TAC IDNcxHSON TH

EVUATlOO OF TH c.INOGIC RISK

OF CHCA TO MA:

Asbestos

Voluræ 14

This publication represets the views of anIA WJrking Group on the

Evluation of the Carcinogenic Risk of Chemicals ta Nanwhich net in Lyon,14- 1 7 Decerr 1976

LAR llRKING GRUP ON TH EVTION OF TH c.Z\~nl(C P.ISK OF CHCATO MA: ASBES

Lyon, 14-17 Deemr 1976

M2rsDr G. Berr, M=cal Research Conncil Pneumoniosis Unit, Llandough

Hospi ta, Penth, Glairgan CF6 1X, UK

Professor J. Bignon, Service Hospitalo-Universitaire de Pneurlogie,Centre Hospitalier Inteootml, 40 Aveue de Verdnn,94010 Créteil, France

Professeur A.M. Lager, Assoiate Pro fe ssor , Mieralog, Monnt SinaiSchexÜ of Mecine of the City University of New York, FifthAvenue and lOOth Street, New York, NY 10029, USA

Dr R.A. Len, Schol of Pulic Health, University of Illinois at thM=cal Ceter, PO Box 6998, Chcago, Illinis 60680, USA

Dr F .D. Pooley, Depatrt of Mieral Exloitation, UniversityCollege, Nert Rad, Cardiff CF2 lTA, UK

Dr D.P. Rall, Director, National Institute of Enviroruntal HealthSciences, PO Box 12233, Research Triangle Park, NC 27709, USA(Chai rman)

Professor H.-W. Schlipköter, Direktor des ~alzinischen Instituts fürLufthygiene nnd Silikoseforschnng an der Universität DÜseldorf,Gulittstrasse 53, Postfach 5634, 4 DÜseldorf l, FRG

Professor I.J. Selikoff, Monnt Sinai School of Hedicine of the CityUniversity of New York, Fifth Aveue an lOOth Street, Ne York,NY 10029, USA

Dr J.C. Wagner, M=cal Reseach Conncil Pneumniosis Unit, LlandoughHospital, Pena, Glargan CF6 1X, UK

Dr J .K. Wagoner, Nationl Institute for Occutional Safety an Heath,Rort A. Taft Larataries, 4676 Columia Parkwy, Cincinti,Ohio 45226, USA

Dr J .A.H. Waterhous, Director, Reional Cacer Registr,Qu Elizabth ~dical Centre, Birmngham B15 2TH, UK(Vice-Chairman)

Dr P. V€steholm, Deputy ~ical Director, National Bord ofOccutional Safety and Health, Fack, S-lOO 26 Stoclm, Swen

3

CbserersDr W.J. Hnnter, Cossion of the Euope Conmnnities, Heath and Safety

Directrate, Bâtint Jean M:mnet, Avenue Alcide-de-GsPei, Kirchrg/Luxemurg, Great Duchy of Luxemurg

Dr R.J. Levie, Senior ~dical Scientist, Center for Occuptiona andEnvironmtal Safety and Health, Stan

fard Research Institute, ~lo

Park, California 94025, USA

Dr C. Levinon, Secreta Ceneral, Interntional Federation of Chemcaland Geeral Workers' Unions, 58 rue de M:illebu, PO Box 277,1211 Ceeva 19, Sw tzer land

Dr H. Ott, Commssion of the Euopean ecunties, EnviroruntalResearch Proam, 200 rue de la Loi, 1049 Brusels, Belgium

SecretariatDr L. Griciute, Chief, Unit of Envirorunta CacinogensDr J .E.H. Milne, Unit of Epidemology an BiostatisticsMrs D. Mietton, Unit of Chemcal Cacinogenesis (Library assistant)Dr R. rbntesano, Unit of Chemcal CacinogenesisMrs C. Parnsky, Unit of Chemca Carcingeesis (Technicai editor)Mrs 1. Petersch tt, Unit of Chemcal CarcinOÇenesis, i'VO, Ceeva

(Bibiiographicai researcher)

Dr V. Ponomrkov, Unt of Chemcal CacinOÇenesis

Dr R. Saracci, Unit of Epidaolog and BiostatisticsDr L. Tctis, Chief, Unit of Chemcal Carcinogenesis (Secretary

and Head of the Programe)

Mr E.A. Waler, Unit of Environnta Carcinogens

Mrs E. Ward, M:mtignc, France (Edi tor)Mr J .D. Wilbur, Unit of Chemcal Carcinogensis (Co-secretary)

4

Note ta th reader

Every effort is made to present the nonogaphs as accately aspossible without nnduly delaying their publication. Neverteless,

llstaes have occured and are still likel y to occu. In the interest

of ail users of these nonogaphs, readers are reqested to corricate

any errors observed ta the Unit of Chemcal Carcinogenesis of the

Interntional Agency for Research on Cacer, Lyon, France, in order that

the se ca be included in corrigenda whch will appe in subseqtvolurs.

Since the nonographs are not intended tobe a review of the

literature and contain only data considered relevant by the WOrkig

Group, i t is not possible for the reader to determne whether a certaistudy was considered or not. HCMever, research workers v.o are awae

of imrtat published data that may chage the evaluation are reqested

ta mae them available to the abve-netioned address, in order tht they

ca be considered for a possible re-evaluation by a future Working Group.

5

CONI

INDOCTlOO ...............;..................................... 9

.ABEsl ........................................................ Il

1. Chcal and Physica1 Data .......... ... . . . . . . . . . . . . . . . . . . . . Il1 . 1 Synnym and trade nas ............................. 12

1.2 Chemca and physical characteristics ................ 12

2. Production, Use, Occuence and Detection ................. 29

2 . i ProductCJ nnd lle ................................... 29

2 .2 OccureICE. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322.2 (a) Asbestos in the geeral environmt ................ 33

2.2 (b) Asbestos in the work envirorunt ................... 36

2.2 Cc:) Dostic exsure .................................. 38

2 . 3 Detector of asbestos ................................ 40

3. BiolOÇica Data Relevat to the Evaluation of CacinognicRisk to ~ ............................................. 42

3.1 Cacinogencity and related studies in anls ....... 42

3.2 Oter relevat biological data in anls ............ 58

3.3 Case report and epideological studies ............. 62

3.3 (a) Occutional exsure to cxrcially exloitedsotic:s .......................................... 62

3.3 (b) Srking and occutional exsure to asbstos ...... 69

3.3 (c) Non-ocuptional exsure to ccrcially exloitesources .......................................... 69

3.3 (d) Exure to asbestifor: mierals othr th miedasbestos ......................................... 70

3.4 Anyses of fibres in tissues ........................ 72

3.5 Asbestosis .... '...-.-.-'...'."'.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75

4 . Conts on Data Reporte and Evluation 80

APPENIX AScpe of th problem relate to asbetos exsure ............. 82

5. Referenc:s. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85

7

INDOCION

For a general introduction to the IA progam on th Evluationof th CacinOÇenic Risk of Chemcals ta Ma, th reader is referred tothe prearle gi ven in other recent volurs of the IA ITnogaphs, whchdescribs the workig procedures and criteria adopted by such Ybrking

Groups.

ln this volur several changes :Ln the usual layout of the rnno-

graphs have been made; namly, data which concem asbestosis and th

occurence of asbestos fibres in hur tissues, which would normlly

have ben considered in section 3.2, 'Oter relevant biolcxical data' ,have been considered in separate sections after the epidemological

studies. Section 4, 'Camnts on Data Report and Evluation', is

given in a unified fonn, without separating animl froID hum data.

ASBETO

Assto wa previously evaluate in Ocbe 1972 (IA, 1973).Since that tii new published data beca available whch were considered

by a WOrking Group especially conveed in 1975. The present WJrkig

Grup has made a final evaluation of all available data publishe or

accepted for pulication up to Decer 1976.

1. Chemcal and Physica Data

Asbestos is the generic nar used for a grup of naturally occurin

lleral silicate fibres of the serpntine and amhile series. Q)vern-

net agencies in vaious conntries, and industrial groups, curentl ycharacterize six fibrous silicates as 'asbestos' (Speil & Leinewer,1969; US Depat of Lar, 1975): the fibrous serptine lleralchsotile and the fibrous amhiles actino1ite, ansite, anthophyllite,crocidoli te and treili te .

Asbestos

Serntine1

Chsotile(whi te asbestos)

Amhiles

Actinolite AIsi te Anthophy lli te(bram asbestas)

Crocidoli te(blue asbestos)

Trerli te

Cuent usage of the tei: asbestos is restrictd to these specifiesilicates, although there are may minerals with fibrous crystal habits

tht occur naturally. These latter nuneral species, h~ver, either do

not possess such properties tradi tionally ascribe to asbestos as, for

intace, heat stability, thrml and electical insulation, the ability

ta be woven, staility in acids or aJ..alis, or do not occur in sufficient

concetrations for exloitation. The originl definition of th ward

asbesto is deri ve fran th Greek, 'incoustible'.

11

1.1 Synonym and trade :rS

Chem. Abstr. Reg. Serial No.: 1332-21 -4 Asbestos fibre

Asbesto12001-29-5 Chsotile

Serntine; 7-45 asbestos;

Avibst C; Cassiar AK;

Calidria RG 144;

ealidria RG 600

17068-78-9 Anthphyllite

Azbolen asbetosFeroanthophylli te

13768-00-8 Actinolite12172-73-5 Amsite

Mysori te

12001-28-4 Crocidolite14567-73-8 Trenlite

Silicic acid, calcium

magnesiur salt (8: 4)

1.2 Chemcal and physical chaacteristics

(a) Chsotile(i) Atomic strcture: On the basis of powder diffraction and

single crystal X-ray crystallographic studies and translssion electronrncroscopic and selecte area electron diffraction investigations,

chrsotile ha been shaw to be a culed sheet silicate, spiralled as ahelix aronnd a central capillar (Clifton et aL., 1966; Huggins & Shell,

1965; Jagodinski & Knnze, 1954a,b; Kalousec & Mutta, 1957; Ptdsack,

1956; Whttaer, 1963a; Yada, 1967; Zussm et ai., 1957).

Chrsotile is the fibrous mer of the serpntine lleral group,

possessing a rolled trioctaedral clay strcture; it is the magnesium

anloge of kaolinite (Der et ai., 1962). Half of chrysotile sheet

silicate is camsed of planar- linked silica tetraheda in a pseudo-

hexgonal arrangert. Here, all thee oxygens at the bae of the tetra-heda ar shaed in a con plane. All unhared apical oxygen in ths

12

sheet ':ix:Únt' in a single direction, abve th plane, towds an ad-joinig 'brucite' layer, whch is COIlsed of magnesium ions cordinated

octedrally with oxygen and hydrxyl groups. Two of the thee apical

oxygens in the tetrahedal shet replace hydroxy 1 groups to fonn the

bruci te layer. The cc:lete, single chrysotile structure consists of

al: 1 sheet structure of silica and bruci te, joined by shared tetrahedal

apices. The distance between adjacent cosite sheets is in the order

of 7.3 nm, with symtr elemt repeat every tw sheets, or 14.6 nr.Th dinsions of the brucite sheet (5.4 nm x 9.3 nm) and the silica tetra-hedral sheet (5.0 nm x 8.7 nm) indicate tht these basic unts are struc-

turally mismtdied. There are several nechansm by which the sheets

may 'chage' in size so that they will 'fit' over each other: (1) thebonds may stretch to fit, producing a llsshape nolecar arrangeit¡(2) smaller ions maY ente the ocedral brucite grup, or larger ions

may enter the tetrahedal silica group, thereby decreasing or increasing

the respetive sheet sizes ¡ or (3) the structure may be warp, wi th thelarger brucite sheet culing over the smler 'tridyte' sheet. Thelatter nechansm (3) appears to be the dannant nethod of structural

accormtion for chrsotile, al though the presence of trace netals and

maked disorder along speific crystallographic directions suggest tht

other factors acconnt for SaT of such accation.

The curature of chrsotile, its llsshape rond angles and resultant

chage distribution produce a strctue that may be considered to be

untable. A coison of the staili ty of the different serpntinellneral form (Nagy & Bates, 1952) clealy dernstrates this.

The chage on the surface of chrysotile in an aqueous medium is

controlled by the hydroxyl groups suronnding the magnesium ion. Beauseof th adsorption of hydrogen ions at the surface, a net positive charge

is produced (Speil & Leinewr, 1969). The surface is comnnl y hydro-

philic, sa tht Pacles of chrysotile fonn a stale suspeion in

water (Pudsack, 1956, 1961).

(ii) Chrsotile crystal polytyps: Cung of chsotile Ilstcormnly occurs around the a axs, Le., th hollow fibre tub axis

paallels crystallogaphic a, forrg a girdle of c axes. The structure

13

of chsotile is conplicate by the differet ways in which the COsiteshets are stacked. If adjacent sheets are stacked so tht magnesium

hydroxyl grups are offset in the sar direction and successive sheets

have the sar brucite oonfiguation, the resultig syrtr belongs to

the nonoclinc system, and the mieral species is tenæd 'clinocso-

tile'. Hawver, stacking of sheets may reverse sa that the net displace-

net is effectively cacelled. Ths results in an orthorharic syntry.

Ths lleral species is called 'ortho-chrsotile'. Another species of

fibre, ' para-chrsotile', is chaacterized on the basis of i ts tubular

developint parallel ta the b crystallogaphic axis. Ths vaiety occurs

only rarely.

Sa investigators indicate tht electron diffraction pattern ofchsotile fibres yield fibre patter of bath ortho- and clinochrsotiles;

i.e., natural chsotiles are corrm:mly nùtures of polyts. Ho~ver,single fibrils appe to be of ei thr one structural ty or the other,and single individua .fibrils with nùed chacteristics have not benobserved (Zussma et ai., 1957).

(iii) Fibrils and fibres: Elecron llcroraphs shCM that single

chsotile fibrils are hollow tubs (Clifton et ai., 1966; Lager &

Pooley, 1973; Laer et ai., 1974; Maer et ai., 1960; Yada, 1967).

