
oxye
thyl
) am
ine
N-N
itros
omor
phol
ine
N-N
itro
sopy
rrol
idin
ez Pe
tasi
teni
neS
teri
gmat
ocys
tinz
Sym
phyt
ine
Tetr
auo
roet
hyle
nez
o-To
luid
ine
HC
lz T
rp-P
-2ac
etat
ez V
inyl
brom
ide
Vin
ylch
lori
dez
Vin
yl
uori
dez
aT
here
was
nore
port
edta
rget
site
in1
spec
ies
( rat
sor
mic
e)fo
r5
chem
ical
sw
ithsu
pers
crip
tsb
utth
ech
emic
alw
asev
alua
ted
byth
epu
blis
hed
auth
oras
aca
rcin
ogen
ald
rinz
diel
drin
z N
-nit
roso
pyrr
olid
inez
23
45
6-pe
ntac
hlor
ophe
nol
( Dow
icid
eE
C-7
)ya
ndur
etha
nez
bN
asal
cavi
tyin
clud
estis
sues
ofth
eno
sen
asal
turb
inat
esp
aran
asal
sinu
ses
and
trac
hea
c Ora
lcav
ityin
clud
estis
sues
ofth
em
outh
oro
phar
ynx
phar
ynx
and
lary
nx
Ach
emic
alis
liste
dun
der
each
orga
nev
alua
ted
aspo
sitiv
ein
anex
peri
men
tin
that
spec
ies
byat
leas
t1au
thor
The
refo
rea
chem
ical
may
beli
sted
unde
rse
vera
ltar
geto
rgan
san
dev
ery
chem
ical
liste
din
the
tabl
eis
posi
tive
inat
leas
t1sp
ecie
sIn
orde
rto
com
pare
resu
ltsin
rats
and
mic
esy
mbo
lsfo
llow
chem
ical
ste
sted
inbo
thsp
ecie
sa
zin
dica
tes
that
the
chem
ical
ispo
sitiv
eat
som
esi
tein
both
spec
ies
and
ay
indi
cate
sth
atit
was
test
edin
both
butp
ositi
vein
only
1a
Nth
enu
mbe
rof
chem
ical
sw
ithat
leas
t1po
sitiv
ete
stat
that
site
inth
atsp
ecie
sB
ecau
sem
any
chem
ical
sin
duce
tum
ors
atm
ore
than
1si
tein
agi
ven
spec
ies
man
ych
emic
als
appe
arm
ore
than
once
inth
eta
ble
648
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649
species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters
RESULTS IN RATS AND MICE
For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens
TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database
Chemicals evaluated as carcinogenic in
Rats Mice
All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)
Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2
a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not
b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats
All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical
to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included
The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site
Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common
650 GOLD ET AL TOXICOLOGIC PATHOLOGY
TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)
Target site Agent mixture or industrial process
Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e
Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke
Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products
Brain Vinyl chloride a
Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e
Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena
Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system
Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as
a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell
lymphotropic virus type I (HTLV-I) Vinyl chloridea
Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production
Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)
Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea
Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea
Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)
Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea
Mesenchymal tumors Azathioprinea
Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust
Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust
Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid
(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke
Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production
8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots
Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e
Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays
IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD
IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no
tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance
is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651
sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites
Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to
be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)
Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)
Target Organs of Human CarcinogensTo complement the compendium of target organs in car-
cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke
In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)
Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens
Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from
bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)
ACKNOWLEDGMENTS
We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention
REFERENCES
1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56
2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600
3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998
4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685
5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404
6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605
7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246
8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100
9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash
23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC
11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the
652 GOLD ET AL TOXICOLOGIC PATHOLOGY
US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240
12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute
13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program
14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX
15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11
16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash
34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c
Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729
Rat
102
4-A
cety
lam
inob
iphe
nyl
2-A
cety
lam
ino
uore
nez
Acr
onyc
ine
Acr
ylam
ide
Acr
ylon
itri
leA
F-2
z 1-
Ally
l-1-
nitr
osou
rea
2-A
min
o-5-
( 5-n
itro-
2-fu
ryl)
-13
4-
oxad
iazo
le2
-Am
ino-
5-( 5
-nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
e2-
Am
ino-
5-ni
trot
hiaz
oley
4-A
min
odip
heny
lHC
l1-
Am
yl-1
-nit
roso
urea
Atr
azin
ey B
emit
radi
ne
Ben
zidi
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
4-B
is( 2
-hyd
roxy
ethy
l)am
ino-
2-( 5
-nit
ro-2
-thi
enyl
) qui
nazo
line
13-
But
adie
nez
N-n
-But
yl-N
-nitr
osou
rea
Cap
tafo
lz C
arbo
nte
trac
hlor
idez
Car
boxy
met
hyln
itros
oure
aC
hlor
ambu
cilz
Chl
orop
rene
z C
ytem
bena
y D
acar
bazi
nez
N-1
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ceta
mid
ouo
rene
46
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min
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( 5-n
itro-
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z 1
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prop
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Dib
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anez
Dib
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oman
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lz 1
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33
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oben
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ichl
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than
ez 3
3-D
imet
hoxy
benz
idin
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Cl
46-
Dim
ethy
l-2-
( 5-n
itro-
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ryl)
pyri
mid
ine
12-
Dim
ethy
l-5-
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ole
tran
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[(D
imet
hyla
min
o)m
ethy
limin
o]-5
-[2-
( 5-n
itro
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uryl
) vin
yl] -
13
4-ox
adia
zole
Dim
ethy
lam
inoe
thyl
nitr
osoe
thyl
urea
nitr
ite
salt
33
-Dim
ethy
lben
zidi
ne2
HC
lz 2-
( 22
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ethy
lhyd
razi
no) -
4-( 5
-nitr
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fury
l)th
iazo
le
24-
Din
itro
tolu
ene
( con
tain
ing
10-
15
24-
Dio
xane
z 1-
Eth
ylni
tros
o-3-
( 2-h
ydro
xyet
hyl)
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Eth
ylni
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xopr
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ea
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22
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uo
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Form
icac
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ethy
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ide
Form
icac
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[ 4-(
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tro-
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thia
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l] hyd
razi
dez
Gly
cido
lz H
exam
ethy
lmel
amin
eN
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ylni
tros
oure
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Hyd
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amin
ophe
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z 2-
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razi
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ro-2
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yl) t
hiaz
olez
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ydra
zino
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p-ni
trop
heny
l)th
iazo
lez
Hyd
razo
benz
enez
1-( 2
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roxy
ethy
l)-3
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rofu
rfur
ylid
ene)
amin
o]-2
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idaz
olid
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( 2-H
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itros
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az In
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etha
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IQz
IQH
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Ison
iazi
dz 2-
Met
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min
odib
enzo
fura
n4-
Met
hyl-
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5-ni
trof
urfu
rylid
ene)
amin
o]-2
-im
idaz
olid
inon
eN
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-Met
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N-n
itro
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oyl)
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rnit
hine
3-M
ethy
lcho
lant
hren
e4
4-M
ethy
lene
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s(2-
chlo
roan
iline
) 4
4-M
ethy
lene
-bis
( 2-m
ethy
lani
line)
Met
hyle
nech
lori
dez
Met
roni
dazo
lez
l-5-
Mor
phol
inom
ethy
l-3-
[(5-
nitr
ofur
fury
lide
ne) a
min
o]-
2-ox
azol
idin
one
HC
lN
ithia
zide
z 5-
Nitr
o-2-
fura
ldeh
yde
sem
icar
bazo
nez
3-( 5
-Nitr
o-2-
fury
l)-i
mid
azo(
12-
a)
pyri
dine
z 4-
( 5-N
itro-
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ryl)
thia
zole
N
-[4-
( 5-N
itro-
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ryl)
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hiaz
olyl
] ace
tam
ide
NN
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( 5-N
itro
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uryl
) -S-
tria
zine
-24
-diy
l] bis
acet
amid
e5-
Nitr
oace
naph
then
ez 1-
[(5-
Nit
rofu
rfur
ylid
ene)
amin
o]-2
-im
idaz
olid
inon
eN
itrom
etha
nez
1-N
itrop
yren
eN
orle
stri
nz O
chra
toxi
nA
z N
-(9-
Oxo
-2-
uore
nyl)
acet
amid
ePh
enac
etin
z Ph
enes
teri
nz Ph
IPH
Clz
Proc
arba
zine
HC
lz Pr
opan
esu
lton
e1
2-Pr
opyl
ene
oxid
ez St
yren
ey Su
lfal
late
z 4
4-S
ulfo
nylb
isac
etan
ilid
eTo
luen
edi
isoc
yana
te
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
o-T
olui
dine
HC
lz 1
23-
Tri
chlo
ropr
opan
ez 2
22-
Tri
uor
o-N
-[4-
( 5-n
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] ace
tam
idez
Trp
-P-2
acet
atez
Vin
ylch
lori
dez
FD
ampC
viol
etno
1y
Mes
ovar
ium
Rat
2Sa
lbut
amol
Ter
buta
line
Myo
card
ium
Mou
se2
Est
radi
olm
usta
rdy
Phen
este
rinz
Nas
alca
vity
bB
ush
baby
1N
-Nitr
osod
ieth
ylam
ine
Ham
ster
11A
ceta
ldeh
yde
Dia
llyln
itros
amin
eD
imet
hylc
arba
myl
chlo
ride
Hyd
razi
nez
Met
hyln
itro
sam
ino-
NN
-dim
ethy
leth
ylam
ine
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
N-N
itro
soal
lyl-
2-ox
opro
pyla
min
eN
-Nitr
osom
ethy
l-2
3-di
hydr
oxyp
ropy
lam
ine
N-N
itros
omor
phol
ine
N-N
itros
onor
nico
tine
N-N
itros
opip
erid
inez
Mou
se6
Ally
lgly
cidy
leth
ery
12-
Dib
rom
o-3-
chlo
ropr
opan
ez 1
2-D
ibro
moe
than
ez Fo
rmal
dehy
dez
N-N
itro
sohe
xam
ethy
lene
imin
e1
2-Pr
opyl
ene
oxid
ez
Rat
43A
ceta
ldeh
yde
Acr
ylon
itril
e1-
Azo
xypr
opan
eB
enze
nez
Bis
-(ch
loro
met
hyl)
ethe
rz p-
Cre
sidi
nez
Dia
llyln
itros
amin
e1
2-D
ibro
mo-
3-ch
loro
prop
anez
12-
Dib
rom
oeth
anez
Dim
ethy
lnitr
amin
eD
imet
hylv
inyl
chlo
ride
z D
initr
osoh
omop
iper
azin
e1
4-D
ioxa
nez
12-
Epo
xybu
tane
y Z
-Eth
yl-O
NN
-azo
xyet
hane
E
thyl
benz
ene
Eth
ylni
tros
ocya
nam
ide
Form
alde
hyde
z H
exam
ethy
lpho
spho
ram
ide
Hyd
razi
nez
N-N
itro
so-N
-met
hyld
ecyl
amin
edi
( N-N
itro
so) -
perh
ydro
pyri
mid
ine
N-N
itros
o(2
22-
tri
uoro
ethy
l)et
hyla
min
e1-
Nitr
oso-
34
5-tr
imet
hylp
iper
azin
eN
-Nitr
osoa
llyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nit
roso
ally
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itro
soal
lyle
than
olam
ine
N-N
itros
obis
( 2-h
ydro
xypr
opyl
) am
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
N-N
itro
sodi
etha
nola
min
eN
-Nit
roso
dipr
opyl
amin
eN
itros
oeth
ylm
ethy
lam
ine
N-N
itros
omet
hyl-
23-
dihy
drox
ypro
pyla
min
eN
-Nitr
osom
ethy
l-( 2
-hyd
roxy
ethy
l)am
ine
N-N
itro
som
ethy
l-2-
hydr
oxyp
ropy
lam
ine
N-N
itros
omet
hyl(
2-ox
opro
pyl)
amin
eN
-Nit
roso
norn
icot
ine-
1-N
-oxi
de
N-N
itro
sopi
peri
dine
z P
hena
cetin
z Ph
enyl
glyc
idyl
ethe
r1
2-Pr
opyl
ene
oxid
ez V
inyl
acet
atez
Vin
ylch
lori
dez
Ner
vous
Mou
se3
13-
But
adie
nez
N-N
itros
odim
ethy
lam
inez
Pro
carb
azin
eH
Clz
syst
emR
at21
Acr
ylam
ide
Acr
ylon
itril
eB
rom
oeth
anez
Chl
oram
buci
lz 1-
( 4-C
hlor
ophe
nyl)
-1-p
heny
l-2-
prop
ynyl
carb
amat
eC
yclo
phos
pham
idez
