G3ImE8w@ report no 94/51

This report is based on a paper given on behalf of the CONCAWE Health Management Group to the Workshop on the Carcinogenicity of Coal and Petroleum Derived Substances held a t the EC Joint Research Centre at lspra, Italy, May 25-26, 1992.

R.J. Ellison

B.J. Simpson Technical Coordinator

Reproduction permined with due acknowledgement

O CONCAWE Brussels February 1994

report no 94/51

ABSTRACT

Untreated lubricant base oils have been associated in the past with the development of human skin cancer To give a better understanding of these health effects, industry has conducted an extensive range of long-term dermal carcinogenicity studies with the objective of identifying the influence of different types of refinery processing and t o establish the important base oil compositional factors The studies have led t o improved refining techniques and t o the development of simple markers for control purposes based on a standard analytical test.

However, with the increasing emphasis on the regulatory classification and labelling of petroleum products, i t is proposed that the same markers can be effectively used for the classificatiorl of base oils.

The report describes the development of markers for the prediction of base oil carcinogenicity and examines the relative merits of t w o particular candidates, one based on dimethyl sulphoxide extraction by method IP 346 and the other based on benzo(a)pyrene (Bap) concentration.

KEYWORDS

Animal, aromatic extract, base oil, benzo(alpyrene, carcinogens, classification, dermal, DMSO extract, IP 346 test, ISPRA, labelling, lubricant base oils, marker, mice, PAC, RAE, skin, tumour.

NOTE Corrsiderable efforts have beerr made to assure the accuracy and reliabdiry of the information contained in tlhs publication However, rreitlier CONCA WE nor any conlpany participatirlg in CONCA WE can accept liabdity for any loss. damage or injury whatsoever resulting from the use of this information

This repot! does not necessarrly represent the views of any company particrpatrng in CONCA WE

(cxml~@w@ report no. 94/51

CONTENTS

1. INTRODUCTION

2. HEALTH ASPECTS OF MINERAL OlLS AND DEVELOPMENT OF CONTROL MEASURES

3. PETROLEUM SUBSTANCES AND THE IP 346 METHOD

3.1 PETROLEUM SUBSTANCES 3.2 LUBRICANT BASE OlLS AND PAC CONTENT 3.3 IP 346 METHOD 3.4 RESIDUAL AROMATIC EXTRACTS

4. CARClNOGENlClTY MARKERS

4.1 SUPPORTING EVIDENCE 4 2 TUMOUR INCIDENCE CONSIDERED SIGNIFICANT 4 3 INFLUENCE OF STRAIN OF MOUSE ON TUMOUR RESPONSF . 4.4 USE OF DATA FOR PREDICTING CARCINOGENIC POTENCY 4.5 DMSO EXTRACT AND BAP MARKERS 4.6 CONFIRMATORY STUDIES 4.6.1 Using basestock blends 4.6.2 Additional data

5 CONCLUSIONS

6 REFERENCES

Table 1

Figures 1 to 5

Appendix: Supporting data for the IP 346 DMSO marker

report no. 94/51

INTRODUCTION

llntreated lubricant base oils have been associated in the past with the development of human skin cancer. To give a better understanding of these health effects, industry has conducted an extensive range of long-term dermal carcinogenicity studies with the objective of identifying the influence of different types of refinery processing and to establish the important base oil compositional factors. The studies have led to improved refining techniques and to the development of simple markers for control purposes based on a standard analytical test.

However, with the increasing emphasis on the regulatory classification and labelling of petroleum products, it is proposed that the same markers can be effectively used for the classification of base oils.

The report describes the development of markers for the prediction of base oil carcinogenicity and examines the relative merits of two particular candidates, one based on dimethyl sulphoxide extraction by method IP 346 and the other on benzo1a)pyrene Bap) concentration.

Supporting experimental evidence for the study is a data base consisting of over one hundred skin painting studies conducted by CONCAWE member companies over a period of twenty years. This evidence is fully documented in the Appendix to the report.