Sa of thse microaph suggest that thre are chaels betweeindi vidua fibrils as well as interal capillaries. The internlcapillaries of chrsotile have ben studes and their diional chaac-teristics recrde: these range frcm 20-130 ru (Bacbllet, 1948; Lager

& Pooley, 1973; Lager et ai., 1974; Maer et ai., 1960; Ptdsack,

1961; Whittaer, 1963a; Yada, 1967, 1971). Oùter fibril dinnsionsof up to 600 nm (usually 200-300 nm) in width have ben reported(Whittaer, 1963a). Sone authors have suggested tht chsotile fibriL

diions are different in different geo10gical loclities, e.g.,Caadian fibrils tend to be larger than South African vaieties. Fibril

gro appers to be related to th process of crystallization and toboththe chemcal and physical environnt (Bates, 1959; Bate et aL.,

1950; Jagodinki & Knnze, 1954a,b¡ Kaousec & Muttat, 1957). A nore

recet paper (Yada, 1967) bas denstrate tht with a single lleral

14

specii th capillar and fibril wiòth may vary signficatly, and the

presen of chsotile fibrils wi thut th central capillar has bedennstrate. Chsotile fibrils may develop as bath 'cx:me-in-cne'

concetric cylindes and as proresive rolled shet helices spirallingaronnd a cetral capillar.

(iv) ChanstrMajor oxides: Th ideal crysta chemcal formla for chrso-

tile is X6 (Si40i 0) (OH,O ,F ,Cl) 8. X represents octaedally cordinated

cations of the brucite layer. Magnesium not conly occuies this

position up to th available 6.00 sites, although iron, nickel and

rnganese may be present at up to seveal teth of a percet (Table 1) .The Si poition represents th tetrahedally cordinate cation of the

silica layer and is alst entirely filled by silicon to the hypthetical

4.00 si te vacancy. Rael y, alumium may be present in the structure;the hydrxyl grup may in rare instaces be replaced by oxygen, fluorine

or chlorine. All substitutions are related ta original rock typ,

provenance and conditions of grCM.

The chemcal conpsition of chsotile is unfonn in corri-

son to tht of the amhilxÜe asbetos llerals. A corrison of th

e:i-rical (Xsition of ctsotile with that of naturally ocuring

fibres indicates that the latter tend ta be 'dirt': sar trace oxides

are always present. The high Fe2+ and Fe3+ contents usually result fro

contaation by magnetite, which 1S a ubiqutous accompying lleral

phase when the serptinized rock 1S an ultramfic ty. Calcium oxide

reflec serntine deposits originatig fro a silicified dolante.Mior and trace elemts in chsotile: Ni, Cr and Co have

be identified in trace annnts wi thn chrsotile deposi ts deri ve froultramfic (serpntie) lxes (Table 1). Iron is also ubiqutous.

Occasionally, other trace netals are observed, but their presence testo reflect that of trace lleral phases associate with the fibre. For

examle, high iron contet in Caadian fibres may reflect the presenceof bath ferrian nemlite and/or magnetite (Liebling & Lager, 1972).

The substitution of nickel and iron for magnesium in chsotile is

15

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conplace in deposits derived fror ultraric rock types (Lager et aL.,1972a,b; M:rgan & Holis, 1970; Morgan et ai., 1975). Such deposits

provide the bulk of chrsotile fibre ta the WJrld maket.

(v) Imurities

Cc:n mineral ÌIuri ties associa te wi th chsotile:There are a large numr of rok typs which ffa.y be presursors of, orassociated with, serpntine bodies. These include dunte, dolomite,

gabbro, hornlendite (amhiblite), norite, peridotite, picrites and

pyroxenite (Der et ai., 1962; Johanen, 1937). Alteration of theserocs to serpntine, accorrnied by the fonntion of lizardi te, anti-gori te and chsotile, rny also include the suri val of pre-estingmineral phases. Rok-fonnng mierals such as olivine and pyroxene may

surve the alteration procss and contanate the final I1neral fibre.Occasionally, nemlite, trelite, anthphyllite an a mmibr of other

fibrous llneral phases may be associate wi th the sertine boy. Oremierals, e.g., niccolite (nickel arsenide), cobaltite (cobalt arsenide

sulphide), arsenopyrite (iron sulphide arsenide), chrate (chollumoxide) or magnetite (iron oxide) may often be present in qutities

sufficient to faIm exploitale mieral deposits. Gelogical literatureis replete with report of the association of such ore deposits with a

serpntinized hast rock. Therefore, cheical and llneralogical data may

suggest not only eleintal substitutions within the chrsotile structure

but nore COnl y associate trace mieral phases as \Vll.

Chsotile fibre that has originate frorn sertinizeddolomites is often contaated with the cabonate mieral, calcite(Der et ai., 1962; Diller, 1919; Huggins & Shell, 1965). As with the

chrsotile fibre originating fra ultrarfic rock typs, the numr ofassociate contaant phases in carbonate rocks is high. Several papershave listed comn mierals and rntals associate with chrsotile (e.g.,Diller, 1919). Cc:n analytical techiques, generally X-ray diffraction,

have been used ta denstrate these vaious mineral associations

(Badollet & Gatt, 1965). As ia the case of trace netal anlysis, trace

llneral phases closely follow geological rock typ.

17

The qutities of trace mineral Ìlurities in chsotile

appear to range considerably (Speil & Leinewebr, 1969). Wh present,their paticle sizes tend to be exreil y smll, in the order of a few

hnndred llcrons and less (Badollet & Edgerton, 1961). Chrsotiles derived

frorn sentized dolomtes ted to have calcite integros of a size

simlar to tht of magnetite.

Occaionall y, the chrsotile fibril i tself may contain

qutities of anrphous material tht is of chrsotile aJmpition but

not necessaril y of the sar IIlecular proprtions. For exarle, i t has

ben noted tht the progessive leaching of chrsotile with distilledwater may yield what appes to be the llneral phase aipha-sepiolite

(Hagreaves & Taylor, 1946).

Hydrocarlxm traces: Adsorption of hydrcarl::ms onto the

chsotile surface has be docUInted (Haringtn, 1965; Harington & Ro,

1965). Natural organc contaation is far less con in chrysotile

than in croidolite and ansite, but contanation duing indus trialfabrica tion is apprentl y nore widespread th previousl y thought.

Storage of fibre in vaious containers is one such source of hydrocooncontaation (Carns & Gibbs, 1969).

Irurities added during prepaation: Occasionally,

imuri ties such as nickel -stel fragrnts are added ta the prouct duringthe procssing of chsotile asbestos. These are appently the resul tof abrasion of machiner by the mieral imurities. The ainnts of such

stel partcles are generally sml (Ayer & Lynch, 1967 ¡ Badollet, 1952).

Har lllling may increse considerably the nickel, chanum, aJbalt and

iron aJntet (Badollet & Edgerton, 1961).

(vi) Harsh and soft chrsotiles: It has ben reczed on thebasis of field observtion that the serptine mierài chrsotileoccurs naturally with a range of physical propeties. There apper tobe differences in the relative flexibility of chrsotile fibres derived

fran different geolOÇical localities¡ these have be terid 'harsh'

and 'soft' fibres (Speil & IeineW2r, 1969).

18

The relative flexbilityand 'feel' of the fibre bundle has ben

used to distingush between these typs (Da & Ford, 1957). Althughthe te 'hash' an 'soft' have be applied to certa fibre typsto suggest extre characteristics, fibres generally occu as gradations

betwee these mineral end-typs (Badollet, 1948). Occasionally, fibrebnndles are obsered that do not flex readily, tht possess characteris-

tics of harsh fibre typs, but that are not truly hash. These tend ta

be fibre bnndles of chrysotile intergrow intirtely with lleral

imurities. For exle, Canadian fibre tends to posess intergrowts

of magnetite ar nemlite paallel to the fibre axis. Although thse

fibres appe ta be harsh in the hand speclln, reival of th fibres

from the mineral matrix produces a soft flexible mieral species. A

sur of recogized properties of these fibre typ is gi ven in

Table 2.

The nature of the fibre bundle and the nechacal ease of reducingsuch fibres ta individua fibrils are directly related ta the relative

degree of harshness or softness. Soft fibres tend ta break ope easily,

producing a large surface area, which pets leaching of magnesium fran

the eXfsed fibre surfaces, increasing solution conductivity (Table 2).Th relative deee of fibril disorientation may be mesurd by varia-

tions in selected area electron diffraction pattern (Lager et ai. ,1974) .

(vii) Oter properties: The chemcal staility of chrysotile is

limte. When it is in contact with dilute acids or even with solutions

at pH of less than 10.8, magnesium tends ta be reived fro the fibre

surface (Hargreaves & Taylor, 1946). On a compative basis, the stail-

ity of chrsotile is generally much less than tht of th oth serptine

minerals (Nagy & Bates, 1952). Magnesium loss in vivo ha been dens-

trated by bath electron microprobe analysis of fibres in tissues and by

studies of neutron-activated fibres releaed in labratory anims(Lager et ai., 1972a,b: Morgan & Holms, 1970; Morgan et ai., 1975).

Chemcal degradation is accorraned by physical degradation as well(Jaurand et ai., 1976).

19

IVo

Property

FIBRE BULE

Fee 1

Tenacity (flexibility)

Size reduction (lengt)

Fibrilization of bundle

Surface area (equal aiunt ofmaterials identically size-redced)

INDIVIDUAL FIBRILS

Appearance under electron microscope

Indi vidual fibrils

Electron diffraction pattern

PHYSlCA PROPERIES (BU SALE)

PorosityFilter rates

Filtrate clarity

Conductivity (2.9% suspension)

M: leach (% NaCl eqivalent)

æECA PROPERlIES (BUL SALE)Structural water (dr ~ight)CaO content

1\203 content

Table 2

Chacteristics of soft and harsh chsotile

Soft fibre

Smth, silkyFlexble, may be bent ta? 90° without rupture

Poor, resists fibre axsbreakExcellent to goo, easilyopened

Average Canadian sanle:23 m2/g; sar as high as30 m2/g

Fibrous, thin filaintsmoerately translucent

Erty to partially-filledcapillarArce reflections, disorderedinter-fibril relationships

HighSlow

CleaAverage Arizona soft:22.2 ohm-1cm-1 (xl05)

0.27

12.5-14.5%

Trace to nil (Arizona soft)

Trace ta mior oxide(Arizona soft)

Hash fibre Reference

Hash, splintery Badollet, 1948

Stiff, rutures at ~ 90° Bado11et, 1948

Go, easily broken across Bacbllet, 1948fibre axsPor, tend to remn in Badollet, 1948tight bundles

Average hash : 11 m2/g;1

Badollet & Streib,sor as low as 4 m2/g 1955

Lath-like, electrn-densebundles

Filled capillaries

Single round or streakedreflections, ordered inter-fibril relationships

I.Fast

Cloudy

Average Arizona harsh:11.9 ohm-1cm-1 (xl05)

0.10

11.0-12.5%

Trace to mir oxide(Arizona harsh)

Trace to nil (Arizona hash)

Bacbllet, 1952;Bates, 1958;Zussm et al., 1957

Zussm et al., 1957

Bado11et, 1952;Zussm et al., 1957

Bado11et, 1948;Badollet, 1948Badollet & Streib, 1955

Bado11et, 1948

Pudsack & Reimchussel,1956

Pudsack & Reimchussel,1956

Badollet & Streib, 1955

Di 11er , 1919;

Pudsack & Reimchussel,1956

Di11er, 1919

The physica staility of chsotile is also linted. Chrsotile

appears to lose its crystalline character when i ts size is reduced

beyond a certain range. This ca be observed after chrsotile is ball-

lllled for period of rrre tha 60 seconds (Lager et ai., 1977). These

strctural chges ca be followed by neans of X-ray diffraction and

infra-red sPetrographic and other tehniques. Mechica energy firstbreaks th physicall y weak chemcal bands; chrsotile is ini tiall y dis-rupted along the stackig direction, as indicated by a loss of the (hOi)

reflections (Brindley & Zussma, 1957).

This is of paicular imrtanæ in tenu of interpreting biologicaldata in which anl expriItation is carried out using materials which

have been ball-iilled for size reduction. It has been shown that ball-

milling results in decreased haeilytic activity and in the activation

of free radicals on chsotile surfaces (Lager et aL., 1977).

A range in the densi ties of natural chrsotile fibres has been

observed: values for Arizona chrsotiles, derived fro serptized

dolomites, have been reported to be betw=n 2.19 and 2.25 g/ml (Huggins

& Shell, 1965); the density of chrsotile from Canada has be shown

ta be approxitely 2.56 g/rr (Kaousec & Muttat, 1957; Pudsack, 1956).

These reported ranges in denity of chrysotile have been attributed bath

ta mieral inurities and to the presence of magnesium silicate material

that 'stuffs' the central capillaries and fibril interstices in the

fibre bnndle.

Chsotile has also been shaw to possess paamgnetic properties,

whch ca be used ta prcruce alignt of fibres for connting and

sizing (Timrell, 1975).

(viii) The wide geological distribution of serptine rocks;

chrsotile as a contanant: Chrsotile asbestos is mied

as a non-metallic ore; hawever, the iineral itself is far more wide-

spread than previously thought. For examle, serpntine belts are asso-

ciate with nearly every major nonntain chain axis arnnd the WJrld

(Hess, 1955), and serptine is a cCin hast rock for sor ore deposits

(Bateæn, 1959). It has been shaw that natually occurring serptine

21

consists of riures of chrysotile an of antigorite (Nagy & Faust, 1956)

and th plat y phase lizardite. (Brindley & Zussm, 1957)". Therefore,exsure to chsotile may can fra a vaiety of rok tys in whch

chrysotile itself is not being mined as such. A nurr of fibrousmierals may be interdispesed wi th or assoiate with chrysotile, for

exale, amhible asbestos vaieties (Table 3) (Lager et ai., 1971;Pooley, 1976).