1-E
thyl
-1-n
itros
oure
aE
thyl
eneo
xide
z 1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
eaG
lu-P
-1z
Glu
-P-2
z G
lyci
dolz
R(
) -2-
Met
hyl-
N-n
itro
sopi
peri
dine
S(
) -2-
Met
hyl-
N-n
itro
sopi
peri
dine
M
ethy
lnit
ram
ine
N-N
itros
o-N
-met
hylu
reaz
N-N
itros
odie
than
olam
ine
1-P
heny
l-3
3-di
met
hyltr
iaze
neP
roca
rbaz
ine
HC
lz P
ropa
nesu
ltone
Vin
ylch
lori
dez
Ora
lcav
ityc
Ham
ster
4A
ceta
ldeh
yde
Nitr
oso-
26-
dim
ethy
lmor
phol
ine
N-N
itros
omor
phol
ine
N-N
itro
sopi
peri
dine
z
Mou
se3
N-N
itros
ohex
amet
hyle
neim
ine
12
3-T
rich
loro
prop
anez
Vin
ylac
etat
ez
Rat
32A
cryl
amid
eA
cryl
onitr
ile
Ben
zene
z 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
CI
dir
ectb
lue
15C
Id
irec
tblu
e21
8z C
hlor
opre
nez
3-D
iazo
tyra
min
eH
Cl
12-
Dib
rom
o-3-
chlo
ropr
opan
ez 3
3-D
imet
hoxy
benz
idin
e2H
Cl
33
-Dim
ethy
lben
zidi
ne2
HC
lz D
imet
hylv
inyl
chlo
ride
z D
initr
osoh
omop
iper
azin
eG
lyci
dolz
IQz
MeA
-a-C
acet
atez
N-N
itros
o-2
3-di
hydr
oxyp
ropy
l-2-
hydr
oxyp
ropy
lam
ine
Nit
roso
-23
-dih
ydro
xypr
opyl
-2-
oxop
ropy
lam
ine
Nitr
oso-
N-m
ethy
l-N
-(2-
phen
yl) e
thyl
amin
eN
itro
soam
ylur
etha
nN
-Nitr
osod
ieth
ylam
ine
Nit
roso
ethy
lure
than
N
itros
ohep
tam
ethy
lene
imin
e1-
Nitr
osoh
ydan
toin
N-N
itros
omet
hyl(
2-ox
opro
pyl)
amin
eN
-Nit
roso
thia
ldin
eN
-Nitr
osot
hiom
orph
olin
eC
Ia
cid
red
114
23
78-
Tetr
achl
orod
iben
zo-p
-dio
xinz
Tolu
eney
12
3-T
rich
loro
prop
anez
Xyl
ene
mix
ture
( m-x
ylen
eo-
xyle
nep
-xyl
ene)
Ova
ryM
ouse
10B
enze
nez
13-
But
adie
nez
Die
thyl
stil
best
rolz
N-M
ethy
lola
cryl
amid
ey 5-
Nitr
o-2-
fura
ldeh
yde
sem
icar
bazo
nez
5-N
itroa
cena
phth
enez
1-[(
5-N
itro
furf
uryl
iden
e)am
ino]
hyda
ntoi
nz P
heno
lpht
hale
inz
Tam
oxif
enci
trat
ez 4-
Vin
ylcy
cloh
exen
ePa
ncre
asH
amst
er3
Nitr
oso-
23-
dihy
drox
ypro
pyl-
2-ox
opro
pyla
min
eN
itro
so-2
6-d
imet
hylm
orph
olin
eN
itro
so-2
-oxo
prop
ylet
hano
lam
ine
Mon
key
1U
reth
anez
Rat
222-
Am
ino-
5-ni
trop
heno
ly 1-
( Am
inom
ethy
l)cy
cloh
exan
eace
ticac
idA
zase
rine
But
ylbe
nzyl
phth
alat
ey C
hlor
endi
cac
idz
Cin
nam
ylan
thra
nila
tez
Clo
bra
tey
Dic
hlor
vosz
Eth
ylal
coho
ly H
ydro
chlo
ro
uoro
carb
on12
3IQ
HC
lM
alon
alde
hyde
sod
ium
saltz
MeA
-a-C
acet
atez
2-M
erca
ptob
enzo
thia
zole
y M
ethy
lclo
fena
pate
z N
-(N
-Met
hyl-
N-n
itros
ocar
bam
oyl)
-l-o
rnit
hine
4-(
Met
hyln
itro
sam
ino)
-1-(
3-py
ridy
l)-1
-but
anol
4-(
Met
hyln
itros
amin
o)-1
-( 3
-pyr
idyl
) -1-
( but
anon
e)N
afen
opin
Nitr
ofen
z To
luen
edi
isoc
yana
tec
omm
erci
algr
ade
( 24
( 80
) -an
d2
6( 2
0) -
)z1
23
-Tri
chlo
ropr
opan
ez
Peri
tone
alM
ouse
8B
is-1
2-(
chlo
rom
etho
xy) e
than
eB
is-1
4-(
chlo
rom
etho
xy) -
p-xy
lene
Bis
-(ch
loro
met
hyl)
ethe
rz C
hlor
opre
nez
tran
s-1
4-D
ichl
orob
uten
e-2
cavi
tyD
imet
hylc
arba
myl
chlo
ride
Phe
noxy
benz
amin
eH
Clz
Tri
s-1
23-
( chl
orom
etho
xy) p
ropa
neR
at22
Acr
onyc
ine
Acr
ylam
ide
Act
inom
ycin
DA
nili
neH
Cly
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
rom
ate
pota
ssiu
mz
Chl
oroz
otoc
in
Cyt
embe
nay
Dap
sone
y 1
2-D
ibro
moe
than
ez D
ibro
mom
anni
tolz
33
-Dim
ethy
lben
zidi
ne2
HC
lz 1
4-D
ioxa
nez
Eth
ylen
eox
idez
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Gly
cido
lz M
elph
alan
z N
-Met
hyl-
N4
-din
itros
oani
line
Mit
omyc
in-C
N-N
itro
so-2
24
-tri
met
hyl-
12-
dihy
droq
uino
line
poly
mer
Ph
enox
yben
zam
ine
HC
lz o-
Tolu
idin
eH
Clz
( Con
tinue
don
next
page
)
645
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Pitu
itar
ygl
and
Mou
se8
Die
thyl
stil
best
rolz
Eno
vid
Eth
ylen
eth
iour
eaz
Iodi
nate
dgl
ycer
olz
Isop
rene
Nor
lest
rinz
Pro
pylt
hiou
raci
lz Z
eara
leno
ney
Rat
73-
Am
inot
riaz
olez
12-
Dib
rom
oeth
anez
Die
thyl
stil
best
rolz
Eth
ylal
coho
ly 2-
Mer
capt
oben
zoth
iazo
ley
Met
roni
dazo
lez
Nor
lest
rinz
Pros
tate
Rat
4C
adm
ium
chlo
ride
N-N
itros
obis
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ydro
xypr
opyl
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ine
N-N
itros
obis
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xopr
opyl
) am
ine
PhIP
HC
lz
Skin
Ham
ster
2U
reth
anez
Vin
ylch
lori
dez
Mou
se5
5-A
zacy
tidin
ez 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Chl
orop
rene
z G
lyci
dolz
Thi
o-te
paz
Rat
332-
Ace
tyla
min
ouo
rene
z 3-
Am
ino-
9-et
hylc
arba
zole
mix
ture
z 1-
Azo
xypr
opan
e2-
Azo
xypr
opan
eB
enze
nez
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
ol
tech
nica
lgra
dez
CI
dir
ectb
lue
15C
arbo
xym
ethy
lnitr
osou
rea
24-
Dia
min
oani
sole
sulf
atez
Dib
rom
odul
cito
lz D
ibro
mom
anni
tolz
Dim
etho
xane
2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 3
3-D
imet
hoxy
benz
idin
e-4
4-d
iisoc
yana
tey
33
-Dim
etho
xybe
nzid
ine
2HC
l3
3-D
imet
hylb
enzi
dine
2H
Clz
Dim
ethy
lvin
ylch
lori
dez
24-
Din
itro
tolu
ene
( con
tain
ing
10-
15
26-
dini
trot
olue
ne)z
1-E
thyl
nitr
oso-
3-( 2
-hyd
roxy
ethy
l)-u
rea
1-E
thyl
nitr
oso-
3-( 2
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prop
yl) -
urea
Gly
cido
lz 1-
( 2-H
ydro
xyet
hyl)
-nit
roso
-3-e
thyl
urea
IQ
z L
asio
carp
ine
MeI
Qxz
N-(
N-M
ethy
l-N
-nitr
osoc
arba
moy
l)-l
-orn
ithi
ne
5-N
itro-
o-an
isid
inez
CI
aci
dre
d11
4p-
Ros
anili
neH
Clz
Thi
o-te
paz
Thi
oure
ay V
inyl
chlo
ride
z F
Damp
Cvi
olet
no1
y
Smal
lint
esti
neM
ouse
6C
apta
folz
Cap
tanz
N-E
thyl
-N-n
itro
-N-n
itro
sogu
anid
ine
Hyd
roge
npe
roxi
deN
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hyl-
N-n
itro-
N-n
itros
ogua
nidi
nez
N-(
Tri
chlo
rom
ethy
lthi
o)ph
thal
imid
eM
onke
y1
Ure
than
ez
Rat
29A
cryl
onitr
ile
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
is( 2
3-d
ibro
mop
ropy
l)ph
osph
ate
mag
nesi
umsa
lt4
-Bis
( 2-h
ydro
xyet
hyl)
amin
o-2-
( 5-n
itro
-2-t
hien
yl) q
uina
zolin
eC
Id
irec
tblu
e15
Car
boxy
met
hyln
itros
oure
a1-
( 4-C
hlor
ophe
nyl)
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heny
l-2-
prop
ynyl
carb
amat
e2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 3
3-D
imet
hoxy
benz
idin
e2H
Cl
46-
Dim
ethy
l-2-
( 5-n
itro
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uryl
)py
rim
idin
etr
ans-
2-[(
Dim
ethy
lam
ino)
met
hylim
ino]
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2-( 5
-nit
ro-2
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yl) v
inyl
] -1
34-
oxad
iazo
le3
3-D
imet
hylb
enzi
dine
2H
Clz
Z-E
thyl
-ON
N-a
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met
hane
1-E
thyl
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itros
oure
aFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z G
lu-P
-1z
Glu
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z IQ
z L
asio
carp
ine
N-M
ethy
l-N
-nitr
o-N
-nitr
osog
uani
dine
z N
-[5-
( 5-N
itro-
2-fu
ryl)
-13
4-t
hiad
iazo
l-2-
yl] a
ceta
mid
ez N
-Nitr
oso-
N-i
sobu
tylu
rea
3-N
itro
so-2
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zoli
dino
neN
itro
soet
hylu
reth
ane
PhI
PH
Clz
Pro
pane
sulto
neQ
uerc
etin
y C
Ia
cid
red
114
Trp
-P-2
acet
atez
Sple
enR
at7
Ani
line
HC
ly A
zobe
nzen
ey p-
Chl
oroa
nili
neH
Clz
Dap
sone
y o-
Nitr
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olue
neD
ampC
red
no9
y o-
Tolu
idin
eH
Clz
Stom
ach
Ham
ster
18A
F-2z
14-
Din
itros
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6-di
met
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azin
eFo
rmic
acid
2-[ 4
-(5-
nitr
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fury
l)-2
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azol
yl] h
ydra
zide
z H
ydra
zine
z N
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roxy
-2-a
cety
lam
ino
uore
nez
N-[
4-( 5
-Nitr
o-2-
fury
l)-2
-thi
azol
yl] a
ceta
mid
eN
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] for
mam
idez
N-N
itro
so-2
3-d
ihyd
roxy
prop
yl-2
-hyd
roxy
prop
ylam
ine
Nitr
oso-
23-
dihy
drox
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pyl-
2-ox
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pyla
min
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ethy
l-2-
oxop
ropy
lure
aN
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aN
itros
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met
hylo
xazo
lidon
eN
-Nit
roso
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ethy
lure
than
N-N
itros
o-1
3-ox
azol
idin
eN
-Nit
roso
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heny
leth
ylur
ea1
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roso
-34
5-t
rim
ethy
lpip
eraz
ine
Ure
than
ez V
inyl
chlo
ride
z
Mou
se63
Ace
tald
ehyd
em
ethy
lfor
myl
hydr
azon
eA
ciu
orfe
nA
F-2
z 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 2-
Am
ino-
4-( 5
-nitr
o-2-
fury
l)th
iazo
lez
tran
s-5-
Am
ino-
3[2-
( 5-n
itro-
2-fu
ryl)
viny
l] -1
24-
oxad
iazo
leA
reco
line
HC
lB
enza
ldeh
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Ben
zofu
ranz
Ben
zotr
ichl
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enzy
lace
tate
y B
enzy
lchl
orid
ey B
rom
oeth
anol
13
-But
adie
nez
But
ylat
edhy
drox
yani
sole
z 1
1-di
-N-B
utyl
hydr
azin
eC
affe
icac
idz
Cap
tafo
lz C
arba
zole
Cat
echo
lz 3-
Chl
oro-
2-m
ethy
lpro
pene
tec
hnic
algr
ade
( con
tain
ing
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met
hylv
inyl
chlo
ride
)z3
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hlor
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HC
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hlor
opre
nez
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hlor
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pana
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Chl
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neC
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neac
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1-D
ially
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razi
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2-D
ibro
mo-
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loro
prop
anez
12-
Dib
rom
oeth
anez
Dic
hlor
vosz
Dig
lyci
dylr
esor
cino
leth
ert
echn
ical
grad
ez D
imet
hylv
inyl
chlo
ride
z D
init
roso
pipe
razi
neE
stra
diol
mus
tard
y E
thyl
acry
late
z Fo
rmic
acid
2-[ 4
-( 5
-nit
ro-2
-fur
yl) -
2-th
iazo
lyl] h
ydra
zide
z G
lyci
dolz
2-H
ydra
zino
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5-ni
tro-
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ryl)
thia
zole
z N
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roxy
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cety
lam
ino
uore
nez
ICI
1628
46z
IQz
Isop
rene
Lov
asta
tin
MeI
Q1
-Met
hyl-
14-
dihy
dro-
7-[ 2
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nitr
ofur
yl) v
inyl
] -4-
oxo-
18-
naph
thyr
idin
e-3-
carb
oxyl
ate
pota
ssiu
m3
-(5-
Nitr
o-2-
fury
l)-
imid
azo(
12-
a) p
yrid
inez
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
N-[
4-( 5
-Nitr
o-2-
fury
l)-2
-thi
azol
yl] f
orm
amid
ez N
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roso
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-met
hylu
reaz
Nit
roso
dibu
tyla
min
ez N
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roso
hexa
met
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neim
ine
N-N
itros
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erid
inez
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ropi
olac
tone
z Se
sam
olz
Sty
rene
oxid
ez Te
lone
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echn
ical
grad
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rich
loro
met
hylth
io) p
htha
limid
e1
23-
Tri
chlo
ropr
opan
ez 2
22-
Tri
uo
ro-N
-[4-
( 5-n
itro
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uryl
) -2-
thia
zoly
l]ac
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idez
Tri
ur
alin
tec
hnic
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adey
Tri
s(2-
chlo
roet
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phos
phat
ez T
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23-
dibr
omop
ropy
l)ph
osph
atez
Vin
ylac
etat
ez
Rat
85A
ceto
ne[ 4
-(5-
nitr
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fury
l)-2
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azol
yl] h
ydra
zone
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frol
ey A
cryl
onitr
ile
1-A
llyl
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itro
sour
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ino-
5-( 5
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ro-2
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yl) -
13
4-ox
adia
zole
2-
Am
ino-
5-( 5
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fury
l)-1
34
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adia
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2-A
min
o-4-
( 5-n
itro
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uryl
) thi
azol
ez 1-
Am
yl-1
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roso
urea
Ari
stol
ochi
cac
id
sodi
umsa
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7A
AI
21
AA
II)
Ben
zene
z B
enzo
( a) p
yren
ez 2
2-B
is( b
rom
omet
hyl)
-13
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pane
diol
tec
hnic
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adez
Bis
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rom
opro
pyl)
phos
phat
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agne
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salt
BL
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1H
Cl
N-n
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yl-N
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rea
But
ylat
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sole
z b
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yrol
acto
neC
affe
icac
idz
Cat
echo
lz 3-
Chl
oro-
2-m
ethy
lpro
pene
tec
hnic
algr
ade
( con
tain
ing
5di
met
hylv
inyl
chlo
ride
)z4
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oro-
o-ph
enyl
ened
iam
inez
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oro
uoro
met
hane
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( Chl
orom
ethy
l)py
ridi
neH
Clz
Cip
rob
rate
z C
upfe
rron
z 1
2-D
ibro
mo-
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prop
anez
12-
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rom