The report is based on a paper given to the Workshop on the Carcinogenicity of Coal and Petroleum Derived Substances held at the EC Joint Research Centre at lspra, Italy, May 25-26, 1992.

report no. 94/51

HEALTH ASPECTS OF MINERAL OILS AND DEVELOPMENT OF CONTROL MEASURES

Reports in the literature dating back to the early 1920s indicate that the use of poorly or unrefined mineral oils under conditions of poor personal hygiene has been associated with skin cancer in man. 1 The subject has been extensively reviewed in the literature arid reference is made to the IARC study 7. and to the CONCAWE Dossier on Aromatic Extracts. 3

Since the discovery that refinery processirlg can irifluence the carcinogenic poteritial of lubricants, the oil industry has conducted a wide range of studies to identify the factors involved. This has been one reason for the introduction of more severe refining techniques, such as solvent refining and hydrotreatment, and it is flow possible to produce lubricating oils that are non-carcinogenic. As a result, older refining methods in Europe have been largely discontinued.

The standard procedure for assessing carcinogenic potential is by long-term animal skin painting studies. This involves applying test samples to the skin, several times a week for the major portion of the life span of the test animals. Such experiments may take two to three years to complete.

For industrial purposes, once the basic trends have been established, quicker alternative ways of assessing carcinogenic potential are advaritageous for routine use,. 4 There is also the need to minimize continual animal testing.

By the mid 1980s, a number of CONCAWE member companies had developed correlations between the results of animal studies and simple analytical parameters and were using such techniques for a variety of purposes. Recognising the importance of these developments, CONCAWE convened a multi-disciplinary study to review the subject. Member companies submitted data from their own records and altogether a data base of some 76 studies was established.

The conclusions of this work were reported to the EC in 1988. 5 CONCAWE recommerided that, in the absence of any appropriate long-term ariimal test data, the carcinogenicity of lubricant base oils and distillate aromatic extracts should be assessed based on the dimethyl sulphoxide (DMSOI extract as determined by the IP 346 method. All substarices with a DMSO extract of 3% (mlm) or greater should be considered as Class 2 carciriogens.

Subsequently, this proposal and the supporting experimental data have been reviewed by the TPC Working Group on the Classification and Labelling of Dangerous Substances, initially at the Working Group Meeting or1 25-26 May 1992 held at the EC Joint Research Centre, Ispra, and later at following meetings in Brussels.

With the voluntary acceptance of this standard by industry in many parts of the world, the report describes the supporting evidence for the recommendations.

The Appendix iricludes all the information known to CONCAWE at the end of 1992, including the studies published after the Ispra Workshop in the paper by Chasey and McKee. 6

report no. 9415 1

PETROLEUM SUBSTANCES AND THE IP 346 METHOD

PETROLEUM SUBSTANCES

Most petroleum substances come into the category described in the European Inventory of Existing Commercial Chemical Substances (EINECS) as "substances of unknown or variable composition". In the petroleum industry, such substances are usually manufactured t o meet specified physical and performance criteria, rather than a defined chemical composition. In consequence, the assessment of potential carcinogenicity can be difficult i f based solely on the definitions given in EINECS.

LUBRICANT BASE OILS AND PAC CONTENT

I t has been shown that the molecular species responsible for carcinogenic potential of lubricant base oils are principally the three t o seven ring polycyclic aromatic compounds (PACs). 1 in the simplest case, the aromatic rings may consist of only hydrogen and carbon atoms and these compounds are termed polycyclic aromatic hydrocarbons (PAH). More complex structures may contain nitrogen, sulphur or oxygen atoms and as the number of rings increases, the possible steric arrangements increase rapidly. The molecules may also have side-chains of varying lengths, structures and complexity; such compounds are referred to as alkylated PACs.

It has been shown that polycyclic aromatic C O ~ P O L J ~ ~ S can be selectively extracted from base oil streams by a dirnethyl sulphoxide (DMSO) solvent. 7 The oil industry has therefore used this approach for a procedure t o characterize the PAC content. A standard method for the extraction has been developed and is described in method IP 346. 8

IP 346 METHOD

The IP 346 method is a gravimetric procedure in which a sample of oil is diluted with cyclohexane and extracted twice with DMSO. The sample is cut so as to exclude material boiling below 300°C. The resulting extract includes the three t o seven ring polycyclic aromatic hydrocarbons in the test sample, but it is recognised that the method extracts other material as well. The resulting DMSO extract is therefore higher in percentage terms than the PAC content determined by a GLC analysis.