Table 3

Synonym for serptine-like rocks, alteration products an mieralstht may contain or be associate with chrsotile

Roks Mierals (Faust & Fahey, 1962)

serptine antigori te rnschaumverculi te antillite metaitetalc aqucreptite neolite

bal tinri te ophicalci tebastite picroli tel:eni te picrosmiedenti te porcellophi tedewey li te pyknotropehydrophi te retinali tejeninsi te schweizeri telizardi te terphylli temanrlite williamite

(b) Aihible asbestos mierals

The amhible asbestos mierals are each as exmplex as chrysotile.The follawing desçriptions are offered as an outline, and a tale is

provided for direct conprison of the different mieral speies (Table 4).

(i) Atcrc strcture: The amhible mierals are structurally

inosilicates, double-chains, cross-lined with bridging cations. Thestrcture is forr by co-planar sharing of two of thee oxygens at the

base of the silica tetraheda, which exends as a single chain along an

infinite axs. The double chin is completed by the third oxygen, which

is shaed between two tetraheda of opposi te, facing chains. These nni tsfo:r the asbestos fibre axs (De et ai., 1967; Erst, 1968; Whttaer,1960, 1963b).

22

Table 4

Amhile llerals directly or possibly relate to asbestos

Asbestos typ Asbestifonn-related lleral

actinoli te- ferroactinoli tetrerli te garnerite

hexgoni terichteitetirodi te

anthophyllite ferroathophylliteferrgeditegedri te

crocidoli te crossiteglaucophaemagnesioriebcki teriebcki te

ansi te cungoni t.egreritekupfferitenontai te

Th different anhile asbestos fibres possess this basic structure,with smll nofications brought abut by chemcal vaiation. Cation sub

sti tut ions wi thin the arhilx:Üe strcture rrfy interplan spacingsand the stacking angle of chain nni ts , referred ta as the be ta angle.Ths angle fonu the inclined plane of nonoclinic structues. Uni t celldinsions and beta angles are obtainable from any nur of reference

sources (Der et ai., 1967; Whittakr, 1960, 1963b). A review of such

properties, e. g ., space group syrtry, is gi ven in Table 5.

(ii) Chemstry: The calexity of th arhile asbestas llneralsca be illustrated by a brief an general description of amhile crstalchestr. There are several genral chemcal structural fo:rlae used

for all amhible llerals: (WX) 7-8 (Z4011) 2 (O,OH,F) 2 (Mason, 1958) or,

irre freqently, WO_i X2 Ys (Si40II) 2 (O,OH,F) 2 (Ernt, 1968). The cations

WX correspond to th structural site A, Hi, M2' M3 an ~. Soconfuion generally arises fror the description of Llie c.l-'!suy of

23

N.¡

Table 5

Mineral relationships and con substitutions of the amhibole asbestos typs

Asbestos fibre Related Geeral Crystal Cation in Comn cation substitutionmineraI syste chercal fonnula system & H4 site and resul ting mieraI

space group

anthophylli te anthophylli te- (FeM6) SiS022 (OH) 2 orthorhanic ttj!:Fe Mg ~ Fe ferroanthophylli tegedrite Pri (119 ,Fe) Si ~ AliAl gedrite

(ttj,Si) .. (Al,Al) gedrite..(!'B, Si) .. (Fe ,Al) ferrogedri te..

ansi te grunerite- (Fe6Hg) SiS02 2 (OH) 2 rrnoclinic Fe!:Mg Fe ~ Mg magnesio-grueri tecumngtoni te C2/H cumngtoni te

Fe ~ Mn magano-grueri temagano-cumngtoni te

actinolite- actinoli te- Ca2 (MgFe6)Sis022 (OH) 2 rrnoclinic Ca Fe ~ Mg complete gradation:treili te treili te C2/M ferroactino Ii te-

Ca2 (Mg6Fe) SiS02 2 (OH) 2 rrnoclinic Ca treili te

C2/M Fe ~ Mn tirodi te

crocidoli te riebcki te- Na (Fe~+Pe~+) SiS022 (OH) 2 rrnoclinic Na FeH ~ Al complete gradation:

glaucophane C2/H Fe2+ ~ Mg riebcki te-glaucophone

c:rstals in tems of structural acccrations of ca tioJ:J3 . The iiiter-changed notation for strctural and chemcal symls woulà be exressedas : (A)O_1 U~ Mi) (Mi Mi H2 M2 M3) (Si40ii)2 (O,OH,F)2. Therefore,

chemstr and strture are interdepedent and relate to factors suchas cation size and valence (Table 6).

Bas ica 1 y, the amhile minerals consist of chain structures, wi thnine strctural sites tht rny accmrate cations. Any change in ratios

of these different cations woulà change the mieral species. HCMver ,

for the different asbestos typs, there appears to be linted substitu-

tion in tenn of chencal species and of their locations in the structure(Table 5).

lithophyllite: Anthophyllite is considered to be an

ortorhomic magnesiumiron amhile with possible alumium subtitu-

tion. Ths mieral species fonn a patial solid solution with themineral gedrite, an alumiumrich fibre of sinlar proPeties (Table 5) .

Arsite: Arsite is an exloited variety of gruerite.

As part of the grueri te-cugtoni te solid solution series, arsi tetends to occur with nore iron than magnesium in its strcture. Maganese

substitution may occur in cx:mcentrations of up to 4% by oxide weight

(Table 5) .

Actinolite an trenlite: Actinolite and trenlite

apper ta fonn a solid solution series, representing end-rrrs of that

mieral group (Deer et ai., 1967). Both mieral species possess calcium

in the M4 structural site, with complete iron-magnesium gradations in the

Mi through M3 valence sites. Occasionally, maganese substitutes for

iron (Table 5).

Crocidolite: Crocidolite is the exloited fonn of the

rock-formg arhible mieral riebckite. Riebckite may chage

chemcally with replacernt of Fe2+ for magnesium and Fe3+ for alumium

(Table 5). For exle, magnesio-riebckite is mied as croidolite in

Bolivia (Speil & Leinewebr, 1969).

The chemcal contents of the amle asl:stos typs are given

in Table 7.

25

N""

Table 6

Chcal and strctural notations for the arhiboles

Cation site Strctural Cation Nuir of Chge of cation IDation in strcture Comrn eleints

notatio~ coordiation site cationsin unit cell

W Ah10 - 12 1 + ta ++ back of 2 ~ Na, X, Li

FC opposed diains x Ca"'X M4 6 - 8 2 + ta ++ edge of 4 =: c. Na, K

FCN adjacent Ca, Mn, Fe, Mg

chans x~-- "-y Mi, M2., M3 6 5 ++ ta +++ front of 2 "- Fe, Mg. Ti

FC facing Fe, Alfa

chains xx~Z Sir, Sin 4 4 +++ ta ++++ fonng Al

FC single chain ~ Sidunt

E. Ordering of size of sites: Mt ;: M3 ;: M2. ;: Mi

); A-sites freqently vacat; if M4 ;: 2, A-site is filled (Whittaer, 1960)

Ç. y-sitescan also be filled by Mn, Cr, Li, Zn

9. Al sOOsti tutes for Si at up ta i in 4

Table 7

Chemcal range of the asbestos typs~

Arsi te Anthonhvllite Croidolite Actinoli te Trerlite

SiOz 49-53 56-58 49-53 51 -56 55-60

Alz03 - 0.5-1.5 0-0 . 2 1. 5- 3 0-2.5

FeZ03 - - 17-20 0-3 0-0.5

FeO 34-44 3-12 13-20 5-15 0-4

M: 1-7 - 28-34 0-3 15-20 21 -26

Cao - - 0.3-2.7 10- 12 11-13

NazO trace - 4-8 .5 0.5-1.5 0-1.5

KzO 0-0.4 - 0-0 .4 0-0.5 0-0.6

HzO 2 . 5-4 . 5 1-6 2 .5-4 .5 1.5-2.5 0.5-2.5

Can trace eleints Ag, Ba, Ce, Co, Cr, Cu, Li, Mn, fu, Nb,

Ni, Sc, Sr, Th, V, Zr

Q. Based on suprior analyses of Muum qulity representative fibres

(iii) Minerals simlar to the arhile asbestos typs: Because

of the carlexity of the strcture of th amhiles and the wide range of

possible cation substitutions in term of size and valence, it is

i.rtt to note that a mmibr of minrals should be regarded as ak

to asbestos typs.. Table 4 includes a paial list of rock-forng

minerals mich may fonn fibres tht possess proprtes simlar to thse of

arhile asbestos typs occurring i:r- exploited areas.

(i v) Physical properties: The biological acti vit Y of the anhileasbestos tys is possibl y related ta physical properties as well as tochemcal properties. The wide variation in chercal strcture of the

amhible vaieties suggests that biologica activity is not restrictdto any one chemcal variety (Lager et ai., 1974; Pooley et ai., 1970;

TIrrell et ai., 1970). For exarrle, crocidolite te.rids to fonn thin'1er

27

fibres than amsitei in general, arosite tenòs ta fom thinner fibres

than anthophyllite. Diamter is the determing factor in the abilityof a fibre ta p2netrate the lung airways.

The surface charges of all of the amhible asbestos fibres are

negative ln aquus nedia (Prasad & Pooley, 1973). The magnitude of

the surface charge is different for each of the different fibre typs.

Staili ty in alkaline and acid environmts also varies considerabl y

and has ben studied in detal (Speil & Leinewber, 1969).

The earth' s crust, a o:mplex of multiple rock typs, is compsedpririly of silicate mierals (Wahlstrorn, 1956). Although the phy-

sical and chenca natures of thse rocks var greatl y (Polderaart,1955), perhaps only six mieral groups constitute the 'rock-formgassemlage' (Wahlstram, 1956), classified on th basis of their atomc

strctures and chemstry. It is of great Í1rtance to note thatchrysotile, the asbestos fibre used rrst widely thoughout Nort AIrica,1S not considered ta be an 1 abundat' llneral phase. Rather, alst

8% of the ear' s crust is compsed of amhiboles (Wahlstrrn, 1956).

Since rrst of the asbestos fibre typs are rnrs of that mieralclass, this fact is of particular importace. Asbestos termolog isnot conly used ta describ the rock-formg connterPi therefore,one might suspect that may llning areas of the VDrld represent sources

of potential asbestos exsure and èisease beause of their contet ofthese fibrous gangu minerals (se section 3 Ac) .

28

2 . Prouction, Use, Occuence and Detection

2.1 Production and use

Asbestos has ben used internttetly in smll anunts for thousas

of years. M:ern indus trial use dates frorn abut 1880, when the Qubechrsotile fields bean to be exploited (Hendr, 1965; HuePe, 1965).

Duing the next 50 years thre v.re gradua increases in prcxuction and

use: a cuulati ve total of sorwhat less than 5000 million kg had bemied by 1930 .

WOrld production has accelerated over the past four decades (Table 8);

for exale, world mie prcxuction increased by 50% bet~n 1964 and 1973.

ln the latter year, the two major prcxucing conntries were Cada (sales

v.re 1790 million kg) and the USSR (estited production, 1280 million kg) ;other conntries with significant mie production were the Republic of

South Africa, Rhodsia, the People's Republic of China, ltaly and the

USA (US Bureau of Mies, 1975).

Table 8

World production of asbestos

Yea WOrld production % Canada % USSR

(llllion kg)

19601 2 210 45 29

19702,3 3 490 44 30

19732 4 093 41 31

19742 4 115 40 33

19754 4 560 23 48

19764 5 178 29 44

1 Fran May, 1965

2 From Clifton, 1974

3 ~ Clifton, 1972

4 From Fagan, 1976

MJst asbestos is used in th constrction industry, in general,

acconnting for two thrds of the usage. Over 3000 uses of asbestos have

be idetified (Rosato, 1959); ÍIrtant uss inclu:e asbestos caæt

29

sheets and pipes, insulation materials, taping c:nnds and floor andceiling tiles (Hueper, 1965) (se also Table 9). The asbestos contet

of a prouct is Ilt necessarily an indication of its relative health

risk, for in may products th fibres are tightly round to the matrix or

are encapsulated. A potential health risk arises when asbestos fibres

are set free, e.g., during the drilling or sawing of asbestos cetsheets.

Friction materials constitute an imrtat class of asbestosmaterials. These include not only clutch facings and brakes for cars,

lorries, railway carriages and aeroplanes but also braking materials

widely usd in indutr for machinery. Asbestos-containing gaskets

are also often usd.

Insulation materials ofte cxmta asbestos. Asbestos materials

have be applied in blocs, or pipe-sections, or as asbestos cet, or

sprayed on in cc:nnds Which often contain rock wol, binders and other

agets. Sprayed asbestos materials are us for decorati ve and acousticpurses, as v.ll as for the fireproofing of strctural elennts inbuildings.

An exraordinar variety of other uses of asbestos ar know,ranging fro papier maché materials used. by school children and fireproof

clothg and gloves to fillers for plastics. . Such uss may be fonnd to

have considerable imct in te:r of public heal th ten, since large

numrs of people may be exsed. The sar perspetive may be vaid in

consideing end-prouct use of asbestos materials, espeially in th

constrction industi or in ship-building an ship repair. A single

insulation v.rker, cuttig asbestos bloc or nùing asbestos cent, maycause th exsure of may other workers roundaut, e.g., electrician,plurs, masons, bricklayers, ~r:ers and othrs. The imrtace of

such 'bystader' exure has ben emasized by the observtions ofHarries (1976) and Skidnre & Jones (1975).

Trerlite is not at present exploited as an asbestos mineral in

its ow right. Mateials tht incltre trerlite as a major com¡;X:)lent

are, hover, produce in may pa of the world. Thse include may

30

o:i-0'r-..C

fp(!fi.~~§

tUl0'(!r-~

~ ..tU

tJ~ ~

.. §

(! .,.U

l r-:: r-

'E §

(!~.Q§.,..L::~11U

l

;BUl

.sUl

.E,g

r-19~~ ~ ~ G

; ~ 00 o: ~ ~ ~ ~ r; ~ 1N

r-

B.,.r-r-È8'fi1t

CD

r-.o

B-,.~

0' 0'

. .o M

B-,.r-r8.,.()o\.U

MM

(!r-joU

l

g

CD

r-.

M\0.