oeth
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Dic
hlor
oeth
anez
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lyci
dylr
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cino
leth
ert
echn
ical
grad
ez 2
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imet
hoxy
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min
osti
lben
ez D
imet
hylh
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gen
phos
phit
ey 4
6-D
imet
hyl-
2-( 5
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ro-2
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ryl)
pyri
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ine
tran
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imet
hyla
min
o)m
ethy
limin
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( 5-n
itro
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uryl
) vin
yl] -
13
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adia
zole
Dim
ethy
lvin
ylch
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dez
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chlo
rohy
drin
y E
thyl
acry
late
z E
thyl
ene
oxid
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oroe
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rea
Gly
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roxy
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prop
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ICI
1628
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Lox
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nez
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ethy
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roso
benz
amid
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Met
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Met
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itro
socy
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ide
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yl) -
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12-
a) p
yrid
inez
N-[
5-( 5
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ro-2
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yl) -
13
4-th
iadi
azol
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l] ace
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idez
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prop
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Subc
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Mou
se4
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mom
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ical
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Tolu
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Rat
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mom
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l)-1
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ical
grad
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z N
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yl-N
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hydr
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Cad
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Mou
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sole
sulf
atez
Die
thyl
stil
best
rolz
Dox
ylam
ine
succ
inat
ez E
thio
nam
idey
Eth
ylen
eth
iour
eaz
44
-Met
hyle
nedi
anil
ine
2HC
lz 1
5-N
apht
hale
nedi
amin
ez N
itrob
enze
nez
Oxa
zepa
my
44
-Oxy
dian
iline
z C
Ip
igm
entr
ed3z
Sulf
amet
hazi
ne2
37
8-T
etra
chlo
rodi
benz
o-p-
diox
inz
44
-Thi
odia
nilin
ez
Rat
33A
cryl
amid
e3-
Am
inot
riaz
olez
o-A
nisi
dine
HC
lz B
emit
radi
ne2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Bro
mat
epo
tass
ium
z C
hlor
inat
edpa
raf
ns( C
126
0ch
lori
ne)z
Chl
orop
rene
z 2
4-D
iam
inoa
niso
lesu
lfat
ez N
N-D
ieth
ylth
iour
eay
1-E
thyl
-1-n
itro
sour
ea
Eth
ylen
eth
iour
eaz
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Flu
vast
atin
Gly
cido
lz Io
dina
ted
glyc
erol
z Is
obut
eney
Mal
onal
dehy
des
odiu
msa
ltz
Met
him
azol
e4
4-M
ethy
lene
bis(
NN
-dim
ethy
l)be
nzen
amin
ez 4
4-M
ethy
lene
dian
iline
2H
Clz
Mir
exp
hoto
-N
itro
benz
enez
N-N
itro
sobi
s(2-
oxop
ropy
l)am
ine
44
-Oxy
dian
iline
z Pr
opyl
thio
urac
ilz p-
Ros
anil
ine
HC
lz 2
37
8-Te
trac
hlor
odib
enzo
-p-d
ioxi
nz 4
4-T
hiod
iani
linez
Thi
oura
cilz
Tri
met
hylt
hiou
reay
Vin
ylac
etat
ez Z
inc
dim
ethy
ldith
ioca
rbam
atez
Uri
nary
blad
der
Dog
23
3-D
ichl
orob
enzi
dine
44
-Met
hyle
ne-b
is( 2
-chl
oroa
nilin
e)H
amst
er3
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-t
hiaz
olyl
] hyd
razi
dez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
acet
amid
eN
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] for
mam
idez
Mou
se12
2-A
cety
lam
ino
uore
nez
4-A
min
odip
heny
l2-
Am
inod
iphe
nyle
neox
ide
o-A
nisi
dine
HC
lz 4-
Chl
oro-
4-a
min
odip
heny
leth
erz
p-C
resi
dine
z 4-
Eth
ylsu
lpho
nyln
apht
hale
ne-1
-sul
fona
mid
eN
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez P
hena
cetin
z Te
lone
IIt
echn
ical
grad
ez U
raci
lz
Mon
key
12-
Nap
hthy
lam
inez
Rat
49A
ceta
min
ophe
nz A
llyli
soth
iocy
anat
ey 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 2-
Am
ino-
4-( 5
-nitr
o-2-
fury
l)th
iazo
lez
4-A
min
o-2-
nitr
ophe
noly
11-A
min
ound
ecan
oic
acid
y o-
Ani
sidi
neH
Clz
Ari
stol
ochi
cac
ids
odiu
msa
lt( 7
7A
AI
21
AA
II)
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez C
Id
ispe
rse
blue
1y N
-But
yl-N
-(4-
hydr
oxyb
utyl
) nitr
osam
ine
4-C
hlor
o-o-
phen
ylen
edia
min
ez m
-Cre
sidi
ney
p-C
resi
dine
z C
yclo
phos
pham
idez
Die
thyl
ene
glyc
olD
imet
hyla
rsin
icac
idy
Fose
tylA
lIQ
HC
lM
eA-a
-Cac
etat
ez M
elam
iney
2-M
etho
xy-3
-am
inod
iben
zofu
ran
2-N
apht
hyla
min
ez N
itril
otri
acet
icac
idz
Nitr
ilot
riac
etic
acid
tri
sodi
umsa
ltm
onoh
ydra
tey
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez o-
Nitr
oani
sole
z N
-Nitr
oso-
N-m
ethy
l-N
-dod
ecyl
amin
eN
-Nitr
oso-
N-m
ethy
l-N
-tet
rade
cyla
min
eN
-Nit
roso
-N-m
ethy
ldec
ylam
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
Nitr
osod
ibut
ylam
inez
N-N
itro
sodi
phen
ylam
iney
o-N
itros
otol
uene
N-O
xydi
ethy
lene
thio
carb
amyl
-N-o
xydi
ethy
lene
sulf
enam
ide
Phe
nace
tinz
Phen
azon
eo-
Phen
ylph
enat
eso
dium
y o-
Phen
ylph
enol
y P
otas
sium
bica
rbon
ate
Purp
urin
Que
rcet
iny
p-Q
uino
nedi
oxim
ey Sa
ccha
rin
sodi
umy
Sali
cyla
zosu
lfap
yrid
inez
o-To
luen
esul
fona
mid
eo-
Tolu
idin
eH
Clz
Trp
-P-2
acet
atez
Ura
cilz
Ute
rus
Ham
ster
1N
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aM
ouse
12B
rom
oeth
anez
Chl
oroe
than
ey D
acar
bazi
nez
12-
Dic
hlor
oeth
anez
Die
thyl
stil
best
rolz
Eth
ylen
eox
idez
Gly
cido
lz ( N
-6) -
( Met
hyln
itros
o)ad
enos
ine
Proc
arba
zine
HC
lz 1
23-
Tri
chlo
ropr
opan
ez T
rim
ethy
lpho
spha
tey
Vin
ylac
etat
ez
Rat
26A
cryl
amid
e1-
Ally
l-1-
nitr
osou
rea
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
1-A
myl
-1-n
itros
oure
aA
traz
iney
CI
dir
ectb
lue
15B
rom
ocri
ptin
em
esyl
atey
N-n
-But
yl-N
-nit
roso
urea
Cal
cium
valp
roat
eC
apta
nz 2-
Chl
oro-
11
1-tr
iuo
roet
hane
Dac
arba
zine
z D
amin
ozid
ez 3
3-D
imet
hoxy
benz
idin
e-4
4-d
iisoc
yana
tey
33
-Dim
etho
xybe
nzid
ine
2HC
lD
imet
hyla
min
oeth
ylni
tros
oeth
ylur
ean
itri
tesa
lt1-
Eth
ylni
tros
o-3-
( 2-h
ydro
xyet
hyl)
-ure
a1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
N-H
exyl
nitr
osou
rea
ICR
F-1
59z
Isop
hosp
ham
idez
15-
Nap
htha
lene
diam
inez
Nit
robe
nzen
ez N
orle
stri
nz 4
4-T
hiod
iani
linez
Vin
ylac
etat
ez
Vag
ina
Mou
se1
AZ
Tz
Rat
2A
ZT
z N
-n-B
utyl
-N-n
itro
sour
ea( C
ontin
ued
onne
xtpa
ge)
647
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Vas
cula
rsy
stem
Ham
ster
91
2-D
imet
hylh
ydra
zine
2H
Cl
Gly
cido
lz H
exac
hlor
oben
zene
z N
-Nit
roso
-eth
yl-2
-oxo
prop
ylur
eaN
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aN
-Nitr
oso-
oxop
ropy
lchl
oroe
thyl
urea
N-N
itro
so-o
xopr
opyl
urea
N-N
itros
o-2-
phen
ylet
hylu
rea
Vin
ylch
lori
dez
Mou
se59
A-a
-CN
-Ace
tyl-
4-( h
ydro
xym
ethy
l)ph
enyl
hydr
azin
e1-
Ace
tyl-
2-ph
enyl
hydr
azin
eA
llyl
hydr
azin
eH
Cl
Are
colin
eH
Cl
Aza
thio
prin
eB
enzi
dine
2H
Cl
2-B
iphe
nyla
min
eH
Cly
13-
But
adie
nez
Cap
tafo
lz C
arba
myl
hydr
azin
eH
Cl
4-C
hlor
o-4
-am
inod
iphe
nyle
ther
z 1-
Chl
oro-
4-ni
trob
enze
ney
5-C
hlor
o-o-
tolu
idin
ey 4-
Chl
oro-
o-to
luid
ine
HC
ly p-
Chl
oroa
nilin
eH
Clz
Chl
orop
rene
z C
upfe
rron
z D
acar
bazi
nez
Dam
inoz
idez
24-
Dia
min
otol
uene
2H
Clz
12-
Dib
rom
oeth
anez
Dif
talo
ne7
12-
Dim
ethy
lben
z(a)
anth
race
ne1
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
N-E
thyl
-N-f
orm
ylhy
draz
ine
Eth
ylhy
draz
ine
HC
lG
lu-P
-1z
Glu
-P-2
z p-
Hyd
razi
nobe
nzoi
cac
idH
Cl
1-H
ydro
xysa
frol
ez Is
opre
neM
eA-a
-Cac
etat
ez N
-Met
hyl-
N-f
orm
ylhy
draz
ine
2-M
ethy
l-1-
nitr
oant
hraq
uino
nez
Mic
hler
rsquoske
tone
z 5-
Nitr
o-o-
tolu
idin
ey N
itro
fenz
N-N
itros
o-N
-met
hylu
reaz
Pent
achl
oroa
niso
lez
23
45
6-Pe
ntac
hlor
ophe
nol(
Dow
icid
eE
C-7
)y2
34
56
-Pen
tach
loro
phen
olt
echn
ical
grad
ez n-
Pen
tylh
ydra
zine
HC
lPh
enyl
ethy
lhyd
razi
nesu
lfat
ePh
enyl
hydr
azin
eH
Cl
Ster
igm
atoc
ysti
nz Te
tra
uoro
ethy
lene
z To
luen
edi
isoc
yana
tec
omm
erci
algr
ade
( 24
( 80
) -an
d2
6( 2
0) -
)zo
-Tol
uidi
neH
Clz
24
6-T
rich
loro
anil
iney
24
5-T
rim
ethy
lani
line
HC
lz 2
46-
Tri
met
hyla
nili
neH
Clz
Ure
than
ez V
inyl
carb
amat
eV
inyl
chlo
ride
z V
inyl
uor
idez
Vin
ylid
ene
chlo
ride
y 2
5-X
ylid
ine
HC
lz
Mon
key
2A
ato
xin
B1y
Ure
than
ez
Rat
32A
nilin
eH
Cly
Azo
benz
eney
Ben
zene
z C
livor
ine
Cup
ferr
onz
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
Z-E
thyl
-ON
N-a
zoxy
etha
neZ
-Eth
yl-O
NN
-azo
xym
etha
neI
QH
Cl
Las
ioca
rpin
e4
4-M
ethy
lene
-bis
( 2-c
hlor
oani
line)
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
N-N
itros
o-( 2
-hyd
roxy
prop
yl) -
( 2-h
ydro
xyet
hyl)
amin
eN
itro
so-1
23
6-t
etra
hydr
opyr
idin
eN
-Nitr
osob
is( 2
-oxo
prop
yl) a
min
eN
-Nit
roso
diet
hano
lam
ine
N-N
itro
sodi
ethy
lam
ine
N-N
itros
odim
ethy
lam
inez
N-N
itros
omet
hyl-
( 2-t
osyl
oxye
thyl
) am
ine
N-N
itros
omor
phol
ine
N-N
itro
sopy
rrol
idin
ez Pe
tasi
teni
neS
teri
gmat
ocys
tinz
Sym
phyt
ine
Tetr
auo
roet
hyle
nez
o-To
luid
ine
HC
lz T
rp-P
-2ac
etat
ez V
inyl
brom
ide
Vin
ylch
lori
dez
Vin
yl
uori
dez
aT
here
was
nore
port
edta
rget
site
in1
spec
ies
( rat
sor
mic
e)fo
r5
chem
ical
sw
ithsu
pers
crip
tsb
utth
ech
emic
alw
asev
alua
ted
byth
epu
blis
hed
auth
oras
aca
rcin
ogen
ald
rinz
diel
drin
z N
-nit
roso
pyrr
olid
inez
23
45
6-pe
ntac
hlor
ophe
nol
( Dow
icid
eE
C-7
)ya
ndur
etha
nez
bN
asal
cavi
tyin
clud
estis
sues
ofth
eno
sen
asal
turb
inat
esp
aran
asal
sinu
ses
and
trac
hea
c Ora
lcav
ityin
clud
estis
sues
ofth
em
outh
oro
phar
ynx
phar
ynx
and
lary
nx
Ach
emic
alis
liste
dun
der
each
orga
nev
alua
ted
aspo
sitiv
ein
anex
peri
men
tin
that
spec
ies
byat
leas
t1au
thor
The
refo
rea
chem
ical
may
beli
sted
unde
rse
vera
ltar
geto
rgan
san
dev
ery
chem
ical
liste
din
the
tabl
eis
posi
tive
inat
leas
t1sp
ecie
sIn
orde
rto
com
pare
resu
ltsin
rats
and
mic
esy
mbo
lsfo
llow
chem
ical
ste
sted
inbo
thsp
ecie
sa
zin
dica
tes
that
the
chem
ical
ispo
sitiv
eat
som
esi
tein
both
spec
ies
and
ay
indi
cate
sth
atit
was
test
edin
both
butp
ositi
vein
only
1a
Nth
enu
mbe
rof
chem
ical
sw
ithat
leas
t1po
sitiv
ete
stat
that
site
inth
atsp
ecie
sB
ecau
sem
any
chem
ical
sin
duce
tum
ors
atm
ore
than
1si
tein
agi
ven
spec
ies
man
ych
emic
als
appe
arm
ore
than
once
inth
eta
ble
648
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649
species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters
RESULTS IN RATS AND MICE
For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens
TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database
Chemicals evaluated as carcinogenic in
Rats Mice
All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)
Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2
a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not
b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats
All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical
to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included
The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site
Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common
650 GOLD ET AL TOXICOLOGIC PATHOLOGY
TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)
Target site Agent mixture or industrial process
Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e
Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke
Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products
Brain Vinyl chloride a
Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e
Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena
Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system
Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as
a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell
lymphotropic virus type I (HTLV-I) Vinyl chloridea
Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production
Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)
Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea
Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea
Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)
Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea
Mesenchymal tumors Azathioprinea
Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust
Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust
Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid
(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke
Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production
8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots
Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e
Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays
IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD
IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no
tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance
is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651
sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites
Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to