The IP 346 procedure is suitable for use with lubricant base oils and aromatic extracts from vacuum distillates, but it is not suitable for use with substances containing asphaltenes andlor resins such as some residual oils, residual fuels and bitumen. With such oils, the asphaltenic components prevent the separation of the DMSO extract.

In addition, the method is not suitable for use with used oils or formulated products containing additives. With these materials, the dimethyl sulphoxide may extract components from the additives as well as from the base oil, thus rendering the results inconclusive.

report no. 94/51

Experience has indicated that it is important to use a standardised method for determining the DMSO extract. The composition of the fraction obtained by DMSO extraction is dependent on the test procedure and different methods have been showr~ to give significantly different extract levels. For the correlations described later in this report, it is essential that only the IP 346 procedure is used.

RESIDUAL AROMATIC EXTRACTS

Typically, residual aromatic extracts have a boiling range from about 400°C to above 650°C. Because of the high boiling range, the molecules extracted by DMSO are likely to be highly alkylated or possess high molecular weight side chains and are therefore markedly different from those extracted from distillate aromatic extracts. There is little evidence to indicate that residual aromatic extracts are carcinogenic and, for this reason, it is not appropriate to base the classification on the DMSO extract. A high level of extract by IP 346 may not necessarily indicate potential carcinogenicity.

~ ~ ~ ~ ~ w @ report no. 94/51

CARCINOGENICITY MARKERS

SUPPORTING EVIDENCE

At the time of the presentation to the EC lspra Workshop in May 1992, the supporting data available for the evaluation of suitable markers consisted of some 76 skin painting studies. Most of this information was supplied to CONCAWE over the period 1981 to 1985 and came from individual studies conducted by member companies in the previous 15 to 20 years.

As these studies were conducted independently by member companies and did not form part of a co-ordinated programme, it was necessary to select appropriate samples from the information received that had the required manufacturing history, generic descriptions and analytical data. In particular, it was necessary to ensure that the DMSO extract had been determined by the IP 346 method, as other extraction procedures can give significantly different results.

The samples selected for the evaluation programme are listed in the Appendix. Table 1 gives a summary of the sample description, tumour incidence, DMSO extract and benzo(a)pyrene content, Table 2 lists details of test protocols and Table 3 lists the available analytical data on the test samples.

At the end of 1992, further information became available to CONCAWE with the publication of the paper by Chasey and McKee. 5 Some of the studies reported in this paper had already been included in the original CQNCAWE data base, but others studies were new. The additional new data are listed in Table 4 of the Appendix.

The presentation to the lspra Workshop in May 1992 was based on the information contained in Tables 1 to 3 of the Appendix. With the publication of the Chasey and McKee paper, the additional data listed in Table 4 has been used to confirm previous conclusions and to assess the accuracy with which potentially carcinogenic oils can be identified.

TUMOUR INCIDENCE CONSIDERED SIGNIFICANT.

For assessing the outcome of the dermal carcinogenicity studies, a sample has been considered as potentially carcinogenic if 4% or more of the test animals developed tumours. The 4% incidence rate was chosen as being above the typical background level for the untreated controls. For a typical study, this means that for a positive result, at least two of the 50 animals showed evidence of tumour formation.

Discussions in the TPC Classification and Labelling working group and with IARC have considered this 4% figure to be valid, although possibly severe.

INFLUENCE OF STRAIN OF MOlJSE ON TUMOUR RESPONSE

Information on the test protocols used by member companies is listed in Table 2 of the Appendix. This shows that member companies have used two different strains of mouse, the C3H variety and the CFI variety. It has been found that those studies conducted with the C3H mouse strain often gave a higher tumour response than those conducted with the CF1 mouse. This is illustrated in Figure 1 which shows tumour response against DMSO extract for each of the two strains. With the C3H mouse, tumour response rates in

report no. 94/51

excess of 70% can be obtained from samples with a DMSO extract in the 5 to 10% (mlm) range, whereas with the CF1 mouse, tumour response rates for similar samples are not in excess of 50%.

This finding adds a further degree of variability to the data base in addition to those of test procedure, test duration, dosage rates, etc. The marker levels discussed below have been developed on a worst case basis and the variability in the data base adds to the strength and applicability of the markers proposed.