I.o:.o

CD

\0r- M

. .o 0

00 N 0' \0 \0 ~ o: N o: i. 00 i- M

\0 00 M \0 N

i- M r- r- i. M

r- r-

.L

a (!.,. ~04 Ul

Ul

+J Ul

.L .L () .L

i: i:~ ()

~ ~ ~ ~04

Ul U

l t;B

B .~ ~

Ul U

l \. .,..8 .8 8 ~,g ~

~ ~

oo

i..\0.

r-r-

Û\

o.

00r-.o

o

\0 N

. ...

~ §-,.

tJ .L

i: tU

.,. 3t Ul

tU i:

i: H

Ul Ul Ul

tJ () (!-~ '¡ :-.L Ul .L

~ ~ x

u i: ~

\. \.i ~

M\0i-r-19~

o:i-0"r-..

§~.,.r-U8f:tU

l

31

indus trial p:ders referred to as talcs or tremlitic tacs (Pooley

& Rolands, 1977; Rohl et ai., 1975).

Anthophyllite is a talc-like fonn of asbestos; it is use as anindus trial talc and in par-processing, plastic products, asbestos

CeInt pipes and friction materials (Clifton, 1974). Oter uses aredescrib by Rosato (1959).

Known comrrcially exloi ted deposits

Chsotile: The largest corrcial deposits of this mineral are inth USSR and Canada. It is also mined in the People' s Republic of China,

Cyru, L tal y, southern Africa and the USA. Recentl y, an ope-pit llnehas begu production in Australia. ln the past, sml aInnts were lled

in Corsica (Boutin et ai., 1976).

Crocidolite: rbst of this fibre cones from the nort-western Cape

and Transvaal areas of South Africa. ln the past, smll aInnts were

Ined in V€stern Australia (WittenOC Gorge) and Bolivia (Chichaba).

Arsite: Tranvaal, South Africa, is the ma source of this typof fibre. An identica fibre has be found in India and will be pro-

duced under the nar of mysorite.

Anthophyllite: This fonn of asbestos was exloited in Finand

nntil 1974; smller qutities are fonnd in a num of other conntries.It is a conmn contamnat of talc deposits in the US (Kleinfeld et ai. ,1974; Pooley & Rowlands, 1977; Rohl et ai., 1975).

Trenlite: So limted llning of trelite fibres was carried

out in the US and in the Far East. The fibre nCM exists primrily as

a natural contamnant in othr exploited materials, e.g., tac (Kleinfeld

et ai., 1974; Pooley & Rolands, 1977; Rohl et ai., 1975).

2 . 2 Occuence

The occurence of asbestos in the general or occuptional environ-

net has ben reported in various unts of neasurent; in workplaces,

air units include llllion paticles per cuic foot (mppcf) or, irre

recetly, ninr of fibres :; 5 ll per ml and million fibres pe m3;

32

in amient air sanles, values are generally reoorded on a gravi.rætric

basis, e.g., ng/m3.

It would be desirable to have a. conversion factor in order to

relate amient asbestos levels to ocupational levels; however,

attets to formlate such a conversion factor have generally been

unuccessful because of large variability(NIOSH, 1977). This is to

be excted, as amient levels are ~renerall y detenned by tranmissionelectron llcroscopy, whereas phase contrast optical microscopy is used

to neasure occupational exsures. ln addition, teciques used ta

prepae sanles for electron microscopic observation may cause altera-

tions in fibre size (dianter and lengt) distributions. Hawever,

th direct tranfer techiqu may overcx these difficulties (Sebastien

et aL., 1976a).

~surerts of asbestos in fluids, including water, beverages,

etc., have ben exressed as fibres per nù, fibres per 1 or ng per g ofsamle. For nore details concerning the problem in detecting asbestos,

see section 2. 3 .

(a) Asbestos ID the general envirorut

Air: Concentrations not exceedig 100 ng/m3, and usualy less than

10 ng/m3, asbestos fibres are present in the geneal urba atmsphere(Holt & Yonng, 1973; Nicholson & Pnndsack, 1973; Sebastien & Bignn,1974; Sebtien et ai., 1976a; Selikoff et ai., 1972a). However,

concentrations of 10-5000 ng/m3 asbestos fibres have ben reported neasaæ factories using asbestas (Nicholson et ai., 1975; Rickards, 1973).

Contaation of the air inside buildings can ocur fi: dage or

erosion of asbestos-sprayed materials or from working wi th asbestos-

containng materials. Nidiolson et aL. (1975) fonnd, in 19 buildings

investigate, values ranging fran 2-200 ng/m3. Sestien et aL. (1976a)

found levels as high as 800 ng/m3.

ln an elerta school in the US with a spray-forr, dat asstos

rof, asbestos fell intennttetiy ta leave dust on th suace of thefurture. Th intae filtes of th ventilation syste which recircuate

the schol-ro air ære clogged with asbstos fibres, an personal salers

33

on schol chldren sh tht up to 3.8 asbstos fibres greater th5 l. in 1eng pe ml of ai oced with th scl (US Depat ofHealth, Eduction an Welfare, 1972a; Young, 1972).

Levels of asbestos fibre contaation in buildigs appear to berelate to the application process used on interior surfaces (Nicholson

et aL., 1976). 'Dry' proesses, in which no liqud is added to matrix

binders, ted to deposit the insulation material as a loose 'fluff'.

This material disintegrates on touch and cat withta the abrasion

of air rnvet.The lengts an diarters of asbestos fibres fonnd inside such

buildigs are simlar to those describe by Gibs & Hwg (1975) for

fibres samled in various work environnts (Sestien et aL., 1976a).

ln bath situations, the percetage of fibres with diarters less thn

o .5 ll and wi th lengt greater than 5 ll was abut 20% for amhilleand 1% for chrysoti le.

Table 10 indicates various expsure levels in the air to which

the gen erl poulation may be exsed.

Table 10

Examles of exsure levels in aira

Exsure Asbestos concentration (ng/m3 )

USA Paris

Amient air (urba) 0.1-100 0.1 - 10

Buldigs sprayed 0.1-800 0.1-800with asbestos

Nea asbestos 10- 1000 -spraying

Near asbestos 10-5000 10- 3000factory

aFrom Nicholson et ai. (1975) and Sestian et ai. (1976a)

The presence of asbestiform mierals in non-ccxrcial depits is

widespread in may geologica formtions¡ the fact tht fibres ca be

34

released when th rocks are crued provides a furer soce of oonta-

mition (for discusion of other fibrous llerals, se section 3.3 d) .In ths regard, the us of asbestos nue tailings on roads may prove to

be an imrtt hazard to the general public, an the use of asbestos-

containing, quried, cruhed roc may also be a potetial risk. This

question was raise in a recet coi ty sury of lung cancer (Newn

et aL., 1976). Simlarly, the use of asbestos stucc, erloyed ascladding for buildigs, may result in environrtal exsure. Theincipient danger fror discaded asbestos is indicate by the finding of

60- 100 million asbestos fibres/m3 in the amient air in the vicinity of

waste dus (Ha & Blaszak, 1974).

Water: Average concentrations of asbestos in dring-water

ranged from 0.3-1.5 l1g/l as nesurec in easter US river water(Nicholson & Pudsack, 1973). Levels of 2-173 rrllion fibres/l wee

fonnd in Canadian tap-water, the highest levels beng fonnd in nnfiltered

tap-water near a minig area (Ctmgh & Pontefract, 1971).

Levels of up to 12.46 l1g/l chrsotile asbestos, as detered byelectn microscopy, were found in the Jumta ar Connecticut ri vers

(Arica Water WOrks Association, 1974). A study of the Great Laes

and St Lawrence River byters ShCMed average concentrations of abut

1. 7 million asbestos fibres/l. Locations with higher counts wee found

along the north shore of Lae Suprior betwen Silver Bay and Duluth, along

th St Clai River, dostrea fra .rntreal, ar in th asbestos midistrict in th provin of Qi (Cok et ai., 1974; Zielhuis, '1977) .

Foo: The asbestos contets of food have not be well investigated;asbestos filters and tac, whch may contain asbetos as an inurity,

may be used in the maufacture of procssed foo, e. g ., sugar, veetale

oil, lard and coted rice (~liss, 1971; Wolff & Oe, 1974).

Beverages: Asbestos fibrils, considered to be chsotile, at levels

of 13-24 llllion fibres/l have be fonnd in samles of one ty ofspirit probaly filtered with asbestos filters (Weh & Plantholt,

1974) .

35

Biles & Eìrson (1968) and Cunningham & Pontefract (1971) a.lsoreportd the occurence of asbestos fibres in British, Candian and

Arrica be (1-6.6 million fibres/l). Asbestos fibres were fonnd in

various sherries, ports, venruths and soft drins (1.7-12.2 millionfibres/l) (Cuingham & Pontefract, 1971).

Pharceuticals: Chsotile asbestos has been fonnd in sar sarles

of parenteral drgs (range, 1-1000 ng/g) (Nicholson et ai., 1972). ln

the US, no asbestos-contaning or other fibre-releasing filter may be

used in the rnufacture, processing or packaging of such products, nnless

it is not possible to maufacture that drg prodct or conent withoutthe use of such a filter (US Fcx and Drg Admistration, 1976).

Detal practice and dental school labratories: Asbestos-oontainig

Peiodontal packs are saætins used after gingival surger (Infante &Len, 1976). ln dental schools, asbestos tape is used to hold goldtht is heated and then cat into rnulds during dental labratory pro-

cedures. This may be a potential problem and has not ben evauated byadeqte industrial hygiene monitoring.

(b) Asbestos in the work envirorunt

Asbestos contaation of th air ca be caused by spraying of

asbestos material ei ther for fire protection or for decorati ve or

acoustical purses; contaation wa fonnd to be high during theapplication of sprayed mieral fibre (Nicholson & Ptdsack, 1973).

A caison of asbestos concetrations in air nnder different circu--tances as neasured by electon rncroscopy is as follow: nea asbestos

spraying, 10-1000 ng/m3; during a lllling operation, 10-5000 ng/m3;

in other occuational exsures, 1000-:/ 100,000 ng/m3 (Nicholson et aL.,

1975) .

Fibre concentrations in various asbetos-using industries in the

US prior to 1971, as determed by optical and electron microscoy, aregi ven in Table 11.

36

Table 11

Concentrations of fibres in various asbestos-using industriesin US before 1971s!

Industry Rage of nes Rage of(fibres ? 5 llm/ml) indi vidua samles

(fibres ? 5 llm/ml)

lextile 0.1-29.9 0.0-143.9Insulation 0.1-74.4 0.0-208.4Paper packig and asphalt 0.2-13.6 o . 0-18 .9

prodctionCert shingles, mill- o . 1 -4 . 4 0.0-16.6bord and gasket

Friction 0.1-14.4 o . 1-32 . 4

Cent pipe 0.2-6.3 o . 0- 13 .4

a From US Depat of Heath, Education & Welfare (1972b)

Airborne asbestos samling programs do Ilt at present, however,

attet ta discrimate betwee the various fibrous mierals present

in dust samles. Table 12 gi ves a ccarison of the lengt distributions

of airborne asbestos fibres, as detered by electron llscroscopy, in

various industries in the us.

Table 13 gives th contents of asbestos fibres, by products and

fibre typ, in asbestos proucts prouced in vaious EE conntries.

Ocationa exsure in situations other th the traditionalasbestos processes (llning, lllling, factor producton and haing ofasbestos products) has be shaw to be of increasing imrte. Suchexsures occu duing end-prouct use, as aTng asbestos insulationworkers (Selikoff et ai., 1964), ammg brak repair and brake mainte-

nance workers (LoriIr et aL., 1976; Rohl et ai., 1976, 1977), and as

the result of indirect occuptional exsures, p,icularlyin ship building and ship repar (Harries, 1968, 1976), an in th

constrction industr. Oter exsures occur in relation to inspection,repar and matence work on asbestos-cntaining strcturs ar

37

Table 12

Lengts of asbestos fibres in air nea vaious US inUstries a

Opration Fibre rædian % :: 5 lltyp lengt ( llm)

Texile clu:ysotileFibre prePaation & cadig 1.4 4

Spining, twisting, weaving 1.0 2

Friction chrysotileMiing 0.9 2

Finishig 0.8 2

Asbestos-cert pipe chrysotileMixig 0.9 2

Finishig 0.7 1

Pipe inulation amsi te

Pipe formg 4.9 51

a- Fran Dent et ai. (1976)

eq:rt, in refineries and chemcal plants, buildigs, railway loc-

notives and wagons, shipyards and J?I1 plants. Increasingly imrtant

exsures ca be excted to result fror buildig delition and waste

disposal (US Environntal Protection Agency, 1975). Thse could pose

a considerable problem, in view of th very large amunt of asbestos

nCM in place as the result of th cuaulative us of th material during

the past centur. Exures may also occu during the v.ing of

asbestos safety garnts (Gibbs, 1975), during cleang operations on

buildigs fOi:rly sprayed with asbestos (Skidrre & Jones, 1975) and

during th hailing of bags fonærl y used in the transprt and storage

of raw or lllled asbestos (US DePant of Lar, 1975).

(c) Dotic exureDostic exsure of househld contacts to asbestos may ocur fran

dusts brought hor on workers' clothes, shoes, hair, eqpænt, etc.

(Andeson et aL., 1976; Newhuse & Thæpson, 1965; Wagner et aL.,1960). Nicholson et ai. (1975) found asbstos levels ranging fran

100-500 ng/m3 in the houss of workrn.

38

Table 13

Asbestos proct and thir asbestos contets in Eæ countries a

í?roduct

Asbestos-ceit buildig products

\sbestos-cert pressure, sewage anddrainge pipes

Fire-resistat insulation boards

Insulation prodcts, including sprays

Jointings and packings

Friction mateialsTexile proucts not included abve

Floor tiles and sheets

rbulded plastics and battery boxes

Fil1ers and reinforcets and pro-ducts made thereo f (fel ts, rnll-bord, paper, filter pads for winesand bers, nndeseals, matics,adhesi ves, coatings, etc.)

a . Th .- From Zie uis (1977)

Approx. asbestoscontent (% wt.)