be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)
Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)
Target Organs of Human CarcinogensTo complement the compendium of target organs in car-
cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke
In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)
Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens
Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from
bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)
ACKNOWLEDGMENTS
We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention
REFERENCES
1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56
2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600
3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998
4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685
5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404
6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605
7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246
8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100
9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash
23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC
11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the
652 GOLD ET AL TOXICOLOGIC PATHOLOGY
US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240
12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute
13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program
14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX
15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11
16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash
34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c
Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Pitu
itar
ygl
and
Mou
se8
Die
thyl
stil
best
rolz
Eno
vid
Eth
ylen
eth
iour
eaz
Iodi
nate
dgl
ycer
olz
Isop
rene
Nor
lest
rinz
Pro
pylt
hiou
raci
lz Z
eara
leno
ney
Rat
73-
Am
inot
riaz
olez
12-
Dib
rom
oeth
anez
Die
thyl
stil
best
rolz
Eth
ylal
coho
ly 2-
Mer
capt
oben
zoth
iazo
ley
Met
roni
dazo
lez
Nor
lest
rinz
Pros
tate
Rat
4C
adm
ium
chlo
ride
N-N
itros
obis
( 2-h
ydro
xypr
opyl
) am
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
PhIP
HC
lz
Skin
Ham
ster
2U
reth
anez
Vin
ylch
lori
dez
Mou
se5
5-A
zacy
tidin
ez 2
2-B
is( b
rom
omet
hyl)
-13
-pro
pane
diol
tec
hnic
algr
adez
Chl
orop
rene
z G
lyci
dolz
Thi
o-te
paz
Rat
332-
Ace
tyla
min
ouo
rene
z 3-
Am
ino-
9-et
hylc
arba
zole
mix
ture
z 1-
Azo
xypr
opan
e2-
Azo
xypr
opan
eB
enze
nez
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
ol
tech
nica
lgra
dez
CI
dir
ectb
lue
15C
arbo
xym
ethy
lnitr
osou
rea
24-
Dia
min
oani
sole
sulf
atez
Dib
rom
odul
cito
lz D
ibro
mom
anni
tolz
Dim
etho
xane
2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 3
3-D
imet
hoxy
benz
idin
e-4
4-d
iisoc
yana
tey
33
-Dim
etho
xybe
nzid
ine
2HC
l3
3-D
imet
hylb
enzi
dine
2H
Clz
Dim
ethy
lvin
ylch
lori
dez
24-
Din
itro
tolu
ene
( con
tain
ing
10-
15
26-
dini
trot
olue
ne)z
1-E
thyl
nitr
oso-
3-( 2
-hyd
roxy
ethy
l)-u
rea
1-E
thyl
nitr
oso-
3-( 2
-oxo
prop
yl) -
urea
Gly
cido
lz 1-
( 2-H
ydro
xyet
hyl)
-nit
roso
-3-e
thyl
urea
IQ
z L
asio
carp
ine
MeI
Qxz
N-(
N-M
ethy
l-N
-nitr
osoc
arba
moy
l)-l
-orn
ithi
ne
5-N
itro-
o-an
isid
inez
CI
aci
dre
d11
4p-
Ros
anili
neH
Clz
Thi
o-te
paz
Thi
oure
ay V
inyl
chlo
ride
z F
Damp
Cvi
olet
no1
y
Smal
lint
esti
neM
ouse
6C
apta
folz
Cap
tanz
N-E
thyl
-N-n
itro
-N-n
itro
sogu
anid
ine
Hyd
roge
npe
roxi
deN
-Met
hyl-
N-n
itro-
N-n
itros
ogua
nidi
nez
N-(
Tri
chlo
rom
ethy
lthi
o)ph
thal
imid
eM
onke
y1
Ure
than
ez
Rat
29A
cryl
onitr
ile
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez B
is( 2
3-d
ibro
mop
ropy
l)ph
osph
ate
mag
nesi
umsa
lt4
-Bis
( 2-h
ydro
xyet
hyl)
amin
o-2-
( 5-n
itro
-2-t
hien
yl) q
uina
zolin
eC
Id
irec
tblu
e15
Car
boxy
met
hyln
itros
oure
a1-
( 4-C
hlor
ophe
nyl)
-1-p
heny
l-2-
prop
ynyl
carb
amat
e2
5-D
imet
hoxy
-4-a
min
ostil
bene
z 3
3-D
imet
hoxy
benz
idin
e2H
Cl
46-
Dim
ethy
l-2-
( 5-n
itro
-2-f
uryl
)py
rim
idin
etr
ans-
2-[(
Dim
ethy
lam
ino)
met
hylim
ino]
-5-[
2-( 5
-nit
ro-2
-fur
yl) v
inyl
] -1
34-
oxad
iazo
le3
3-D
imet
hylb
enzi
dine
2H
Clz
Z-E
thyl
-ON
N-a
zoxy
met
hane
1-E
thyl
-1-n
itros
oure
aFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z G
lu-P
-1z
Glu
-P-2
z IQ
z L
asio
carp
ine
N-M
ethy
l-N
-nitr
o-N
-nitr
osog
uani
dine
z N
-[5-
( 5-N
itro-
2-fu
ryl)
-13
4-t
hiad
iazo
l-2-
yl] a
ceta
mid
ez N
-Nitr
oso-
N-i
sobu
tylu
rea
3-N
itro
so-2
-oxa
zoli
dino
neN
itro
soet
hylu
reth
ane
PhI
PH
Clz
Pro
pane
sulto
neQ
uerc
etin
y C
Ia
cid
red
114
Trp
-P-2
acet
atez
Sple
enR
at7
Ani
line
HC
ly A
zobe
nzen
ey p-
Chl
oroa
nili
neH
Clz
Dap
sone
y o-
Nitr
osot
olue
neD
ampC
red
no9
y o-
Tolu
idin
eH
Clz
Stom
ach
Ham
ster
18A
F-2z
14-
Din
itros
o-2
6-di
met
hylp
iper
azin
eFo
rmic
acid
2-[ 4
-(5-
nitr
o-2-
fury
l)-2
-thi
azol
yl] h
ydra
zide
z H
ydra
zine
z N
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
N-[
4-( 5
-Nitr
o-2-
fury
l)-2
-thi
azol
yl] a
ceta
mid
eN
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] for
mam
idez
N-N
itro
so-2
3-d
ihyd
roxy
prop
yl-2
-hyd
roxy
prop
ylam
ine
Nitr
oso-
23-
dihy
drox
ypro
pyl-
2-ox
opro
pyla
min
eN
-Nitr
oso-
ethy
l-2-
oxop
ropy
lure
aN
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aN
itros
o-5-
met
hylo
xazo
lidon
eN
-Nit
roso
-N-m
ethy
lure
than
N-N
itros
o-1
3-ox
azol
idin
eN
-Nit
roso
-2-p
heny
leth
ylur
ea1
-Nit
roso
-34
5-t
rim
ethy
lpip
eraz
ine
Ure
than
ez V
inyl
chlo
ride
z
Mou
se63
Ace
tald
ehyd
em
ethy
lfor
myl
hydr
azon
eA
ciu
orfe
nA
F-2
z 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 2-
Am
ino-
4-( 5
-nitr
o-2-
fury
l)th
iazo
lez
tran
s-5-
Am
ino-
3[2-
( 5-n
itro-
2-fu
ryl)
viny
l] -1
24-
oxad
iazo
leA
reco
line
HC
lB
enza
ldeh
ydey
Ben
zofu
ranz
Ben
zotr
ichl
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lace
tate
y B
enzy
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orid
ey B
rom
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anol
13
-But
adie
nez
But
ylat
edhy
drox
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sole
z 1
1-di
-N-B
utyl
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azin
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affe
icac
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Cap
tafo
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arba
zole
Cat
echo
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Chl
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ethy
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tec
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ade
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tain
ing
5di
met
hylv
inyl
chlo
ride
)z3
-(C
hlor
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HC
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nez
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pana
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Chl
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tero
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ially
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razi
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mo-
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loro
prop
anez
12-
Dib
rom
oeth
anez
Dic
hlor
vosz
Dig
lyci
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cino
leth
ert
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ical
grad
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imet
hylv
inyl
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ride
z D
init
roso
pipe
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stra
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mus
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thyl
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late
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rmic
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2-[ 4
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yl) -
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iazo
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ydra
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z G
lyci
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ryl)
thia
zole
z N
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cety
lam
ino
uore
nez
ICI
1628
46z
IQz
Isop
rene
Lov
asta
tin
MeI
Q1
-Met
hyl-
14-
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dro-
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inyl
] -4-
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18-
naph
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idin
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carb
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ate
pota
ssiu
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-(5-
Nitr
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l)-
imid
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12-
a) p
yrid
inez
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
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l] ace
tam
idez
N-[
4-( 5
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fury
l)-2
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azol
yl] f
orm
amid
ez N
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reaz
Nit
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min
ez N
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met
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ine
N-N
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inez
b-P
ropi
olac
tone
z Se
sam
olz
Sty
rene
oxid
ez Te
lone
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echn
ical
grad
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-(T
rich
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met
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io) p
htha
limid
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23-
Tri
chlo
ropr
opan
ez 2
22-
Tri
uo
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( 5-n
itro
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thia
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l]ac
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Tri
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alin
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Tri
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chlo
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23-
dibr
omop
ropy
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osph
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Vin
ylac
etat
ez
Rat
85A
ceto
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yl] h
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cryl
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ino-
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13
4-ox
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34
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2-A
min
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azol
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Am
yl-1
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Ari
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id
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7A
AI
21
AA
II)
Ben
zene
z B
enzo
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rom
omet
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Bis
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rom
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agne
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1H
Cl
N-n
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But
ylat
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neC
affe
icac
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Cat
echo
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lpro
pene
tec
hnic
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ade
( con
tain
ing
5di
met
hylv
inyl
chlo
ride
)z4
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oro-
o-ph
enyl
ened
iam
inez
Chl
oro
uoro
met
hane
3-
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ethy
l)py
ridi
neH
Clz
Cip
rob
rate
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rom
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Dic
hlor
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Dig
lyci
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leth
ert
echn
ical
grad
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imet
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osti
lben
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imet
hylh
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gen
phos
phit
ey 4
6-D
imet
hyl-
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ryl)
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mid
ine
tran
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imet
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min
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ethy
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itro
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uryl
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yl] -
13
4-ox
adia
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Dim
ethy
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ylch
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dez
Epi
chlo
rohy
drin
y E
thyl
acry
late
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thyl
ene
oxid
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oroe
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rea
Gly
cido
lz N
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oure
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roxy
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inon
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xyet
hyl)
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nitr
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1-( 3
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roxy
prop
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oure
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olez
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1628
46z
Lox
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eL
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idin