4.4 USE OF DATA BASE FOR PREDICTING CARCINOGENIC POTENCY

The relationship between skin tumour formation and DMSO extract or Bap content are shown as scatter diagrams in Figures 1 to 3. These plots readily show the number of points above the passlfail limit of a 4% tumour incidence rate and give a simple graphical basis for setting passlfail limits for possible markers. However, because of the different protocols used in developing the data, such diagrams do not give a sound basis for developing mathematical relationships for the prediction of carcinogenic response (the number of animals expected to develop tumours on the basis of the measured DMSO extract).

4.5 DMSO EXTRACT AND BAP MARKERS

The relationship between tumour incidence and DMSO extract is shown in Figure 2. This scatter diagram illustrates that, with one exception, all of the 26 samples with a DMSO extract greater than 3% gave rise to significant skin tumour formation in animal studies. Only one sample with a DMSO extract of less than 3% was positive. This so-called "false negative" sample was CONCAWE Sample No. 90, a solvent-extracted oil.

The alternative marker studied was benzo(a)pyrene (Bap). Bap can be considered as representative of the polycyclic aromatic hydrocarbons found in lubricant base oils and it can be determined by a variety of techniques including gas chromatography and high-performance liquid chromatography. The Bap data in this paper have been determined by the method described by Grimmer 9. IARC 10 have reported that there is sufficient evidence to indicate that Bap is carcinogenic in animal studies.

However, the scatter diagram in Figure 3 shows that Bap content alone is not sufficient for accurately discriminating between potentially carcinogenic and non-carcinogenic lubricant base oils as there is no clear dividing line between potentially carcinogenic and non-carcinogenic oils; with Bap contents between 0.03 and 0.3 mglkg, test results could either be positive or negative.

Figure 4 shows that the correlation between DMSO extract and Bap content is poor.

4.6 CONFIRMATORY STUDIES

4.6.1 Using basestock blends

Six of the samples included in the above evaluations were blends of lubricating oil basestocks where long-term dermal carcinogenicity studies had been conducted on both the individual comporlents and the blends.

report no. 9415 1

Three of the blends, CONCAWE Samples 108, 109 and 110, were based on components that had given rise to a significant tumour response in the initial studies. These were then cut back with a non-carcinogenic white oil so as to give blends with calculated DMSO extract levels, two below 3% and one above 3%. Samples 108 and l09 with DMSO extracts below 3% did not give rise to any tumour formation on further testing, whereas Sample 110 with a DMSO extract of 6.3% resulted in 10% tumours.

CONCAWE Samples 106 and 107 were made up from constituents that had all previously tested negative and had DMSO extract levels of below 3%. Both of these blends tested negative.

The final blend, CONCAWE Sample 95, had a DMSO extract of 13% and tested positive.

These studies give further experimental support to the choice of 3% DMSO extract as the control level for the marker, although it is not proposed that the wse of the marker should be extended to cover such preparations.

4.6.2 Additional data

The additional data made available on the publication of the paper by Chasey and McKee 5 gave the opportunity of further checking and confirming the recommendations put to the lspra Workshop. Inclusion of the new data increased the number of studies available from 52 to 104. Figure 5 shows the new data superimposed on Figure 2.

On the basis of all the data available to CONCAWE at the end of 1992, the accuracy with which the DMSO marker can discriminate between potentially carcinogenic and non-carcinogenic base oils is quantified in Table 1. This shows predictability based on DMSO marker levels set at 1 %, 2% and 3%.

If the marker level is set at l%, the marker can predict the onset of tumorigenic activity, but i t is accompanied by an unacceptably high level of false-positives (16%). At 2%, one false negative is given in 104 samples and at 3%, three false negatives are given.

In view of the comments concerning the severity of the tumour incidence level considered positive by CONCAWE and the fact that two of the three false negatives only gave rise to a tumour incidence of 5%, i t is considered that a DMSO extract marker set at 3% gives a satisfactory limit for classification purposes.

report no. 94/51

CONCLUSIONS

CONCAWE considers that the use of a marker based on the dimethyl sulphoxide (DMSO) extract by method IP 346 offers a simple and effective system for the prediction of the carcinogenic potential for lubricant base oils and distillate aromatic extracts.