10- 15

Asbetos fibrEt~C,A,Cr

12- 15

25-40

12- 100

25-85

30-70

65-100

5- 7 . 5

55-70

C,Cr ,A

A,C

A,C,Cr

C,CrC

C,Cr

C

C,Cr

25-98 C,Cr

b A = aiite¡ C = chrsotile¡ Cr - crocidolite (not used in allEE conntries)

Oter darstic exsures, also vlÌdespread, are para-ocutional

exsures from housold repairs and do-it-yourself constrtion usingasstos-containing mateials, such as asbestos cet sheets, plaster

fillers and wal-joing connds Wahl et ai., 1975), furce andheating eqplnt cets and other repair materials. Such exsures

rny increse as more an nore householders nndertake their CM

rnintainace ..rePars .

39

2.3 Detection of asbestos

Procedures for the sarling and neasur6ænt of airbrne asbestos

dust by the rærane filter ræthod have be describ (Asbestosis

Reseach Conncil, 1971a,b). These procedures have be evaluated in

detail by the National Insti tute for Ocupational Safety and Heal th

(NIOSH, 1977) 0 A report on inter-labratory a:ison of the connting

of sarles obtained by this method is gi ven by Bekett & Attfield

(1974) .

Phase contrast-optical rncroscopy is used in the routine exna-tion of dust sarles beuse of i ts low cost and speed of Peformce.However, it ca provide only an index of fibre presence and of th size

and optical properties of paricles that may be used to identify indi-

vidual fibres. The techiqæ is limted, since only the largest fibresin a sanle can be see, and, when erloyed for identification purses,i t is CUrsor and reres an exprt llcroscopist to interpret theresul ts .

X-ray diffraction techiqus have be used to establish thepresence of asbestos, but they canot differentiate betwn the fibrousand non-fibrous fonn of these llerals. Quntitative asbestos deter-

miation, using X-ray techniques, is colicate by the rnthod used for

sanle preparation an by the presence of minerals which may display

X-ray reflections in simlar positions to those of the asbestos minerals

(Kean & Lynch, 1970; Rohl & Lager, 1974; Rohl et ai., 1976). It

also reqres th prepaation of stadads for calibration purses.Miim detection levels of 2.0 % weight for anthophyllite, 0.25 % forchsotile and 0.1 % for tremli te have be reporte in talc (Rohl &

Lager, 1974). The techques requie bulk sanles which are notavailablein rrst environmtal sitUc-itions.

Differential thrml anlysis has been used to determe chrso-tile asbestos fibres in bul talc samles but has not beused forenvironntal samles. Differential therml analysis, like X-raydiffraction, is not caPale of differentiating betwee asbestos fibres

and their non-fibrous mieralogical pol yrrphs. A mi detection

40

level of 1% chsotile by weight has be reported in talc (Schelz, 1974).This level of contanation ha, hover, rarel y be observed in natural

talcs.

Both transmssion and scaing electron llcroscopy have been used toidentify and quantify asbestos fibres. The scannng elecron microscope

ca give only norphological informtion, uness it is fitted with energy

or wave-lengt disPesive X-ray spectroneters with which llcrohemcalanalysis of single paticles can be perfonn; this techque was usedby Beckett (1973). Transsion elecron llcroscopy is a rnuch noreversatile techique, since wi th this nethod paicle rnrpholog ca beaccuately observed and electron diffraction patterns are displayed(NIOSH, 1977). Microemcal analysis of particles (electrn llcroprobe

anlysis) ca be obtained when the technque is used in conjunction with

X-ray anytical eqpæt (Jauran et ai., 1975. Lager & Pooley, 1973;

Lager et ai., 1972a,b; Pooley, 1975). The latter techiqu allow thecollection of norphological, strctural and chemcal data tht allownnique identification of all single submicroscopic fibres that ocur in

the environnt.

41

3. Biological Data Relevant ta tl1e Evaluation

of Carcinogenic Risk to Ma

3.1 Carcinogenici ty and related studies in anims

(a) Oral admnistration

Rat: Groups of 32 \vistar SPF rats ~re fed 100 IT/day ltalian talc or/

UICC Cadian chrsotile in mated m:Llk power on 5 days/wee for 100 days

over a 6-nonth period¡ 16 controls 'Yvere fed only mated milk. Thenean lengt of surival fro the stat of feeding were 614 days for

those given tac, 619 days for thse given chrsotile and 641 days in

contrls. 'l gastric leicmosarcoma were observed, 1 in an anl fed

tac and the other in 1 fed chsotile. None of thse tururs ocred inthe oontrols (Wagner et ai., 1977a).

Thee grups of 25 male and 25 femle 10-wee old Wistar rats wereeither nntreated, give 50 IT/kg bw/day asbestos filte material contain-

ing 52.6% chrsotile asbestos which was powdered an added as a water

suspeion ta the diet, or given 50 mg/kg bw/day talc in the diet for

life. ln the group give asbestos filter material, the average surval

ti1 was 441 days. Amng 42 anls available for study, 12 malignanttururs with netataes were fonnd (4 kidney cacinomas, 1 lnng carcinoma,

3 reticulurcell sarca and 4 liver-cell cacinomas). One lnng adenma,

2 cholangian, 2 paillans of th forestanch and 2 rrry fibroadenoms

were also observed. ln th group receiving talc in the diet, the average

suriva li was 649 dayS¡ arg 45 rats exanned, 3 liver-cll carcino-

mas and 4 m: fibroden ~re seen. ln nntreated controls averagesurval ti1 was 702 days¡ 2 liver-cell carcinoma an 5 rn fibro-

adears occued arocmg 49 anims. The increased incidence of malignttururs in rats given asbestos filter material in the diet was significat

cced with tht in controls (P -: 0.01) (Gibl et ai., 1976) (The WOrking

Group noted tht th exact oorrsition of the asbestos filter material was

not givenJ.

42

(b) Inhlation

rbuse: Nordm & Sarge (1941) exed 100 white mice to a highconcetration of chrsotile dust for 72 hours. After 6 ~eks, asbestos

boes and fibrosis W?e observed in the lungs of all mice, and after13 weks abut 50% had hyprplasia of the epi thelial cells of the luns.

'I carcinomas were see in 10 llce suriving 240 days.

Lynch et ai. (1957) exsed 8-w old AC/Fi hybrid mice by

inalation to a cxrcial prepaation of chsotile asbestos for

8-12 hours/day on 5 days/wee for 17 rrnth. ln animls killed at the

end of expure, a higher incidence of rn tiple pulnnar adeIDmas was

obsered in the exsed group (46%, 58/127), th in the controls (36%,

80/222) (This result is Ilt statistically significat (P? 0.05)).

Rat: Gross et ai. (1967) observd tururs of the lung in rats

exsed repetedly to a me concetration of 86 m:3/rn3 chsotile dustfor 30 hours/we. Twenty-five of 72 rats suriving for 16 rrnths(li of apPerance of first turur) or longer develope 28 lnng tururs

(17 adenocarcinoms, 4 squs-cell carcinma an 7 fibroaarco),

whereas no such tururs occured in 39 controls. The authors suggested

tht the presence of trace netas frem the hars of th LLLL used to

prepae the fibre was a factor in the induction of these tururs.Howver, this suggestion was not confirr by subsent exprints

(Wagnr et ai., 1974).

Reves et aL. (1971) fonnd squanDus-cell carcinomas of the lungs

in 2 of 31 rats which suri ve exsure to croidolite for 2 yeas at acocetration of 49 mg/rn3 for 16 hours/week. Five rats in a grup of

40 exed to chrsotile develoPe pulnnar adentosis, but nomalignant tururs were observed aTng rats exse to either chrsotile

or aTsi te.

ln a subeqent exrimt, Reeves et ai. (1974) exsed groups of

69 Charles River CD r~ts to ball-rlled crocidolite, aTsite and chr-

sotile for 4 hours/day on 4 days/wek for 2 years, at nean concentra-

tions of abut 50 mg/rn3. Th results are given in Table 14.

43

Table 14

Inhalation cacinogenesis fro various fonn of asbestos in ratsa

Fonn of asbestos Numr of tUTurS

None None

Arsi te 2 pleural nesothelicrsCrocidolite 3 squus-cell cacinoma,

1 papillar carcinom and1 aderarcincr, all of lnngs

Chsotile 1 papillar cacinan an1 squus-cell carcinom of

lnngs and1 pleural nesothelian

a- From Reves et ai. (1974)

(It is imrtt to note tht thse rraterials were corute by

vigorous nechanical lllling (ball-mi.lling for up to 240 hours) , which

nndoubtedly altered the fibre propeies (Lager et aL., 1977; Occella& Maddaon, 1963)).

Reves (1976) produce pulm:maly tUTurS in rats with all thee

major tys of asbestos following exsures of 4 hours/day on 4 days/

we for 6-24 nonth to dust prepaed by hamr-lllling, at ne

concetrations of approxirtely 50 rr/m3. Exsur ta chsotile

yielded 2 lnng cacincrs an a nediastinal fibrosarco (a 5% incidence

of maignancy aTng suri ving animls); exsure ta aTsi te prouced the

sar 5% incidece of malignancy (1 lung cacinma, 1 fibrosarcoma and 1

mesotheliom); and exsure to crocidolite yielded lung cacinom in 14%.

It is interesting to note tht optically visible fibre connts wee 54

million/m3, 864 million/m3 and 1105 million/m3 for the 3 different typs of

asbestos, respectively, indicating that while th abnspheric concentra-tions were the sar in tenu of weight/volur, the optica fibre connts

wee dissimlar.

Wagnr et ai. (1974) exsed groups of CD i\Tista rats to the five Uiæasbestos sales (arsite, anthphyllite, crocidolite and Rhodesian and

Cadian chrsotiles) at concetrations of abut 12 mg/m 3 respirable dust

for 7 hours/ day on 5 days/week, for several length of expsure:

44

one day (7 murs), 3 nonths, 6 rrnths, 12 JTnths or 24 mnths.Ät theend of the exsures, the annnt of dust in the lungs of anls exsedto the tw chrsotile sanles was much less th tht in ans exsed

to the thee amhible samles. However, all typs of fibre producedasbestosis, which was proressive after rerval from the dust. Futher.-

nore, whereas no carcinans of th lung wee foun in th control group,

cacinans of the lnng and ræsothelior were denstrated in the groups

exsed to Canadian chsotile and ta the amhibles. On Y cacinorsof the lung were see with Rhodesian chrysotile (see Table 15). An

increasing incidence of neoplasrn was observed wi th increasing exsuresto each fall of asbestos. Even as little as one day of exsure- providing the animls were allow to surive and were obserd -produced neoplasia (see Table 16).

Wagner et ai. (1977a) coed rats exsed for 2 years to a pure,

non-fibrous cosrtic talc with another group of rats exsed to superfinechsotile. Simlar degees of fibrosis were fonnd in each group, while

one adenocarcinom was foun in an animl exsed to the chsotile.

oter species: Groups of 20 rabbits, 32 guea-pigs and 68 gerbils

were exsed to abut 48 mg/m3 balled-rlled crocidolite, arsite andchrsotile for 4 hours/day on 4 days/~k for 18 rrnths. No turrs weresee; hcwver, surval tins after 18 nonth were Ilt reported

(Reves et ai., 1974).

(c) Intrapleural adnistrationRat: All c:rcial typs of asbestos have prouce nesothelioma

in CD Wistar rats (Wagnr et aL., 1973). A dose of 20 mg of the 5 urcc

stadard reference sanles - crocidolite, ais ite , anthophyllite, eadianand Rhodesian chrsotiles .. produced various numrs of nesotheliors(Table 17) (Wagner et ai., 1977b).

Stanton & Wrench (1972), using a dose of 40 mg asbestos dust on

gelatin-coate fibre-glass pledgets, fonnd that 3 of the UICC sales,croc idol i te, arsi te an Rhodesian chrysotile, all produced nesothelio-

mas in abut 60% of Osborne-Medel rats. Pylev & Shad (1973) induce

37.5% nesothelian with 3 doses of 20 mg of a Russian chrsotile.

45

Table 15

Ni.rs of rats with lung tururs or rrsotheliors after expsure ta various fonn

of asbestas thougl1 inlationii

Fonn of asbestas No. of Adenocinomas Saus-cell r1esothe1 ioianimls cacinom

Ansi te 146 5 6 1

Anthph.y lli te 145 8 8 2

Crocidoli te 141 7 9 4

Chsotile(Candian) 137 II 6 4

Chsotile(Rhodsian) 144 19 II 0

None 126 0 0 0

iiFrom Wagner et aL. (1974)

Table 16

Numrs of rats with lung tUlrs or rrsothlians after various lengt.1-s of expure

ta various fonn of asbestas throug iIÙalatioJ!

Lengt.1- of No. of No. with lung No. wi th pleural % of animls

exsure animls cacinomas irsothelians wi th turuis

None 126 0 0 0.01 day 219 3!2 2~ 2.33 irnths 130 8 1 5.06 irnths 90 7 0 7.8

12 irn ths 129 35 6 31.8

24 irnth 95 37 2 41.0

~ From vvagner et al. (1974)

!2 2 exsed ta c..'1rysotile and 1 ta crocidoli te

~ 1 expsed ta arsi te and ore ta crocidoli te

46

Table 17

Percentage of rats developing ræsothelian after intrapleural

admstration of vaious mate rials a

Material % of ratswith nesothelioms

SFA chrsotile (suprfineCandian samle)

urcc crocidolite

UICC amsi te

urcc anthophylliteUICC chsotile (Candian)

urcc chrsotile (Rhodesian)

Fine glass fibre (coe 100),median diameter, 0.12 llm

Ceramc fi93e, diamter,0.5-1 ll-

Glass pcerCoase glass fibre (coe 110),

nedian diamter, 1.8 llm

66

61

36

34

30

19

12

10

3

o

a Fro i-vagner et aL. (1977b)

b- Wagner et ai. (1973)

Donna (1970) also observed neothelioms in Sprague-Dawley rats treated

witli a single dose of 67 m: of chsotile, amsite or crocidolite.