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Mer
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phen
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N-n
itro-
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itros
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nez
N-M
ethy
l-N
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roso
benz
amid
e4-
Met
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atec
hol
Met
hyln
itro
socy
anam
ide
3-( 5
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yl) -
imid
azo(
12-
a) p
yrid
inez
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
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l] ace
tam
idez
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yl) t
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ole
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rene
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olin
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ropy
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ine
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Nit
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36
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ron
Nitr
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inez
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mep
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Phen
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Piv
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ney
b-P
ropi
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tone
z N
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12-
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pyle
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z St
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Sulf
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Telo
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tec
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rich
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prop
anez
24
6-T
rim
ethy
lani
line
HC
lz
646
Subc
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eous
Mou
se4
22-
Bis
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mom
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nedi
olt
echn
ical
grad
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than
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olt
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ical
grad
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4-D
iam
inot
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HC
lz 1
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ichl
oroe
than
ez D
imet
hoxa
ne1
4-D
ioxa
nez
MeA
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acet
atez
44
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hyle
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hyla
nili
ne)
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itro
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luen
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neH
Clz
Tolu
ene
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nate
com
mer
cial
grad
e( 2
4( 8
0) -
and
26
( 20
) -)z
o-T
olui
dine
HC
lz 2
45-
Tri
met
hyla
nilin
eH
Clz
25-
Xyl
idin
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Clz
Test
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ouse
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pine
z Ta
mox
ifen
citr
atez
Rat
185-
Aza
cytid
inez
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez 1
3-B
utad
iene
z N
-But
yl-N
-(4-
hydr
oxyb
utyl
) nitr
osam
ine
Cad
miu
mch
lori
de
2-C
hlor
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11-
tri
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1-D
ichl
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than
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rou
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3M
ethy
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tyle
ther
z M
ethy
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pate
z M
etro
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z N
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roso
dim
ethy
lam
inez
Oxo
linic
acid
y SD
Z20
0-11
01
11
2-Te
tra
uoro
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ney
Tri
chlo
roet
hyle
nez
Tri
nitr
ogly
ceri
nV
inyl
chlo
ride
z
Thy
roid
glan
dH
amst
er4
Hex
achl
orob
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nez
Hyd
razi
nez
Met
hylt
hiou
raci
lU
reth
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Mou
se18
3-A
min
o-4-
etho
xyac
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ilide
y H
Cbl
ueno
1z
tert
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ylal
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lz C
hlor
inat
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126
0ch
lori
ne)z
24
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min
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sole
sulf
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Die
thyl
stil
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Dox
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ine
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ez E
thio
nam
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Eth
ylen
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iour
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nedi
anil
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5-N
apht
hale
nedi
amin
ez N
itrob
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nez
Oxa
zepa
my
44
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iline
z C
Ip
igm
entr
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Sulf
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37
8-T
etra
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benz
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inz
44
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odia
nilin
ez
Rat
33A
cryl
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Am
inot
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HC
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emit
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rom
omet
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Bro
mat
epo
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ium
z C
hlor
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raf
ns( C
126
0ch
lori
ne)z
Chl
orop
rene
z 2
4-D
iam
inoa
niso
lesu
lfat
ez N
N-D
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iour
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1-E
thyl
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itro
sour
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Eth
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eth
iour
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1-E
thyl
nitr
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prop
yl) -
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Flu
vast
atin
Gly
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lz Io
dina
ted
glyc
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z Is
obut
eney
Mal
onal
dehy
des
odiu
msa
ltz
Met
him
azol
e4
4-M
ethy
lene
bis(
NN
-dim
ethy
l)be
nzen
amin
ez 4
4-M
ethy
lene
dian
iline
2H
Clz
Mir
exp
hoto
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itro
benz
enez
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itro
sobi
s(2-
oxop
ropy
l)am
ine
44
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dian
iline
z Pr
opyl
thio
urac
ilz p-
Ros
anil
ine
HC
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37
8-Te
trac
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enzo
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4-T
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iani
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Thi
oura
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Tri
met
hylt
hiou
reay
Vin
ylac
etat
ez Z
inc
dim
ethy
ldith
ioca
rbam
atez
Uri
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Dog
23
3-D
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dine
44
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oroa
nilin
e)H
amst
er3
Form
icac
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5-ni
tro-
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ryl)
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hiaz
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] hyd
razi
dez
N-[
4-( 5
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ro-2
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yl) -
2-th
iazo
lyl]
acet
amid
eN
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] for
mam
idez
Mou
se12
2-A
cety
lam
ino
uore
nez
4-A
min
odip
heny
l2-
Am
inod
iphe
nyle
neox
ide
o-A
nisi
dine
HC
lz 4-
Chl
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4-a
min
odip
heny
leth
erz
p-C
resi
dine
z 4-
Eth
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lam
ino
uore
nez
N-[
4-( 5
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ro-2
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yl) -
2-th
iazo
lyl]
form
amid
ez P
hena
cetin
z Te
lone
IIt
echn
ical
grad
ez U
raci
lz
Mon
key
12-
Nap
hthy
lam
inez
Rat
49A
ceta
min
ophe
nz A
llyli
soth
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Am
ino-
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dibr
omoa
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none
z 2-
Am
ino-
4-( 5
-nitr
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fury
l)th
iazo
lez
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min
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nitr
ophe
noly
11-A
min
ound
ecan
oic
acid
y o-
Ani
sidi
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Clz
Ari
stol
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cac
ids
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msa
lt( 7
7A
AI
21
AA
II)
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Bis
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mom
ethy
l)-1
3-p
ropa
nedi
olt
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ical
grad
ez C
Id
ispe
rse
blue
1y N
-But
yl-N
-(4-
hydr
oxyb
utyl
) nitr
osam
ine
4-C
hlor
o-o-
phen
ylen
edia
min
ez m
-Cre
sidi
ney
p-C
resi
dine
z C
yclo
phos
pham
idez
Die
thyl
ene
glyc
olD
imet
hyla
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icac
idy
Fose
tylA
lIQ
HC
lM
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etat
ez M
elam
iney
2-M
etho
xy-3
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inod
iben
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ran
2-N
apht
hyla
min
ez N
itril
otri
acet
icac
idz
Nitr
ilot
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acid
tri
sodi
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ltm
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ydra
tey
N-[
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ro-2
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yl) -
2-th
iazo
lyl]
form
amid
ez o-
Nitr
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sole
z N
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N-m
ethy
l-N
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ecyl
amin
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ethy
l-N
-tet
rade
cyla
min
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ethy
ldec
ylam
ine
N-N
itros
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opyl
) am
ine
Nitr
osod
ibut
ylam
inez
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itro
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phen
ylam
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itros
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uene
N-O
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lene
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carb
amyl
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xydi
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lene
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ide
Phe
nace
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Phen
azon
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Phen
ylph
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dium
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Phen
ylph
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y P
otas
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ate
Purp
urin
Que
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iny
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oxim
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rin
sodi
umy
Sali
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inez
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luen
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Tolu
idin
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Clz
Trp
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acet
atez
Ura
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Ute
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Ham
ster
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ethy
lhyd
roxy
ethy
lure
aM
ouse
12B
rom
oeth
anez
Chl
oroe
than
ey D
acar
bazi
nez
12-
Dic
hlor
oeth
anez
Die
thyl
stil
best
rolz
Eth
ylen
eox
idez
Gly
cido
lz ( N
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hyln
itros
o)ad
enos
ine
Proc
arba
zine
HC
lz 1
23-
Tri
chlo
ropr
opan
ez T
rim
ethy
lpho
spha
tey
Vin
ylac
etat
ez
Rat
26A
cryl
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Ally
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rea
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min
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ethy
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rez
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myl
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itros
oure
aA
traz
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CI
dir
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lue
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rom
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ptin
em
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N-n
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yl-N