The scope of the IP 346 method does not allow the proposed marker to be applied to products containing asphaltenes, such as residual fuel oils, or to formulated products containing additives. Also, the marker is not applicable to gas oils or residual aromatic extracts.

The method by which the extract is determined must be IP 346, other analytical methods are likely to give different results and should not be used for classification purposes. The IP 346 procedure only requires equipment that is routinely available in a manufacturing location.

report no. 9415 1

REFERENCES

Medical Research Council (1 968) The carcinogenic action of mineral oil - a chemical and biological study. Special report series No 306. London: HMSO

IARC (1984) Monographs on the evaluation of the carcinogenic risk of chemicals to humans. Polynuclear aromatic hydrocarbons, Part 2, carbon blacks, mineral oils (lubricant base oils and derived products) and some nitroarenes. Vol 33, 87-168. Lyon: International Agency for Research on Cancer

CONCAWE (1 992) Aromatic Extracts. Product Dossier No 9211 01 Brussels: CONCAWE

Roy, T.A. et al (1988) Correlation of mutagenic and dermal carcinogenic activities of mineral oils with polycyclic aromatic compound content. Fund Applied Toxicol 446-4476

CONCAWE ( 1 988) Classification of aromatic extracts and petroleum distillates for Annex I of EEC Dangerous Substances Directive. Paper submitted to Dr. K. Krisor (DG XI) for discussion in The Dangerous Substances Directive TPC Working Group on 25th October. Brussels: CONCAWE

Chasey, K.L. and McKee, R.H. (1993) Evaluation of the dermal carcinogenicity of lubricant base oils by the mouse skin painting bioassay and other proposed methods. J Applied to xi col^ 57-65

Van der Wiel, A. (1993) Selective determination of potentially hazardous polycyclic aromatics in luboil fractions by the DMSO extraction method - As development, evaluation and use. Report AMER 93.023 (External version of internal KSLA report issued 1979). Shell Research B.V., KonIShell Lab. Amsterdam.

IP (1993) Determination of polycyclic aromatics in unused lubricating base oils and asphaltene free petroleum fractions - dimethyl sulphoxide extraction refractive index method. IP 346192. In: Standard methods for analysis and testing of petroleum and related products Vol 2. Chichester: John Wiley and Sons

Grimmer, G. et al (1981) Profile of the polycyclic aromatic hydrocarbons from lubricating oils. Inventory by GCIMS-PAH in Environmental Materials, Part l. Fresenius ZAnal Chem 306, 347-355

IARC (1983) Monographs on the evaluation of the carcinogenic risk of chemicals to humans. Polynuclear aromatic hydrocarbons, Part 1, Chemical, environmental and experimental data. Vol 32, 21 1-224. Lyon: international Agency for Research on Cancer

cxxW8w@ report no. 94/51

Table 1 : Accuracy of prediction using DMSO extract marker

Prediction

Correct positive predictions

Correct negative predictions,

False positive predictions

False negative predictions

DMSO extract marker level (% m/m)

1 % 2% 3 %

37 36 34

51 57 64

16 10 3

0 1 3

(cxmmBlw@ report no. 9415 1

% mice with tumours - CF1 mouse strain

% DMSO extract by IP 346 (mlm)

O h mice with tumours - C3N mouse strain

1 W

% DMSO extract by IP 346 (mlm)

Figure 1: Influence of strain of mouse on tumour response

( cxx iE~W@ report no. 94/51

% mice with tumors

% DMSO extract by IP 346 (mlm)

% mice with tumors

% DMSO extract by IP 346 (mlm)

Figure 2: Tumour formation as a function of DMSO extract by IP 346.