Simlar results ~re obtained by Reves et ai. (1971) with chrsotile and

crocidolite. Evdence that the response to chrysotile an crocidolite

was dose-related was provided by Stanton & i-vrench (1972) and Wagner et

ai. (1973) (see Table 18).

Th suggestion has ben made tht natural oils and. waes (Haington,

1962; Harington & Roe, 1965) and contat ails from milling of the

fibre (Ro et ai., 1966) or from jute or plastic storage bags (Co &Gibbs, 1969; Harington, 1965) contribute tothe incidence of pleural

tl.S . Ho~ver, samles fra which the oils had be rerved gave very

47

,¡00

Table 18

Dose-response data following intrapleural admnistration of asbestos ta rats

Haterial Dóse No. of rats with Total no. % of rats Reference(mg) irsothelioms of rats wi th tururs

SPA chrsotile 0.5 1 12 81 3 11 272 5 12 424 4 12 338 8 12 62

~vagner et a i.(1973)

Crocidoli te 0.5 1 11 91 0 12 02 3 12 254 2 13 158 5 11 45

UICC-SRA 1 2 25 8crocidolite 2 5 23 22

10 Il 27 4120 12 25 48 Stan ton &

40 14 23 61 Wrench (1972)

Hand-cobbe 1 4 30 13virgin 20 10 24 42crocidoli te 40 18 27 67

simlar result.s ta those obtained wit:h u.ntreated fibre (Wagner & BerD..,

1969; Wagner et al., 1973).

The fibre diamter, lengt and shape may be imrtt. All of the

8 sePaa te sub-samles which were poled in the UICC Canadian chrsotih~

reference sanle (Timrell & Rendall.. 1971/72), when ground separately ta

a finer fXder, produced a higher incidence of nesothelicms th didthe poled sanle. The highest incidence (69%) was produced by 20 mg

of a sepaate, suprfine chrysotile samle fractionated fran corrcial

grade 7 asbestos by water sedintation (Wagner et ai., 1973). Using

UICC crocidolite, Staton & Wrench (1972) found tht partially pulverized

material induced fewer rrsothelicms than did the stadard, nnpulverized

fibre. Prolonged grindig ta fine sizes is known ta destroy crystalline

structure (Lager et ai., 1977; Occella & Maddalon, 1963). Stanton

(1973) shaved tht fibres of other m:-iterials, including glass, could

induce rrsothlicms, but only when t:he diamter was of the sar order as

that of asbestos, when mesured by light microscopy.

Oter fibres, in addition ta the uree standad reference samles,

were inoculated intrapleurally into rats by Wagner et ai. (1973). Meso-

theliars occured in 18/32 animls injectd with a sanle of brucite

(nemlite, which may be contamnated with chrysotile), in 3/31 injectedwith a ceramc fibre, in 1/30 injected with barium sulfate, in 1/35

injected with glass p:der and in 1/35 injected with alumnium oxide. Nomesothelioms occurred in animls injected with a coarse glass fibre.

Wagner et ai. (1977a), in a series of exrinnts ta c~are thebiological effects of a pure, asbestos-free cosntic talc with those of

the suprfine chrsotile asbetos used in previous exprimts,inoculated 48 Wista rats intrapleurally with each of the two dusts.Eightee of those recei ving chrsoti1e developed nesothelioms, but no

rnsothelioms were seen in those gi ven talc.

Furer evidence of the imrtance of fibre diarter was provided

by Wagner et ai. (1977b) who reported on rats injected intrapleurally

with glass fibre (Table 17). 'Io sanles of glass fibre wee used, one

wi th a nean fibre diaiter of 0.12 llm and the other wi th a rædian

49

díãrter of 1.8 jJff. Four mesothelicrs were observed in 32 rats injected

with the finer fibre and none in those given the coarser fibre. Also, the

degree of nesothelial cell hyprplasia was rrre prononnced in the rats

injectd with the finer fibre. These results ~re OJrrarable with those

of the previous ~rimnt.Shabd et ai. (1974) report that when 20 mg Russian chsotile were

injectd intrapleurally 3 tins into 67 rats, 31 developed nesothelioms

wi thin 2 years.

Hater: ln groups of 50 haters given a single intrapleuralinjection of l, 10 or 25 mg chrsotile, 0, 4 and 9 ræsotheliansoccured, respectively; with 1 or 10 mg ansite, 4/50 haters develoPem2sothelian at the highest dose only. UICC crocidolite, give at adose of 10 mg induced ræsotheliom in 10/50 haters; a dose of

1 mg induced ræsotheliom in 2/50 haters; UICl anthophyllite

(10 mg) produced mesotheliors in 3/50 hamters (Smth & HUbrt,

1974) .

Rait: Intrapleural injection of 16 mg crocidolite into 13 rabbits

induced nesotheliors in 2 surivig 22-24 rrnths (Reeves et aL., 1971).

(d) Intratracheal injection

This technique has ben used ta study coarcinogenesis of chrysotile

asbetos with bezo(a)pyrene (Ba) in rats (IA, 1972; Pylev, 1972;

Pylev & Shabad, 1973; Salk & Vosame, 1975; Shad et aL., 1974) and

in haters (Miller et ai., 1965; Smth et ai., 1970).

Rat: Shabd et ai. (1974) shawed tht intratracheal injection of

2 mg Rusian chsotile on which 0.144 mg Ba was adsorbe (3 tins at

rrnthly inteals) or of 2 mg Rusian chsotile tother with 5 mg Ba

(single injection) prouced lnng papillom, epiderrid cacinom,reticulosarcomas or pleural nesotheliomas in 6/21 and 6/11 rats, res-

pectively, withn 9-28 months. No lnng tururs or nesotheliomsocured in 49 rats given 3 doses of 2 mg chrsotile alone or in 19 ratsgiven a single dose of 5 mg Ba alone, during, or up to, 28 rrnths of

observtion.

50

Ha."'ter: Smtii- et al. (197û) shCM tht anng 31 hatersrecei ving a total dose of 4.5 IT Ba plus 12 mg chrysotile over a perimof 12 weks, 7 developed pubrnar adenomas, 7, pulmnary cacinomas, 9,

tracheal papillan and l, a largeal papillom. No lung tUIurs were

obsered in 17 haters receiving chrsotile alone, and only 1 pulnnary

cacinom but 9 tracheobronchial papilloma were fonnd aTng 38 hamtersrecei VlIg Ba alone.

(e) Intraperitoneal admistration

M'use: Pott et ai. (1976) injecte 540 NM llce intraperitoneallywith 2 or 6 IT chsotile, crocidolii:e or glass fibre and observed rnso-

thelians. No nesotheliomas occued in contrls or in llce gi ven

haemti te .

Rat: Reeves et ai. (1971) gave i.p. injectons of 20 mg arsite,

crocidolite or chsotile into groups of 11, 13 ar 13 Charles River CD

rats, respectively. Thee peritoneal nesotheliomas were observd with

chrsotile, 3 with crocidolite and I1ne with arsite, after 7-17 nonths.

Maltoni & Anoscia (1974) injected 25 mg crocidolite intraperitoneal-

1 y in to 50 male and 50 femle 17 -wee old Sprague-Daw ley rats andobserved 65 peritoneal rnsothelioms, 31 in males and 34 in femes.

Pott & Friedichs (1972) induced peitoneal tunurs in wista rats

by i.p. injections of chsotile and fibrous glass. Tuurs were alsoobserved with crocidolite (Pott et aL., 1976). The dosage and results

after i. p. admistrations of several fibrous and granular dusts are

shaw in Tables 19 and 20.

After i.p. injection of pCderec chrsotile (fibre lengts, 99% -: 3llm,

93% -: 1 llm and 60% -: 0.3 i.), 0011 -milled for 4 hours, the latent period

for the induction of tunurs was found to be longer than after i.p.

injection of standard chrsotile (95% -: 5 llm). The rate of tUlur

occence after injection of chsotile was not distinctly influenced

by the addiuion of benzo(aJpyrene. ln another group, bezo(aJpyrenewithout asbstos induced tunurs in 10% of the anims. Histologically,

the tys of tUIurS obsrvd were connecte with strctues of the

51

LnNTable 19

'Iurs in aborrn and/or thorax after intraperitoneal injection of different fibrous

or granular dusts in ratsa

OUst Foi: Lp. Effecti ve No. of days Average Rats 'Iur typdose n i.r of before first suri val tir with(m:) dissected t urur of rats with turrs

rats tururs (days (%) ririafter injection)

~ri

i'rl~ rl 1

''; rl§

§Ulrl 1

t §ulQJ

~ § ~ §:5 ,,; 5,:i

8. ~ 1~ u ,,;

~'- " c:

~ (f Ul i£ Ul u ai ¡g al

uree Rhodesian f 2 37 431 651 16.2 4 2 - - l -

c:rysoti le" f 6.25 35 343 501 77.1 24 3 - - - -

" f 25 31 276 419 80.6 21 2 1 1 - -

" f 4 x 25 33 323 361 54.5 16 2 - - - -

" f 3 x 25 33 449 449 3.0 - - 1 - - -

s.e. s.e." f 4 x 25 37 400 509 32.4 9 3 - - - -

mi lled

Palygorscite f 3 x 25 34 257 348 76.5 24 2 - - - -

Glass fibres f 2 34 692 692 2.9 1 - - - - -

S + S 106

" f 10 36 350 530 11.1 2 2 - - l -

" f 4 x 25 32 197 325 71.9 20 3 - - - -

Gysum f 4 x 25 35 579 583 5.7 - - L L L -

Hemlite f 4 x 25 34 249 315 73.5 17 8 - - - -

Actinoli te 9 4 x 25 39 - - - - - - - - -

Bioti te 9 4 x 25 37 - - - - - - - - -

Hacitite 9 4 x 25 34 - - - - - - - - -

(precipi t.)

Haem ti te 9 4 x 25 38 - - - - - - - - -

(mineraIPectoli te 9 4 x 25 40 569 569 2.5 - - - 1 1 L

San idine 9 4 x 25 39 579 579 2.6 - L - - - -

Talc 9 4 x 25 36 587 587 2.8 1 - - - - -

Naei (control) - 4 x 2ml 72 - - - - - - - - -

£ From Pott ." (1976) !2 f, fibrous; g. granular; "- Not evaluated in turur rates

Table 20

Tuurs in abom and/or thorax after intrar-ritoneal injection of glass fibres,crocidolite or corudum in rats£

Out FOi: Lp. Effective No. of days Average Rats Tuur typdose numr of before first suri val tiir with(ff ) dissected turur of rats with tururs

rats tururs (days (%),.,.

after injection)~

,.~,. ,.

~,.

èui.ri Q)~,. 1 U

CJ

~ §

l, ~B ã §

U'

fi ~, 8 .ri §,0 U 'j .ri(f .ri '"

(j ~ ~ adJ Æ~ Ci rU"' Ul ui p. L~ u

Glass fibrest1N 104 f 2 73 421 703 27.4 17 3 - - 1 1

Il f 10 77 210 632 53.2 36 4 - 1 3 -Il f 2 x 25 77 194 367 71.4 47 6 2 - - -

Glass fibresMN 112 f 20 37 390 615 37.3 12 1 - 1 - 1

Crocidoli te f 2 39 452 761 38.5 12 3 - - 2 1

Corundum 9 2 x 25 37 545 799 8.1 1 - - 2 2 2

.£ Frari Pott et al. (1976); Q f, fibrous; g, granular; £. Not evaluated in turur rates

u,w

ui,t

Reference

A. ORA

Gibel At al., 1976

Wagner et ol., 1977a

B. INHTIONLynch et al., 1957

Table 21

Sllry of rrst relevant animl exrirnts

Findings

With asbestos filter material, 12/42animIs wi th malignat tururs(4 kidney carcinams, 1 lung carci-noma, 3 reticulum-cell 'saroomas,4 liver-cell carcinams)With talc, 3/45 rats with liver-cellcarcinOls2 liver-cell carcinOls in 49controls

2 gastric leiomosaroos, 1 in arat fed chrsotile and 1 in a ratfed talcNone in c."Ontrols

Pulmnary adenomas in 46% (58/127)of chrysotile-exsed group and in36% (80/222) of contrIs

Animl species

Groups of 50 L\listarats

Groups of 32 L.¡istarats

AC/Fi hybrid mice

Dosage

50 mg/kg l:/dayadmnistered inthe diet for life

100 mg/day on5 days/v.r for100 days over a6-rrnth pericx

150-300 millionpariCies/nù8-12 hr/day on5 days/we for17 rrnths

Ty of fibre

Asbestos filtermaterialoontaining 52.6%chrysotile,talc

Chrsotile,talc

Chrysotile

Referenæ

Gross iot n,~., 1967

Reeves "t ,l 1., 1971

Reves , ~ 01.'., 1974

l''agner ci iil., 1974

Reeve's, 1976

i"¡agner c' ,Il., 1977 a

U1U1

Findings 1 Animl species25/72 rats surviving 16 rrnths or longer 1 Ratsdevelope lting ti.rs (17 adenocarci-noms, 4 squus-cell carcinomas, 7fibrosarcas)No such tururs in 39 =ntrols

2/31 rats developed carcinomas of th 1 Ratslung after crocidolite expsure5/40 rats develope adenamtosis afterchrysotile expsure

5 lung carcinams with crocidolite,2 lung carcinoms and 1 pleural meso-the1ioma with chrsoti1e and 2 pleuralmesotheliom with arsite

Asbestosis produced with allfibreslung cacer mesotheliam11/146 1/14616/145 2/14516/141 4/14117/137 4/137

typs of

30/144 0/144

fibrears i teanthophy Hi tecrocidoli te

chrysotile(Canadian )

chrsoti le(Rhodesian)

With crocidolite, 14% incidence ofmalignt tururs of the 1ungWith chrysotile, 5% incidence ofmalignant tururs of the lung andmeiastinum .Í'lith arsite, 5% incidence of malic:ttumurs of the 1ung and pleura

1 adenocarcinom of the 1ung wi thsuperfine chsoti1e in 24 ratsexpsed for 12 rrnths