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roso
urea
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cium
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roat
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apta
nz 2-
Chl
oro-
11
1-tr
iuo
roet
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Dac
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zine
z D
amin
ozid
ez 3
3-D
imet
hoxy
benz
idin
e-4
4-d
iisoc
yana
tey
33
-Dim
etho
xybe
nzid
ine
2HC
lD
imet
hyla
min
oeth
ylni
tros
oeth
ylur
ean
itri
tesa
lt1-
Eth
ylni
tros
o-3-
( 2-h
ydro
xyet
hyl)
-ure
a1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
N-H
exyl
nitr
osou
rea
ICR
F-1
59z
Isop
hosp
ham
idez
15-
Nap
htha
lene
diam
inez
Nit
robe
nzen
ez N
orle
stri
nz 4
4-T
hiod
iani
linez
Vin
ylac
etat
ez
Vag
ina
Mou
se1
AZ
Tz
Rat
2A
ZT
z N
-n-B
utyl
-N-n
itro
sour
ea( C
ontin
ued
onne
xtpa
ge)
647
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Vas
cula
rsy
stem
Ham
ster
91
2-D
imet
hylh
ydra
zine
2H
Cl
Gly
cido
lz H
exac
hlor
oben
zene
z N
-Nit
roso
-eth
yl-2
-oxo
prop
ylur
eaN
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aN
-Nitr
oso-
oxop
ropy
lchl
oroe
thyl
urea
N-N
itro
so-o
xopr
opyl
urea
N-N
itros
o-2-
phen
ylet
hylu
rea
Vin
ylch
lori
dez
Mou
se59
A-a
-CN
-Ace
tyl-
4-( h
ydro
xym
ethy
l)ph
enyl
hydr
azin
e1-
Ace
tyl-
2-ph
enyl
hydr
azin
eA
llyl
hydr
azin
eH
Cl
Are
colin
eH
Cl
Aza
thio
prin
eB
enzi
dine
2H
Cl
2-B
iphe
nyla
min
eH
Cly
13-
But
adie
nez
Cap
tafo
lz C
arba
myl
hydr
azin
eH
Cl
4-C
hlor
o-4
-am
inod
iphe
nyle
ther
z 1-
Chl
oro-
4-ni
trob
enze
ney
5-C
hlor
o-o-
tolu
idin
ey 4-
Chl
oro-
o-to
luid
ine
HC
ly p-
Chl
oroa
nilin
eH
Clz
Chl
orop
rene
z C
upfe
rron
z D
acar
bazi
nez
Dam
inoz
idez
24-
Dia
min
otol
uene
2H
Clz
12-
Dib
rom
oeth
anez
Dif
talo
ne7
12-
Dim
ethy
lben
z(a)
anth
race
ne1
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
N-E
thyl
-N-f
orm
ylhy
draz
ine
Eth
ylhy
draz
ine
HC
lG
lu-P
-1z
Glu
-P-2
z p-
Hyd
razi
nobe
nzoi
cac
idH
Cl
1-H
ydro
xysa
frol
ez Is
opre
neM
eA-a
-Cac
etat
ez N
-Met
hyl-
N-f
orm
ylhy
draz
ine
2-M
ethy
l-1-
nitr
oant
hraq
uino
nez
Mic
hler
rsquoske
tone
z 5-
Nitr
o-o-
tolu
idin
ey N
itro
fenz
N-N
itros
o-N
-met
hylu
reaz
Pent
achl
oroa
niso
lez
23
45
6-Pe
ntac
hlor
ophe
nol(
Dow
icid
eE
C-7
)y2
34
56
-Pen
tach
loro
phen
olt
echn
ical
grad
ez n-
Pen
tylh
ydra
zine
HC
lPh
enyl
ethy
lhyd
razi
nesu
lfat
ePh
enyl
hydr
azin
eH
Cl
Ster
igm
atoc
ysti
nz Te
tra
uoro
ethy
lene
z To
luen
edi
isoc
yana
tec
omm
erci
algr
ade
( 24
( 80
) -an
d2
6( 2
0) -
)zo
-Tol
uidi
neH
Clz
24
6-T
rich
loro
anil
iney
24
5-T
rim
ethy
lani
line
HC
lz 2
46-
Tri
met
hyla
nili
neH
Clz
Ure
than
ez V
inyl
carb
amat
eV
inyl
chlo
ride
z V
inyl
uor
idez
Vin
ylid
ene
chlo
ride
y 2
5-X
ylid
ine
HC
lz
Mon
key
2A
ato
xin
B1y
Ure
than
ez
Rat
32A
nilin
eH
Cly
Azo
benz
eney
Ben
zene
z C
livor
ine
Cup
ferr
onz
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
Z-E
thyl
-ON
N-a
zoxy
etha
neZ
-Eth
yl-O
NN
-azo
xym
etha
neI
QH
Cl
Las
ioca
rpin
e4
4-M
ethy
lene
-bis
( 2-c
hlor
oani
line)
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
N-N
itros
o-( 2
-hyd
roxy
prop
yl) -
( 2-h
ydro
xyet
hyl)
amin
eN
itro
so-1
23
6-t
etra
hydr
opyr
idin
eN
-Nitr
osob
is( 2
-oxo
prop
yl) a
min
eN
-Nit
roso
diet
hano
lam
ine
N-N
itro
sodi
ethy
lam
ine
N-N
itros
odim
ethy
lam
inez
N-N
itros
omet
hyl-
( 2-t
osyl
oxye
thyl
) am
ine
N-N
itros
omor
phol
ine
N-N
itro
sopy
rrol
idin
ez Pe
tasi
teni
neS
teri
gmat
ocys
tinz
Sym
phyt
ine
Tetr
auo
roet
hyle
nez
o-To
luid
ine
HC
lz T
rp-P
-2ac
etat
ez V
inyl
brom
ide
Vin
ylch
lori
dez
Vin
yl
uori
dez
aT
here
was
nore
port
edta
rget
site
in1
spec
ies
( rat
sor
mic
e)fo
r5
chem
ical
sw
ithsu
pers
crip
tsb
utth
ech
emic
alw
asev
alua
ted
byth
epu
blis
hed
auth
oras
aca
rcin
ogen
ald
rinz
diel
drin
z N
-nit
roso
pyrr
olid
inez
23
45
6-pe
ntac
hlor
ophe
nol
( Dow
icid
eE
C-7
)ya
ndur
etha
nez
bN
asal
cavi
tyin
clud
estis
sues
ofth
eno
sen
asal
turb
inat
esp
aran
asal
sinu
ses
and
trac
hea
c Ora
lcav
ityin
clud
estis
sues
ofth
em
outh
oro
phar
ynx
phar
ynx
and
lary
nx
Ach
emic
alis
liste
dun
der
each
orga
nev
alua
ted
aspo
sitiv
ein
anex
peri
men
tin
that
spec
ies
byat
leas
t1au
thor
The
refo
rea
chem
ical
may
beli
sted
unde
rse
vera
ltar
geto
rgan
san
dev
ery
chem
ical
liste
din
the
tabl
eis
posi
tive
inat
leas
t1sp
ecie
sIn
orde
rto
com
pare
resu
ltsin
rats
and
mic
esy
mbo
lsfo
llow
chem
ical
ste
sted
inbo
thsp
ecie
sa
zin
dica
tes
that
the
chem
ical
ispo
sitiv
eat
som
esi
tein
both
spec
ies
and
ay
indi
cate
sth
atit
was
test
edin
both
butp
ositi
vein
only
1a
Nth
enu
mbe
rof
chem
ical
sw
ithat
leas
t1po
sitiv
ete
stat
that
site
inth
atsp
ecie
sB
ecau
sem
any
chem
ical
sin
duce
tum
ors
atm
ore
than
1si
tein
agi
ven
spec
ies
man
ych
emic
als
appe
arm
ore
than
once
inth
eta
ble
648
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649
species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters
RESULTS IN RATS AND MICE
For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens
TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database
Chemicals evaluated as carcinogenic in
Rats Mice
All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)
Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2
a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not
b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats
All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical
to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included
The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site
Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common
650 GOLD ET AL TOXICOLOGIC PATHOLOGY
TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)
Target site Agent mixture or industrial process
Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e
Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke
Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products
Brain Vinyl chloride a
Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e
Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena
Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system
Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as
a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell
lymphotropic virus type I (HTLV-I) Vinyl chloridea
Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production
Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)
Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea
Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea
Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)
Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea
Mesenchymal tumors Azathioprinea
Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust
Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust
Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid
(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke
Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production
8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots
Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e
Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays
IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD
IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no
tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance
is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651
sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites
Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to
be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)
Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)
Target Organs of Human CarcinogensTo complement the compendium of target organs in car-
cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke
In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)
Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens
Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from
bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)
ACKNOWLEDGMENTS
We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention
REFERENCES
1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56
2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600
3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998
4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685
5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404
6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605
7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246
8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100
9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash
23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC
11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the
652 GOLD ET AL TOXICOLOGIC PATHOLOGY
US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240
12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute
13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program
14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX
15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11
16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash
34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c
Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729
Subc
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eous
Mou
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mom
ethy
l)-1
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nedi
olt
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ical
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ical
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and
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mom
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ical
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Met
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y H
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Die
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44
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iline
z C
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Rat
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cryl
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Am
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Bro
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ium
z C
hlor
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126
0ch
lori
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Chl
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rene
z 2
4-D
iam
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ez N
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1-E
thyl
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Eth
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Mal
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Met
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4-M
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l)be
nzen
amin
ez 4
4-M
ethy
lene
dian
iline
2H
Clz
Mir
exp
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ropy
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ine
44
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iline
z Pr
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37
8-Te
trac
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nz 4
4-T
hiod
iani
linez
Thi
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Tri
met
hylt
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Vin
ylac
etat
ez Z
inc
dim
ethy
ldith
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rbam
atez
Uri
nary
blad
der
Dog
23
3-D
ichl
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dine
44
-Met
hyle
ne-b
is( 2
-chl
oroa
nilin
e)H
amst
er3
Form
icac
id2-
[ 4-(
5-ni
tro-
2-fu
ryl)
-2-t
hiaz
olyl
] hyd
razi
dez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
acet
amid
eN
-[4-
( 5-N
itro-
2-fu
ryl)
-2-t
hiaz
olyl
] for
mam
idez
Mou
se12
2-A
cety
lam
ino
uore
nez
4-A
min
odip
heny
l2-
Am
inod
iphe
nyle
neox
ide
o-A
nisi
dine
HC
lz 4-
Chl
oro-
4-a
min
odip
heny
leth
erz
p-C
resi
dine
z 4-
Eth
ylsu
lpho
nyln
apht
hale
ne-1
-sul
fona
mid
eN
-Hyd
roxy
-2-a
cety
lam
ino
uore
nez
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez P
hena
cetin
z Te
lone
IIt
echn
ical
grad
ez U
raci
lz
Mon
key
12-
Nap
hthy
lam
inez
Rat
49A
ceta
min
ophe
nz A
llyli
soth
iocy
anat
ey 1-
Am
ino-
24-
dibr
omoa
nthr
aqui
none
z 2-
Am
ino-
4-( 5
-nitr
o-2-
fury
l)th
iazo
lez
4-A
min
o-2-
nitr
ophe
noly
11-A
min
ound
ecan
oic
acid
y o-
Ani
sidi
neH
Clz
Ari
stol
ochi
cac
ids
odiu
msa
lt( 7
7A
AI
21
AA
II)
22-
Bis
( bro
mom
ethy
l)-1
3-p
ropa
nedi
olt
echn
ical
grad
ez C
Id
ispe
rse
blue
1y N
-But
yl-N
-(4-
hydr
oxyb
utyl
) nitr
osam
ine
4-C
hlor
o-o-
phen
ylen
edia
min
ez m
-Cre
sidi
ney
p-C
resi
dine
z C
yclo
phos
pham
idez
Die
thyl
ene
glyc
olD
imet
hyla
rsin
icac
idy
Fose
tylA
lIQ
HC
lM
eA-a
-Cac
etat
ez M
elam
iney
2-M
etho
xy-3
-am
inod
iben
zofu
ran
2-N
apht
hyla
min
ez N
itril
otri
acet
icac
idz
Nitr
ilot
riac
etic
acid
tri
sodi
umsa
ltm
onoh
ydra
tey
N-[
4-( 5
-Nit
ro-2
-fur
yl) -
2-th
iazo
lyl]
form
amid
ez o-
Nitr
oani
sole
z N
-Nitr
oso-
N-m
ethy
l-N
-dod
ecyl
amin
eN
-Nitr
oso-
N-m
ethy
l-N
-tet
rade
cyla
min
eN
-Nit
roso
-N-m
ethy
ldec
ylam
ine
N-N
itros
obis
( 2-o
xopr
opyl
) am
ine
Nitr
osod
ibut
ylam
inez
N-N
itro
sodi
phen
ylam
iney
o-N
itros
otol
uene
N-O
xydi
ethy
lene
thio
carb
amyl
-N-o
xydi
ethy
lene
sulf
enam
ide
Phe
nace
tinz
Phen
azon
eo-
Phen
ylph
enat
eso
dium
y o-
Phen
ylph
enol
y P
otas
sium
bica
rbon
ate
Purp
urin
Que
rcet
iny
p-Q
uino
nedi
oxim
ey Sa
ccha
rin
sodi
umy
Sali
cyla
zosu
lfap
yrid
inez
o-To
luen
esul
fona
mid
eo-
Tolu
idin
eH
Clz
Trp
-P-2
acet
atez
Ura
cilz
Ute
rus
Ham
ster
1N
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aM
ouse
12B
rom
oeth
anez
Chl
oroe
than
ey D
acar
bazi
nez
12-
Dic
hlor
oeth
anez
Die
thyl
stil
best
rolz
Eth
ylen
eox
idez
Gly
cido
lz ( N
-6) -
( Met
hyln
itros
o)ad
enos
ine
Proc
arba
zine
HC
lz 1
23-
Tri
chlo
ropr
opan
ez T
rim
ethy
lpho
spha
tey
Vin
ylac
etat
ez
Rat
26A
cryl
amid
e1-
Ally
l-1-
nitr
osou
rea
3-A
min
o-9-
ethy
lcar
bazo
lem
ixtu
rez
1-A
myl
-1-n
itros
oure
aA
traz
iney
CI
dir
ectb
lue
15B
rom
ocri
ptin
em
esyl
atey
N-n
-But
yl-N
-nit
roso
urea
Cal
cium
valp
roat
eC
apta
nz 2-
Chl
oro-
11
1-tr
iuo
roet
hane
Dac
arba