(LxNiG~w@ report no. 94/51

% mice with tumours

Y

*

*

ENLARGED BELOW

Y

*

Bap content (mglkg)

% mice with tumours

Bap content (mglkg)

Figure 3: Tumour formation as a function of Bap content

report no. 94/51

Bap Content (mglkg)

% DMSO extract by IP 346 (mlm)

Figure 4: Relationship between DMSO extract and Bap Content

txxiYmw@ report no. 94/51

mice with tumours 1W

SO

80

70

60

50

40

30

20 ENLARGED BELOW

10

0 0 5 10 15 20 25 30 35 40

% DMSO extract by IP 346 (mlm)

% mice with tumours

% DMSO extract by IP 346 (mlm)

A New data from paper by Chasey and McKee

* Original data

Figure 5: Tumour formation as a function of DMSO extract:

Addition of new data, February 1993.

report no. 94/51

APPENDIX

SUPPORTING DATA FOR THE lP346 DMSO MARKER

The tables listed below summarize the data submitted by member companies to CONCAWE as pan of its investigations into the relationship between the chemical composition of mineral oils and their ability to cause skin cancer in mice :

Table 1: Study data grouped according to refinery processing. The table includes relevant data received by CONCAWE up to 31 11 2/91.

Table 2: Summary of test protocols giving information concerning date of test, strain of mouse, dose, frequency of dosing and test duration for the studies listed in Table 1.

Table 3: Physical and chemical properties for the test, samples listed in Table 1.

Table 4: Study data received since 31/12/91 from the paper by Chasey and McKee.

The CONCAWE paper on the DMSO extract marker given in May 1992 to the lspra Workshop on the Carcinogenicity Classification of Complex Petroleum Substances was based on the information given in Tables 1, 2 and 3 only.

(cxmNmlw@ report no. 94/51

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report no. 94/51

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il

Da

te

Wa

n)

An

ima

l

Str

ain

N

o

CF

1 4

8

C3

H

30

CF

1 4

8

CF

l 5

0

CF

1 4

8

CF

1 5

0

C3

H

30

C3

H

30

C3

H

30

CF

1 4

8

C3

H

40

Dose

F

msu

ancy

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ura

tto

n

pl

ltim

edw

cekl

[N

ote

11

20

0

2

17

m

25

3

L

T

20

0

2

18

m

20

0

2

18

m

20

0

2

18

m

20

0

2

18

m

25

3

LT

25

3

LT

25

3

L

T

ZOO

2

1

8 m

25

3

L

T

18

m

COnGawe report no. 94/51

E E E E E m m , " D m 3

:: :: 8:::: N N N N N

CO

NC

AW

E m

iner

al o

il sk

in p

ain

ting

stu

dies

: S

ampl

e p

hvs

ica

l en

d c

hem

rcal

pro

pe

rlie

s

Tab

le 3

V

acu

um

dis

tilla

te [

raw

un

tre

ate

d o

r d

ew

axe

d o

niy

l

Ara

ma

t~c

Car

bon

(Bra

ndas

1 ID

%)

Rel

atw

e d

en

sltv

151

1 5O

C

K.

Vis

co

s~

w at

37

.8"C

lm

m2

lsl

K.

Vis

cost

ty a

t 98

.9O

C

lmrn

2/s

l S

ulph

ur c

on

ten

t 1%

mim

l

DM

SO

Ext

ract

: 1P

346

1% m

hl

D

MS

O E

xtra

ct:

Ref

.lnde

x/2S

0C

PC

A C

onte

nt

lmg

lkg

l F

luor

enth

ene

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ane

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vsan

e B

enzo

lbifl

uora

nthe

ne

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zo(s

ipvr

ene

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zo(a

tpvr

enrr

P

ervl

ene

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zolg

.h.~

)per

ylen

e 1

-2 B

enzo

fiuor

ena

2-3

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zoflu

oren

e B

enzo

(a1a

nthr

acan

a B

enza

lklfl

uora

ntha

ne

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en

oll.

2.3

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en

e

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enzo

anth

rsce

nes

C18

H1O

S

Fir

st ~

ssu

ed

: 12

-10

-32

R

av~

sed

: 1

0-0

2-9

3 R

avls

ed fo

rma

t

(!Xmmaw@ report no. 94/51

CO

NC

AW

E A

NA

LY

TIC

AL

DA

TA

BA

NK

Tab

le 3

S

olv

en

t-e

xtra

cte

d a

ils

Aro

rnat

tc C

arbo

n IB

ran

de

sI

1%)

Rel

ativ

e d

en

sw

l5

11

5°C

K.

Vis

co

sm

at

37.S

°C

lmrn

2Is

l K.