Groups of 69 CharlesRiver CD rats

CD I,,istar rats

Rats

CD I,,istar rats

Dosage

80 mg/m3, 30 hrs/week

49 mg/m', 16 hrs/v.k for 2 years

5 irq/m 3, 4 hrs/

day on 4 days/v.k for 2 years

12 mg/m3, 7 hrs/day on 5 days/v.ek for 1 day, 3,6, 12 or 24 rrnths

50 mg/m3, 4 hrs/dayon 4 days/v.k for2 years

10.8 mg/m3, 7.5 hrs/day on 5 days/weekfor 3, 6 or 12 rrnths

Ty of fibreChrsotile

Crocidoli te,chrysoti le,

arsite

Crocidoli te,

chrsoti le,amsi te

5 urccasbestos sam1es

Crocidoli te,

chrysotile,ar i te

Chrsotile

lJmReference

C. INTRALEURDonna, 1970

Reeves cI al., 1971

Reeves eL ùZ., 1971

Staton & Wrench, 1972

Pylev & Shabad, 1973

Shabad i: :i., 1974

Smith & Hubrt, 1974

Wagner c t ni., 1977 a

Wagner c; ù i., 1977 b

Findings

I-EsothelioITs

1/3 mesothelioIT with crocidolite,2/12 mesothelioITs wi th chrysotile

2/130 mesothelioITs

MesothelioITs in 60% of rats

Mesotheliomas in 37.5% of rats

31/67 mesothelioITs within 2 years

Chrysotile, 1 mg, 0/50 mesotheliams10 mg, 4/50 mesotlleliams25 mg, 9/50 mesothelioITs

Amsi te, 1 mg, 0/50 mesotheliams10 mg, 4/50 mesothelioITs

Crocidolite, 1 mg, 2/50 mesotheliams10 mg, 10/50 mesotheliams

Anthophylli te, 10 mg, 3/50 mesotheliams

18/48 mesoG~elioms Wie1 chrysotile,0/48 mesotheliams with talc

61% mesotheliam with crocidolite,36% mesothelioITs with amsite,34% ~sothelioITs with anthophyllite,30% mesothelioms with Canadian

chrysotile,19% mesotheliams with Rhodesian

chrsotile

Animl species

Spragu-Dawley rats

Rats

Rabit

Osborne-Medel rats

Rats

Rats

Groups of 50 hamters

Group of 48 vlistarats

CD vJistar rats

Dosage

67 mg

10 mg

16 mg

40 mg

3 x 20 mg

3 x 20 mg

Single dose of 1, 10or 25 mg chrysotile,1 or 10 mg arsite,1 or 10 mq crocido-lite, or 10 mganthophyllite

20 mg

20 mg

Ty of fibre

Chrysotile,arsi te,crocidolite

Crocidoli te,chrysotile

Crocidoli te

Crocidoli te,ars i te ,Rhodesianchrysotile

Russian chry-sotile

Russian chry-sotile

Chiysotile,amsite,croidoli te,anthophyllite

O1rysotile,talc

5 UICCasbestossamles

Referenæ

O. INlRATRHFSmith et al., 1970

Shad et al., 1974

E. INTRERlTONEReves et al., 1971

Pott et al., 1972

Mal toni & Anoscia,1974

Pott et al., 1976

F. SUBtJANOUS

Pott et al., 1976

ui..

Findings

7 pul.nary adenams, 7 pulnarycarcinams, 10 tracheobronchialpapillams amng 31 hamters

Lung papi11omas, epidenrid carcinamsreticulosarcoma, pleural iæsotheliomasin 6/21 and

6/11 rats within 9-28 months

After 7-17 rrnths,3/11 peritoneal iæsotheliams wi thchrysotile,3/13 peri toneal iæsotheliams wi thcrocidolite,0/13 peritoneal iæsothliams wHhamsite

40% tururs

31/50 mesothe1iom in males,34/50 n~sothe1iomas in fem1es

16% tururs77% tururs81% tururs55% tuirours39% turrs

1/33 loc tl.urs

Animl species

Hamters

Rats

Chrles River co rats

íoJista rats

Groups of 50 Sprague-Oawley rats

íoJistar rats

íoJistar rats

Dosage

12 mg chsotile +4.5 mg benzo(a )pyrene

2 mg Russian chryso-tile with 0.144 mgbezo(a)pyrene 3tims at rrnthlyintervals2 mg Russian chryso-tile + 5 mg benzo-(a )pyrene (singledose)

20 mg

100 mg

25 mg

2 mg6.25 mg25 mg100 mg2 mg

75 mg

Ty of fibre

Oirysotile

Rus sianchrysotile

Aisi te,crocidoli te,chrsotile

Chrsotile,mi11ed to99% .ç 3 ~m

Crocidolite

ura: Rhodesianchrsotile

urcc crocidoli te

uree Rhodesianchrsotile

abonùl wall, incltring th serosa, an, in isolated cases, with thseof the intestinl wall (Pott et ai., 1972).

(f) Subtaeous admistration

Rat: Pott et ai. (1976) observed a single local turur after s.c.

admistration of 75 mg Rhodsian chrysotile ta 33 Wista rats.

3.2 Otr relevant biological data in animls

(a) Retetion

The penetration and clearance of radioactive UI(X crocidoli te hasbe sttried in rats. Of 35% of inaled crocidolite deposited onto

respiratory tissues, approxitely half lodged in the upper aii:ys and

was cleared to the gastrointestinal tract within an hour. The reminderin lnngs and trachea was reduced after 30 days ta 73% of the initial

value (Evans et ai., 1973).

The retention of different typs of asbestos in rats follCMing

exsure ta the sam concentrations of respirable oost was describe byWagner et ai. (1974). For the amhilxÜes, there was a simlar pattern

with an alnst proportional increase of lnng dust with dose. Much less

dust was found for the chsotiles, and no increase of dust content wa

shown in the lnngs. Out in th lungs of animls wi th 6 nonth' exsurehad be partially cleaed 18 nonths after the inlation period. Abut74% of the ansite and crocidolite and 41% of the anthophyllite were

elinated. The elimnation rate of chsotiles could not be determed

exctly, because of their lowoccurence in the lung (Fig. 1).

(b) Migration of fibres fro sites of entry

The qustion of whethr asbestos fibres can nove frorn their site ofprimry depsition in the bo and irruce cacer at other sites is stilla vexng one. Volkheiir (1973, 1974) and Scheibr (1974) have reportd

that paricles and plant fibres ingeste by expriintal animls and maca penetrate the wall of the gastrointestinl tract and be tranported

thoughout the boy, possibly appearing in the urine. Westlake et ai.(1965) fed a diet containg 6% chrsotile to rats and reportd that the

58

Weight of dustin lungs (mg)

15

10

5

o

o

Figue 1. Effects of inlation of asbestos in rats fl

--After removalfrom exposure

- -

Chrysotiles

3 6 12

---------------~24

1*

10000 20000Cumulati ve dose (mgl ml hours)

30000

a- From Wagner et al. (1974)

~o

Time (months)

59

ariÍ1nals had fibres in t.1-e ~.!all of t.1-e oolon. Cuingha'T & Pontefract(1973) perforr a simlar exrimt and reported tht asbestos fibresappeared in the bloo ar various tissues. The rrre recent report by

Gross et ai. (1974) concluded, however, that there was no satisfactory

evidence fro their study of transmgration of fibres outside the gastro-intestinal tract.

ln studies in which chrysotile, lablled intrinsically with radio-

active trace netals by neutron irradiation, was injected intrapleurally

into rats, Holrs & MJrgan (1967) fonnd evidence for passage of a small

annnt of the fibre from the pleural cavity and lnngs into such other

organs as the li ver: after intrapleural inoclation of chsotile intorats, as much as 22% of the admistered dose was fonnd later ln the

liver (M:rgan et ai., 1971). ln a simlar exrinnt, M:rgan et ai.

(1971) reported that a poulation of radionuclides, consistet with tht

exted on the basis of the labiie: chrsotile, was fonnd in the heart,

lnngs, diaphragm and chest muscles.

Kaachaova et ai. (1969) and Friedichs et ai. (1971) found sorevidence for moVeInt of asbestos fibres from an intraperitoneal site

of injection into various tissues of the rats us. The latter groupof investigators reported that rrvemt wa inversely related to thelengt of the fibre, becomig essentially zero for fibres 20 llm or nore

in lengt.Intravenusly-injected asbestos is found mostly in the liver and

lungs in rats (Cuingham & Pontefract, 1973); chrsotile injecte

intravenously into pregant rats crossed the placenta and appered in

the livers and lungs of th foetuss (Ctgha & Pontefract, 1974).

(c) Association of scaring with turur developænt

ln early exrirnts, it was dernstrate tht gunea-pigs and

rrnkeys exsed to the four corcial typs of asbestos develope

fibrotic lesions of the lnng and pleura simlar ta those see in hmncases of asbestosis (Holt et aL., 1965; Vorwald et ai., 1951; Wagner,

1963). ln more recent exprirts, this findighas be confi:r in

rats and haters (Smth et ai., 1970; Wagner et ai., 1974).

60

(d) Oter e.xrÌIntal svsta~ ~Several authors have dem::mstrated the cyotoxici ty of asbestos

fibres in in vitro system. This toxicity is thought to be due to the

interaction of fibres with plasm meranes. Beck & Bruch (1974) ar

Beck et ai. (1971, 1972) investigated the effects of chrysotile and

glass fibres on L-cells and peritoneal and alveolar macrophages in vitro.

Thy dernstrated, by electron microscopy, inconplete phagoctosis,

disturbed penæability of cell meranes and loss of enzyr activity.Powdered chrsotile or glass fibres had more effect on the cells th did

nnp:dered fibres.

Allison (1973) detected tv. typs of cytotoxic effect: an early

effect due ta interaction with the plasma rrrane an a late one due taan interaction of ingested asbestos particles wi th the rrranes aronndseconda 1 ysosars . Interactions of asbestos particles wi th macrophages

and iæsothelial cells are sInlar, but there is less effect with fibro-

blasts. Asbestos was found to be cyotoxic for malignt P388Dl cells,

which have macrophage-like characteristics (Wade et aL., 1976).

The induction of interferon by influenza viru was depresse inasbestos-treate monkey kidney-cell nonolayers. This also suggests tht

asbstos fibres act on cell rrranes (Raon & Eckert, 1976).

Sincok & Searight (1975) reported tht chrsotile and crocidolite

asbestos dusts in concentrations of 0.01 ID/ml induced chrorrosomal

abrrations in cu tured Chinese hamter cells; these chages were not

observd wi th glass J?der or glass fibre of 2 jJ diarter. Charsolabrrations were founin 30% of ceiis exsed ta glass fibres of lessth 2 llm dianter (Sincock, 1977).

61

3.3 Case relXrts and eDidemoloaicai studies~ ~ J(a) Occupational exsure to a:rcially exloited sources

Historical backgrnnd

ln 1935, over one-half a centur since asbestos bean to be used Üiindustry, susicion of an association betwen asbetosis and lnng cancer

was reported by Lynch & Smth (1935) in th USA and by Gloyne (1935) in

th UK. Abut 10-15 years later, case reports of neplasr involvingpleural tururs associated wi th asbestos exsure appered (W=dler,

1943a,b; Weiss, 1953; Wyers, 1946), an a peritoneal turur was

repJrted in an asbestos worker by Leicher (1954). Epidemological evidence

fro 0011 (1955) shCMed a ten-fold e.xcess risk of lnng cacer in those UK

asbestos textile w.rkers who had ben emloyed before 1930 an for 10 ormore yeas. ~sothelioms were repJrted to occu in llers of croc idol i teand in non-nning population in the region of the llnes (Wagner et a i. ,1960). Simlar findings v.re reported in th USA, where lung tUlurS and

meotheliomas were reportd in asbestos workers (Macuso & Coulter, 1963;

Selikoff et ai., 1964). Possible variations in risk with different

tys of fibre were rarely considerEr in the early reprts: hCMver,

Selikoff et ai. (1965) did sa in one paper. ln 1964, theUIOC Wbrking

Group on Asbestos and Cacer (UICC, 1965) mae a numr of recations,

an in the last decade there has ben an exansion in the num ofepidemological stu:ies in may pars of the wor ld.

Epideological studies

Ci) Lung cacer, pleural and peritoneal nesatheliomMied tys of fibre: ln rnt indus trial enterprises different

typs of fibre ar usd, so expsures to a single asbestos typ are

unusual. MJrtlity studies of asbestos maufacturing, insulatig an

shipyard workers have provided the nost concrete evidence concerng anassociation betwn lnng cacer, pleural and peritoneal meothelioms

and exsure to asbestos. Reports have coræ frorn several countries:the Federal Republic of Gerny (Bohlig et al., 1970); ltaly (Ruina

et al., 1972); The Nethrlads (Sti.hius, 1971); th UK (Elns &

Sinson, 1971; Newhous, 1969); and the USA (Selikoff, 1976a; Selikoffet ai., 1964, 1970).

ó2

The study of Doll (1955), continued by Knx et aL. (1968) and

then by Peto et aL. (1977), has dernstrated tht there is a 2-3-fold

excess of lnng cacer in those workers first enloyed betwn 1933 and

1950 and in those first exsed in 1951 or later. A seven-fold excess of

lung cancer was fonnd in a group of insulation v.rkers exsed to chso-tile and ansite but not to crocidol:Lte (Selikoff et ai., 1973). Enter-

line et ai. (1972) reporte a 4.3-tirs increased risk of respiratory

cacer rrrtali ty aTng maintence service workers and al. 7 -tiis

increased risk aTng production workers who had reached retirernt age

and had ben exsed to rned asbestos fibres. Arng nen in the asbestoscent industry with rned exsur.s to crocidolite and chrsotile, therate was 6.1 tirs tht excted (Enterline & Henderson, 1973).

Enterline et ai. (1973) suggested tht there is no direct dose

response for respira tory cacer belav 125 mppcf-years, but this sugges-

tion was challenged by Schneide (1974).