zine
z D
amin
ozid
ez 3
3-D
imet
hoxy
benz
idin
e-4
4-d
iisoc
yana
tey
33
-Dim
etho
xybe
nzid
ine
2HC
lD
imet
hyla
min
oeth
ylni
tros
oeth
ylur
ean
itri
tesa
lt1-
Eth
ylni
tros
o-3-
( 2-h
ydro
xyet
hyl)
-ure
a1-
Eth
ylni
tros
o-3-
( 2-o
xopr
opyl
) -ur
ea
N-H
exyl
nitr
osou
rea
ICR
F-1
59z
Isop
hosp
ham
idez
15-
Nap
htha
lene
diam
inez
Nit
robe
nzen
ez N
orle
stri
nz 4
4-T
hiod
iani
linez
Vin
ylac
etat
ez
Vag
ina
Mou
se1
AZ
Tz
Rat
2A
ZT
z N
-n-B
utyl
-N-n
itro
sour
ea( C
ontin
ued
onne
xtpa
ge)
647
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Vas
cula
rsy
stem
Ham
ster
91
2-D
imet
hylh
ydra
zine
2H
Cl
Gly
cido
lz H
exac
hlor
oben
zene
z N
-Nit
roso
-eth
yl-2
-oxo
prop
ylur
eaN
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aN
-Nitr
oso-
oxop
ropy
lchl
oroe
thyl
urea
N-N
itro
so-o
xopr
opyl
urea
N-N
itros
o-2-
phen
ylet
hylu
rea
Vin
ylch
lori
dez
Mou
se59
A-a
-CN
-Ace
tyl-
4-( h
ydro
xym
ethy
l)ph
enyl
hydr
azin
e1-
Ace
tyl-
2-ph
enyl
hydr
azin
eA
llyl
hydr
azin
eH
Cl
Are
colin
eH
Cl
Aza
thio
prin
eB
enzi
dine
2H
Cl
2-B
iphe
nyla
min
eH
Cly
13-
But
adie
nez
Cap
tafo
lz C
arba
myl
hydr
azin
eH
Cl
4-C
hlor
o-4
-am
inod
iphe
nyle
ther
z 1-
Chl
oro-
4-ni
trob
enze
ney
5-C
hlor
o-o-
tolu
idin
ey 4-
Chl
oro-
o-to
luid
ine
HC
ly p-
Chl
oroa
nilin
eH
Clz
Chl
orop
rene
z C
upfe
rron
z D
acar
bazi
nez
Dam
inoz
idez
24-
Dia
min
otol
uene
2H
Clz
12-
Dib
rom
oeth
anez
Dif
talo
ne7
12-
Dim
ethy
lben
z(a)
anth
race
ne1
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
N-E
thyl
-N-f
orm
ylhy
draz
ine
Eth
ylhy
draz
ine
HC
lG
lu-P
-1z
Glu
-P-2
z p-
Hyd
razi
nobe
nzoi
cac
idH
Cl
1-H
ydro
xysa
frol
ez Is
opre
neM
eA-a
-Cac
etat
ez N
-Met
hyl-
N-f
orm
ylhy
draz
ine
2-M
ethy
l-1-
nitr
oant
hraq
uino
nez
Mic
hler
rsquoske
tone
z 5-
Nitr
o-o-
tolu
idin
ey N
itro
fenz
N-N
itros
o-N
-met
hylu
reaz
Pent
achl
oroa
niso
lez
23
45
6-Pe
ntac
hlor
ophe
nol(
Dow
icid
eE
C-7
)y2
34
56
-Pen
tach
loro
phen
olt
echn
ical
grad
ez n-
Pen
tylh
ydra
zine
HC
lPh
enyl
ethy
lhyd
razi
nesu
lfat
ePh
enyl
hydr
azin
eH
Cl
Ster
igm
atoc
ysti
nz Te
tra
uoro
ethy
lene
z To
luen
edi
isoc
yana
tec
omm
erci
algr
ade
( 24
( 80
) -an
d2
6( 2
0) -
)zo
-Tol
uidi
neH
Clz
24
6-T
rich
loro
anil
iney
24
5-T
rim
ethy
lani
line
HC
lz 2
46-
Tri
met
hyla
nili
neH
Clz
Ure
than
ez V
inyl
carb
amat
eV
inyl
chlo
ride
z V
inyl
uor
idez
Vin
ylid
ene
chlo
ride
y 2
5-X
ylid
ine
HC
lz
Mon
key
2A
ato
xin
B1y
Ure
than
ez
Rat
32A
nilin
eH
Cly
Azo
benz
eney
Ben
zene
z C
livor
ine
Cup
ferr
onz
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
Z-E
thyl
-ON
N-a
zoxy
etha
neZ
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yl-O
NN
-azo
xym
etha
neI
QH
Cl
Las
ioca
rpin
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4-M
ethy
lene
-bis
( 2-c
hlor
oani
line)
N-[
5-( 5
-Nit
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yl) -
13
4-th
iadi
azol
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l] ace
tam
idez
N-N
itros
o-( 2
-hyd
roxy
prop
yl) -
( 2-h
ydro
xyet
hyl)
amin
eN
itro
so-1
23
6-t
etra
hydr
opyr
idin
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-Nitr
osob
is( 2
-oxo
prop
yl) a
min
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roso
diet
hano
lam
ine
N-N
itro
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ine
N-N
itros
odim
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lam
inez
N-N
itros
omet
hyl-
( 2-t
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oxye
thyl
) am
ine
N-N
itros
omor
phol
ine
N-N
itro
sopy
rrol
idin
ez Pe
tasi
teni
neS
teri
gmat
ocys
tinz
Sym
phyt
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Tetr
auo
roet
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nez
o-To
luid
ine
HC
lz T
rp-P
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etat
ez V
inyl
brom
ide
Vin
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dez
Vin
yl
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aT
here
was
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port
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ies
( rat
sor
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chem
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emic
alw
asev
alua
ted
byth
epu
blis
hed
auth
oras
aca
rcin
ogen
ald
rinz
diel
drin
z N
-nit
roso
pyrr
olid
inez
23
45
6-pe
ntac
hlor
ophe
nol
( Dow
icid
eE
C-7
)ya
ndur
etha
nez
bN
asal
cavi
tyin
clud
estis
sues
ofth
eno
sen
asal
turb
inat
esp
aran
asal
sinu
ses
and
trac
hea
c Ora
lcav
ityin
clud
estis
sues
ofth
em
outh
oro
phar
ynx
phar
ynx
and
lary
nx
Ach
emic
alis
liste
dun
der
each
orga
nev
alua
ted
aspo
sitiv
ein
anex
peri
men
tin
that
spec
ies
byat
leas
t1au
thor
The
refo
rea
chem
ical
may
beli
sted
unde
rse
vera
ltar
geto
rgan
san
dev
ery
chem
ical
liste
din
the
tabl
eis
posi
tive
inat
leas
t1sp
ecie
sIn
orde
rto
com
pare
resu
ltsin
rats
and
mic
esy
mbo
lsfo
llow
chem
ical
ste
sted
inbo
thsp
ecie
sa
zin
dica
tes
that
the
chem
ical
ispo
sitiv
eat
som
esi
tein
both
spec
ies
and
ay
indi
cate
sth
atit
was
test
edin
both
butp
ositi
vein
only
1a
Nth
enu
mbe
rof
chem
ical
sw
ithat
leas
t1po
sitiv
ete
stat
that
site
inth
atsp
ecie
sB
ecau
sem
any
chem
ical
sin
duce
tum
ors
atm
ore
than
1si
tein
agi
ven
spec
ies
man
ych
emic
als
appe
arm
ore
than
once
inth
eta
ble
648
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649
species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters
RESULTS IN RATS AND MICE
For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens
TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database
Chemicals evaluated as carcinogenic in
Rats Mice
All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)
Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2
a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not
b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats
All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical
to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included
The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site
Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common
650 GOLD ET AL TOXICOLOGIC PATHOLOGY
TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)
Target site Agent mixture or industrial process
Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e
Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke
Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products
Brain Vinyl chloride a
Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e
Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena
Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system
Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as
a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell
lymphotropic virus type I (HTLV-I) Vinyl chloridea
Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production
Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)
Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea
Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea
Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)
Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea
Mesenchymal tumors Azathioprinea
Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust
Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust
Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid
(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke
Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production
8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots
Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e
Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays
IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD
IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no
tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance
is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651
sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites
Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to
be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)
Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)
Target Organs of Human CarcinogensTo complement the compendium of target organs in car-
cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke
In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)
Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens
Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from
bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)
ACKNOWLEDGMENTS
We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention
REFERENCES
1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56
2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600
3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998
4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685
5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404
6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605
7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246
8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100
9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash
23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC
11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the
652 GOLD ET AL TOXICOLOGIC PATHOLOGY
US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240
12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute
13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program
14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX
15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11
16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash
34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c
Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729
TAB
LE
1mdash
Sum
mar
yof
Car
cino
geni
cPo
tenc
yD
atab
ase
byta
rget
orga
n( C
onti
nued
)
Targ
etsi
teSp
ecie
sN
Che
mic
als
that
indu
cetu
mor
sat
each
site
Vas
cula
rsy
stem
Ham
ster
91
2-D
imet
hylh
ydra
zine
2H
Cl
Gly
cido
lz H
exac
hlor
oben
zene
z N
-Nit
roso
-eth
yl-2
-oxo
prop
ylur
eaN
-Nitr
oso-
ethy
lhyd
roxy
ethy
lure
aN
-Nitr
oso-
oxop
ropy
lchl
oroe
thyl
urea
N-N
itro
so-o
xopr
opyl
urea
N-N
itros
o-2-
phen
ylet
hylu
rea
Vin
ylch
lori
dez
Mou
se59
A-a
-CN
-Ace
tyl-
4-( h
ydro
xym
ethy
l)ph
enyl
hydr
azin
e1-
Ace
tyl-
2-ph
enyl
hydr
azin
eA
llyl
hydr
azin
eH
Cl
Are
colin
eH
Cl
Aza
thio
prin
eB
enzi
dine
2H
Cl
2-B
iphe
nyla
min
eH
Cly
13-
But
adie
nez
Cap
tafo
lz C
arba
myl
hydr
azin
eH
Cl
4-C
hlor
o-4
-am
inod
iphe
nyle
ther
z 1-
Chl
oro-
4-ni
trob
enze
ney
5-C
hlor
o-o-
tolu
idin
ey 4-
Chl
oro-
o-to
luid
ine
HC
ly p-
Chl
oroa
nilin
eH
Clz
Chl
orop
rene
z C
upfe
rron
z D
acar
bazi
nez
Dam
inoz
idez
24-
Dia
min
otol
uene
2H
Clz
12-
Dib
rom
oeth
anez
Dif
talo
ne7
12-
Dim
ethy
lben
z(a)
anth
race
ne1
1-D
imet
hylh
ydra
zine
y 1
2-D
imet
hylh
ydra
zine
2H
Cl
N-E
thyl
-N-f
orm
ylhy
draz
ine
Eth
ylhy
draz
ine
HC
lG
lu-P
-1z
Glu
-P-2
z p-
Hyd
razi
nobe
nzoi
cac
idH
Cl
1-H
ydro
xysa
frol
ez Is
opre
neM
eA-a
-Cac
etat
ez N
-Met
hyl-
N-f
orm
ylhy
draz
ine
2-M
ethy
l-1-
nitr
oant
hraq
uino
nez
Mic
hler
rsquoske
tone
z 5-
Nitr
o-o-
tolu
idin
ey N
itro
fenz
N-N
itros
o-N
-met
hylu
reaz
Pent
achl
oroa
niso
lez
23
45
6-Pe
ntac
hlor
ophe
nol(
Dow
icid
eE
C-7
)y2
34
56
-Pen
tach
loro
phen
olt
echn
ical
grad
ez n-
Pen
tylh
ydra
zine
HC
lPh
enyl
ethy
lhyd
razi
nesu
lfat
ePh
enyl
hydr
azin
eH
Cl
Ster
igm
atoc
ysti
nz Te
tra
uoro
ethy
lene
z To
luen
edi
isoc
yana
tec
omm
erci
algr
ade
( 24
( 80
) -an
d2
6( 2
0) -
)zo
-Tol
uidi
neH
Clz
24
6-T
rich
loro
anil
iney
24
5-T
rim
ethy
lani
line
HC
lz 2
46-
Tri
met
hyla
nili
neH
Clz
Ure
than
ez V
inyl
carb
amat
eV
inyl
chlo
ride
z V
inyl
uor
idez
Vin
ylid
ene
chlo
ride
y 2
5-X
ylid
ine
HC
lz
Mon
key
2A
ato
xin
B1y
Ure
than
ez
Rat
32A
nilin
eH
Cly
Azo
benz
eney
Ben
zene
z C
livor
ine
Cup
ferr
onz
12-
Dib
rom
oeth
anez
12-
Dic
hlor
oeth
anez
46-
Dim
ethy
l-2-
( 5-n
itro-
2-fu
ryl)
pyri
mid
ine
Z-E
thyl
-ON
N-a
zoxy
etha
neZ
-Eth
yl-O
NN
-azo
xym
etha
neI
QH
Cl
Las
ioca
rpin
e4
4-M
ethy
lene
-bis
( 2-c
hlor
oani
line)
N-[
5-( 5
-Nit
ro-2
-fur
yl) -
13
4-th
iadi
azol
-2-y
l] ace
tam
idez
N-N
itros
o-( 2
-hyd
roxy
prop
yl) -
( 2-h
ydro
xyet
hyl)
amin
eN
itro
so-1
23
6-t
etra
hydr
opyr
idin
eN
-Nitr
osob
is( 2
-oxo
prop
yl) a
min
eN
-Nit
roso
diet
hano
lam
ine
N-N
itro
sodi
ethy
lam
ine
N-N
itros
odim
ethy
lam
inez
N-N
itros
omet
hyl-
( 2-t
osyl
oxye
thyl
) am
ine
N-N
itros
omor
phol
ine
N-N
itro
sopy
rrol
idin
ez Pe
tasi
teni
neS
teri
gmat
ocys
tinz
Sym
phyt
ine
Tetr
auo
roet
hyle
nez
o-To
luid
ine
HC
lz T
rp-P
-2ac
etat
ez V
inyl
brom
ide
Vin
ylch
lori
dez
Vin
yl
uori
dez
aT
here
was
nore
port
edta
rget
site
in1
spec
ies
( rat
sor
mic
e)fo
r5
chem
ical
sw
ithsu
pers
crip
tsb
utth
ech
emic
alw
asev
alua
ted
byth
epu
blis
hed
auth
oras
aca
rcin
ogen
ald
rinz
diel
drin
z N
-nit
roso
pyrr
olid
inez
23
45
6-pe
ntac
hlor
ophe
nol
( Dow
icid
eE
C-7
)ya
ndur
etha
nez
bN
asal
cavi
tyin
clud
estis
sues
ofth
eno
sen
asal
turb
inat
esp
aran
asal
sinu
ses
and
trac
hea
c Ora
lcav
ityin
clud
estis
sues
ofth
em
outh
oro
phar
ynx
phar
ynx
and
lary
nx
Ach
emic
alis
liste
dun
der
each
orga
nev
alua
ted
aspo
sitiv
ein
anex
peri
men
tin
that
spec
ies
byat
leas
t1au
thor
The
refo
rea
chem
ical
may
beli
sted
unde
rse
vera
ltar
geto
rgan
san
dev
ery
chem
ical
liste
din
the
tabl
eis
posi
tive
inat
leas
t1sp
ecie
sIn
orde
rto
com
pare
resu
ltsin
rats
and
mic
esy
mbo
lsfo
llow
chem
ical
ste
sted
inbo
thsp
ecie
sa
zin
dica
tes
that
the
chem
ical
ispo
sitiv
eat
som
esi
tein
both
spec
ies
and
ay
indi
cate
sth
atit
was
test
edin
both
butp
ositi
vein
only
1a
Nth
enu
mbe
rof
chem
ical
sw
ithat
leas
t1po
sitiv
ete
stat
that
site
inth
atsp
ecie
sB
ecau
sem
any
chem
ical
sin
duce
tum
ors
atm
ore
than
1si
tein
agi
ven
spec
ies
man
ych
emic
als
appe
arm
ore
than
once
inth
eta
ble
648
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649
species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters
RESULTS IN RATS AND MICE
For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens
TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database
Chemicals evaluated as carcinogenic in
Rats Mice
All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)
Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2
a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not