Vis

cosa

tv a

t 98

.9O

C

lmrn

2Is

l S

ulph

ur c

on

ten

t 1%

rn

lmi

OM

SO

Ext

ract

: P

34

6

1% r

nh

l O

MS

O E

xtra

ct:

Re

f.ln

de

~l2

5~

C

PC

A C

on

ten

t lr

ng

ikg

l F

luo

rsn

the

ne

P

vren

e C

hw

sen

a

Be

nro

lblf

luo

ran

the

ne

8

en

zole

lpvr

en

e

Be

nzo

lalp

vre

ne

P

ervl

ene

Ben

zolg

,h,il

perv

lene

1

-2 B

enzo

fluor

ene

2-3

Ben

zoflu

aren

e B

en

rala

lan

thra

cen

e

Be

nza

lklfl

uo

ran

the

ne

In

de

no

ll.2

.3)p

vre

ne

O

iben

zoan

thre

cene

s C

18

HlO

S

Fir

st ~

ssu

ed: 1

2-1

0-9

2

Re

v~se

d:

10

-02

-93

R

ewse

d fo

rma

t

CO

NC

AW

E A

NA

LY

TIC

AL

DA

TA

BA

NK

Tab

le 3

S

olv

en

tsxt

ract

ed

, e

art

h tr

ea

ted

4ro

mst

lc C

arbo

n IB

rand

esl

(%l

Ma

twe

den

stty

151

1 S

°C

<. V

isco

s~ty

at

37.S

°C

1rn

rn2

k)

<. Vis

cosi

ty a

t 9

8.9

"C

tmrn

21s)

ju

lph

ur

con

ten

t (%

mlr

n)

3MS

O E

xtrs

ct:

lP3

46

(%

mlrn

) 3

MS

0 E

xtra

ct:

Rs

f.ln

da

~l2

5~

C

>CA

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nte

nt

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gR

g)

Flu

oran

then

e P

yren

a C

hrys

ene

Ben

zo(b

1flu

oran

then

a B

enzo

ielp

yren

s B

snzo

ta)p

yren

e P

eryl

ene

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zolg

.h,i)

pery

lene

1

-2 B

enzo

fluor

ene

2-3

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zoflu

oren

e B

snzo

la)a

nthr

acsn

e B

enzo

(k1f

luor

anth

ene

Ind

en

o(l

,2,3

)pyr

en

a

Dib

enzo

anth

race

nes

C1

8H

IOS

Firs

t ess

usd:

1

2-1

0-9

2

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tsad

: 1

0-0

2-9

3

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(W2WiE~~@ report no. 94/51

" g ' ' m " 2 ; -.,-. r.' 0 . _ a I

m 2 in .. 2 ' 9 - m 2 ... 0 v

(LxI3m8w@ report no. 94/51

(!ZmiG@w@ report no. 94/51

(Ixml~8w@ report no. 94/51

(cXmKmW@ report no. 94/51

U U - - - - - - . - , - , *,...-,..,.. ' ? g o o ? - ' m * 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 v v v v v v v v v v v v o@@ .-.

(cimiW8w@ report no. 94/51

. c!

Y 2 7, 2 W C

m 0

... r. m m m ,

cxcxmmIw@ repon no. 94/51

Table 4: Summary of CONCAWE mineral oil skin painting data: Additional study data received since 31112191

Chssey 5 McKee Sample No.

Tumour response

Animals %T

DMSO extrect iP 346 % mlm

Vacuum distillates - raw untreated I

Solvent extracted distillates l

BoP Content Yeer of

m g k study

Solvent extracted end hydrotreated distillates

continued..

l

Crude

type .p

P P

P P P P P P P P P P P P P P P

P P P P P P P P P P P P P P P P P P P P

(!xHMmw@ report no. 94/51

hasey Tumour response McKee

ernpie No Animnis

ydrotraoted distillates

istiilote aromatic extract8 - untreated I

istiiiote aromatic extracts . hydrotreated

DMSO extracl IP 3 4 6 % mlm

dined vacuum residunis

Bap Content

m d k g

9 4

Year of study

0 50 0

Notes: Crude type P denotes paraffinic, N denotes naphthenic

First issued: 11-02-93