b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats
All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical
to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included
The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site
Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common
650 GOLD ET AL TOXICOLOGIC PATHOLOGY
TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)
Target site Agent mixture or industrial process
Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e
Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke
Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products
Brain Vinyl chloride a
Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e
Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena
Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system
Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as
a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell
lymphotropic virus type I (HTLV-I) Vinyl chloridea
Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production
Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)
Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea
Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea
Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)
Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea
Mesenchymal tumors Azathioprinea
Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust
Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust
Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid
(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke
Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production
8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots
Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e
Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays
IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD
IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no
tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance
is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651
sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites
Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to
be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)
Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)
Target Organs of Human CarcinogensTo complement the compendium of target organs in car-
cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke
In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)
Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens
Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from
bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)
ACKNOWLEDGMENTS
We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention
REFERENCES
1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56
2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600
3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998
4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685
5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404
6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605
7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246
8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100
9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash
23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC
11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the
652 GOLD ET AL TOXICOLOGIC PATHOLOGY
US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240
12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute
13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program
14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX
15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11
16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash
34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c
Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649
species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters
RESULTS IN RATS AND MICE
For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens
TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database
Chemicals evaluated as carcinogenic in
Rats Mice
All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)
Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2
a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not
b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats
All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical
to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included
The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site
Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common
650 GOLD ET AL TOXICOLOGIC PATHOLOGY
TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)
Target site Agent mixture or industrial process
Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e
Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke
Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products
Brain Vinyl chloride a
Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e
Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena
Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system
Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as
a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell
lymphotropic virus type I (HTLV-I) Vinyl chloridea
Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production
Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)
Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea
Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea
Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)
Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea
Mesenchymal tumors Azathioprinea
Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust
Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust
Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid
(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke
Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production
8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots
Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e
Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays
IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD
IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no
tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance
is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651
sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites
Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to
be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)
Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)
Target Organs of Human CarcinogensTo complement the compendium of target organs in car-
cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke
In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)
Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens
Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from
bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)
ACKNOWLEDGMENTS
We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention
REFERENCES
1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56
2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600
3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998
4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685
5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404
6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605
7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246
8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100
9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash
23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC
11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the
652 GOLD ET AL TOXICOLOGIC PATHOLOGY
US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240
12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute
13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program
14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX
15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11
16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash
34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c
Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729
650 GOLD ET AL TOXICOLOGIC PATHOLOGY
TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)
Target site Agent mixture or industrial process
Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e
Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke
Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products
Brain Vinyl chloride a
Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e
Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena
Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system
Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as
a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell
lymphotropic virus type I (HTLV-I) Vinyl chloridea
Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production
Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)
Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea
Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea
Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)
Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea
Mesenchymal tumors Azathioprinea
Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust
Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust
Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid
(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke
Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production
8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots
Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e
Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays
IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD
IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no
tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance
is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651
sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites
Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to
be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)
Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)
Target Organs of Human CarcinogensTo complement the compendium of target organs in car-
cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke
In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)
Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens
Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from
bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)
ACKNOWLEDGMENTS
We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention
REFERENCES
1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56
2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600
3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998
4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685
5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404
6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605
7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246
8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100
9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash
23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC
11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the
652 GOLD ET AL TOXICOLOGIC PATHOLOGY
US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240
12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute
13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program
14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX
15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11
16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash
34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c
Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729
Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651
sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites
Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to
be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)
Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)
Target Organs of Human CarcinogensTo complement the compendium of target organs in car-
cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke
In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)
Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens
Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from
bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)
ACKNOWLEDGMENTS
We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention
REFERENCES
1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56
2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600
3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998
4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685
5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404
6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605
7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246
8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100
9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash
23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC
11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the
652 GOLD ET AL TOXICOLOGIC PATHOLOGY
US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240
12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute
13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program
14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX
15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11
16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash
34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c
Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729
652 GOLD ET AL TOXICOLOGIC PATHOLOGY
US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240
12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute
13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program
14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX
15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11
16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash
34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c
Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729