Haries (1976), De Lajare et ai. (1976) and Biava et ai. (1976)

have shawn that there has been a steep rise in the incidence of nesothe-

lians since 1962. Edge (1976) reportaì that shipyard workers with

pleural plaqus who had rned exsw:-e to asbestos (wi thout evidence ofpu1na fibrosis) have a 2.5-tirs increased risk of developing caci-nan of the bronchus, when cciared 'vi th the general population; furer--

nore, 17 of 70 deaths amng th 235 ræn nnder observtion betwn 1970-74

were dæ to ræsothelian. ln a second group of 156 ir the sar author

sho~ a 2. 6-fold increased risk of cacinors of the bronchus in fonrrshipyard workers wh had pleural plaqus as conped with controls wi thoutpleural plaqæs.

In a study of 2 cohorts of sheet-rtal workers who had worked

for 5 or nore years' be~ 1950 and 1970 in the construction industr andwho had iæasurable and llxed asbestos exsure, Cooper et aL. (1975)

obsered an excess of deaths due ta maignat neoplas (24.8 and 26.5%

of total deaths in the 2 cohorts, respectively, cced ta 19.1% ofdeth in a group with deth claÍ1; 14.6% and 16.2 would have ben

excted in US males in 1959 and 1967, respctvely). This

increase was attributed largely to an excess of maliC)ant tUfurs63

of the respiratory tract. Of the 307 df'-rths in the first cohort, the 32

lnng cancer deaths ~re significantly in excess (1. 7 tins) of the numrexcted. One pleural mesothelian was observd.

ln a study of 689 asbestos workers exsed ta mied fibres for

20 years and observed during 1959-75, 35 lnng cancer and 26 pleural or

Peitoneal nesothlian were observed aIng 274 deaths (Nicholson et ai. ,

1977) .

Newhouse (1969, 1973a) and Newhouse et al. (1972) showed that

the cacer risk following mied exsure of factory workers to chrso-

tile, arsite and crocidolite is dose related. Those yiorkers reported

ta have had heavier exsures (as judged by their occupations) showed

an excess of lung cacer (6-fold for ræn, l2-fold for waæ) after 15years, 'Wereas those wi th moerate or low exsures requred 25 yearsta demonstrate an excess. The rate of ræsothelioma increase wi th baththe severity and th lengt of expsure; 22 nesothelioma were observed

in those exsed for less tha 2 years (Newhouse & Berry, 1976).

Additional confirrtory evidence of the association bet~ennesothelian and past exsure to asbestos coræs fro may institutes,depants of patholog and cacer registries in, e.g., Australia(Milne, 1976); the Federal Republic of Germy (Han et aL., 1974);Finland (Nuren, 1975); France (De Lajare et ai., 1973); the GeDeratic Republic (Stur & Bittersohl, 1975); Italy (Gobbato & Ferri, 1973;

Putoni et ai., 1976); The Netherlands (Zielhuis et ai., 1975); South

Africa (Webster, 1973); and the UK (Greerg & Lloyd Davies, 1974).

These studies have shav an association between asbestos and ræsotheliom,

so with exsures as brief as one day; hCMever, in approximtely 15%

of ræsotheliom cases no evidence of exsure to asbestas could be

ascertined. Thee studies (Greerg & Lloyd Davies, 1974; McOnald

et ai., 1973; Newhous et ai., 1972) showed a por correlation betwee

certified cause of death and histalogical diagnosis of ræsotheliom.

The reported ratio of pleural ta peritoneal t1.urs varies

widely in different stuiies; peritoneal tUTurS appar to be assoiatedwith heavier exure (Newhous et ai., 1972; Selikoff et ai., 1970).

64

Am::mg a nur of ocupationally exsed grups studied, awroxLmately

5-10% of death have be due to nesothelicm (Gilson, 1973; Hand& Selikoff, 1973; Selikoff, 1976a). tbre recently, hcever, an estimtehas projected tht the death of bet'n 8-11% of fOIlr asbestos

workers frorn a particular factory in the UK will be due to nesotheliom

(Newouse & Berry, 1976).

Maischig et aL. (1977) fonnd that 58 out of 201 me with

lnng cancer admtted to a thoracic surgical centre gave, after careful

qustioning, a history of expsure to asbestos, cored with only 29of the matched contrls, al though none were ostenibl y 'asbestos workers'

and none had evidece of asbestosis.

Analyses of lnng paenchyml tissues obtaned frorn ne erloyedin the Canadian chrsotile nùing industry who had be clinically diag-

nosed as asstotic have sho. the presence of trerlite and other

arhile fibres, often in excess of chsotile (Pooley, 1976). The

analyses illustrated tht the presence of arhibole fibres in comrrcial

chrsotile material rnay be invol ved in the etiolog of subeqent diseasefro expsure to dust arising frorn chrysotile materials.

Individual typs of fibre

Crccidolite: ln 1956, Wagner staed investigating the cccur-

rence of pleural rnsothelior in th crocidoli te nùing areas of the

North-west Cape Province in South Africa. It was sho. tht thse

tururs occurre in the non-miing population living in the vicinity aswell as aing nen working in th mines, lllls and in the tranporttion

and hadling of the fibre. Asbestosis was present in 8/33 caes. Thlatent period bet~ first exsure and clinical rection of the

turur was long - a Ilan of 40 years (Wagnr et ai., 1960). Subseqtsurillance of the llning population in all th asbestos-producing areas

of South Africa has deinstrated tht nesothelians ocur chiefly in

the crocidolite nùing areas of that conntry (Harington et aL., 1971;

Webster, 1973). The miing of croidolite in north-west Australia has

be assoiate with nesothelians (McNulty, 1962). Jones et ai.(1976) haVe reprted a high incidence of nesotheliom aing \\ne whoworke wi th crocidoli te in a factry proucing gas-nask canistes duringWOrld War II. 65

Chrsotile: McDnald et aL. (1973, 1974) reIXrted that theoverall death rate aTng 11,572 v.rkers barn betwee 1891 and 1920 and

observ from 1945 onwards and EIlo:(ed in the drrysotile mies and OOllsof Quebc province was lower thn that for the province as a mole.

Howver, an increased risk of lnng cancer was found. The authors

considered that those IDn who had ben most heavily exsed to the asbes-

tos dust showe abut a 5-fold risk COared with that of those leastexsed. Of 3270 deaths that had occured in this group up ta the endof 1969, 134 were due ta respiratory cancer, 129 of which were lnng

cancer and 5, pleural IDsotheliar. More recently, the authors (Mcnald& McDonald, 1976) have observed 3938 total death arng males up ta 1973,

of which 224 were due to lung cancer and 7 ta rrsothelioma. The authors

suggest that the nesotheliom nortlity in the Quebc chrysotile industry

as a mole was greater tha that excted on the basis of regionalnortality data. The ratio of lnng cacer deaths to all death ocingin the four years 1970-1973 is 14%.

Kogan et ai. (1972) investigated the cancer mortality amng

workers in asbestos mining and lllling industries betwn 1948 and 1967.

The total cacer rrrtli ty rate aTng v.rkers was 1.6 times higher than

in the general male population; for ferle v.rkers the rates were 0.8

for. those in mines and 1.3 for those in OOlls. The lung cancer riskfor male miers and OOllers was tw tins that of the general male popu-

lation. For femles in llnes and OO1ls the risks were 2.1 and 1.4 tirs

tht of the general ferle population, resPeively. For those v.rkers

over 50 years of age, the lnng cancer risk was greater: for IDn in

rning, 4.9; those in milling, 5.9; for w:n in nùng, 9.5; and forv. in milling, 39.8 tins tht in th general population. No neso-

thelioms were report. The numrs of Peple in the study populationswere not reported.

Wagoner et ai. (1973) reported on the cancer risk aing a cohort

of workers in a major maufacturing conplex utilizing predominantly chr-

sotile asbestos in texile, friction and packaging products. An excess

of respiratory cancer ocured aing asbestos workers in each duration-

of-eloymt categry dcm to and including 1-9 years. They obsered

66

a statistically signifiænt starrard rrrtlity rël-tio of 122 for all

ma1ignant neoplasm and 244 for malignant neoplasm of the respiratory

system. The asbestos workers in this sttry were located in an area of

prednatl y Dutch Amsh population wi th known low freqencies of

sirking .

Enterline & Henderson (1973) found that for retired nen who

had worked as prcruction or mainteance erloyees in the asbestos

industr and who had reache 65 years of age, those who had been exsedonl y ta chsotile had a respiratory cace risk 2.4 tims tht expcted.Arng ITn within the asbestos Cemnt industr exsed only to chrsotile

a 1.4-fold excess of respira tory cacer was found. Of 822 deaths, for

which 802 death certificates were fonnd (including those for v.rkers

exsed ta ansite or mixed fibres), only one mesotheliam had been

recorded (Enterline et ai., 1972). ln contrast, a subseqent investi-

gation by Borow et aL. (1973) fonnd 72 cases of nesothelian in one plant,

where chrysotile was the main fibre used. The discrePaCY may have bendue to nethodlogical variations; for instace, Enterline et aL. (1972)

had limted their investigation ta nen of age 65 or over, while may of

th nesotheliom cases reported by Borow et ai. (1973) had died before

that age.

Arsite: Exures to arsite in a factory maing insulation

materials were reported by Selikoff (1976a). Ten nesotheliomas were

fonnd, an there was an increased risk of lung cance in workers followed

up for 20 years or longer. The excess lnng cancer risk in the ansite

workers was shaw to increas with duration of erloyrnt. There was a

3.87-fold increase in lnng cancer amng those with less th thee

IInths' erloymt.ln a retrospective study of 914 men who had v.rked for various

period of tin during hTorld War II in a plant maufacturing inulating

materials from amsite for the US Navy, Seidm et ai. (1977) reported

that the group of 65 me who had worked for less th 1 nonth had an

excess nortality from lnng cancer (but not from all cancers or all

causes) which beca discernle onl y 30 yeas after the exure.

67

Excess nortality fro lnng cacer and all cacers that shoed up after

progressi vely shorter intervals after th exsure was reportd in Iænmo had worked for period ranging frorn 1 nonth to nore th 2 years.

Anthphyllite: ln Finland, anthophyllite llning has benassociated with an excess lung cancer risk of 1. 4; the risk is 2.7 after

allowig for snking habits in workers wi th more than 10 years' exsure.

There was also a higher prevalence of dyspno and cough in the miners.No rnesothelians ~re fonnd (M=un et ai., 1974). The occurrence in

Finland of an unusuall y high incidence of pleural thickening and calci-

fication, as detected by radiographical an pathological sureys, has,hCMever, ben reported (Kiviluoto, 1960; ~ur, 1966).

(ii) Oter cacers : EpidanolOÇical studies have consistently

shCM an excess risk of othr cances, especiall y of th gastrointestinal

tract, following exsure to rned fibres (E1ms & Sinson, 1971; Enter-

line, 1965; Hamnd et ai., 1965; ~ogan et ai., 1972; Macuso & El-

Attar, 1967; Newhouse, 1973b; Nicholson et aL., 1977; Selikoff, 1974;

Selikoff et aL., 1964), to amsite (Selikoff, 1976b; Selikoff et ai.,1972b) or to chsotile (Wagoner et aL., 1973). However, such risks

have been less than that for lung cacers. Scheiderm (1974), analysingdata fro the literature, ca ta the conclusion tht 'increased exsure

ta inled asbestos particles leads ta increased digestive system cancer' .

Stell & Mcill (1973) found tht of 100 Iæn with squus-cellcarcinmas of the lary, 31 had know exsure to asbestos, cnedwith only thee in matched controls. Simlar associations have bereported by M:rgan & Shettigara (1976) and Shettigara & M:rgan (1975).

Newous & Berry (1973) fonnd tw cases of cancer of the lary (ICD 161)

in their cohort of over 4000 workes, canred wi th an excted incidenceof 0.4.

The incidence of oropharygeal cace also appers to be

increased aTng asbestos workers (Selikoff et aL., 1970); however, thse

cacers occ\l relatively rare1y in relation ta other asbestos cacers.

(iii) Multiple prin cacers: Multiple prin tUTurs have bereport in 5 shipyard workers exsed to asbestos; 2 had bath a lung

68

carcinom and a colon cacin and 3 had 2 distinct pulnar carcinoms

each (Oohner et ai., 1975).

(b) Snking and ocuptiona exsure to asbestosln irt studes of asbestos workers, snking haits have not be

knCJ. Selikoff et ai. (1968) first took acconnt of snking an

calculated that asbestos workers who snke had 8 tins the lung cacer

risk of all othr sikers and 92 ti.s the risk of non-snkers who did

not v.rk wi th asbestos. 'Iis stu:y has be continued an the datainterprete as being consistent with a multiplicative (SYergistic)

effect of the cacinogen, snking and asbestos (0011, 1971; Hand &Selikoff, 1973), a view suptrted by another study (Be et ai., 1972).

Sa of th abve studes and recent studies fro NIOSH (1977) and

of Maischig et aL. (1977) are consistet with th ocrrence of anincrease risk aTnq non-snkers, which is, hCMever, of a lCMer order of

magnitude. Snking ha not be found to be assoiated with an increaseàrisk of nesotheliau or cacers of the stanch, colon and rectum, which

oc wi th eq freqency aTng siking and non-snking asbestos workers.

(c) Non-ocutional exsure ta conrcially exloited sources

Househld contact ~ th asbestos is associated wi th an increaed risk

for iæthlian. Mesothelians have ocured in household contacts and

in non-ouptionally exed indviduas living in the neighturhoo ofindustrial sources of asbestos (Bohlig & Hain, 1973; Newhuse & Thæison,1965; Wagner et ai., 1960). Anderson et ai. (1976) have recetly reviewe

37 such cases of neothelian fro nine conntries and reporte 4 new caesaTng famly contacts of asbestos workers. Studes of the geoaphicaldistribution of cases of non-ocuptional nesothelioms in th UK over a

2-yea period indicate that th ne cases are nearly all fran areas inwhich thre has be a recoized indus trial source of asbestos (Greenbrg

& Lloyd Davies, 1974).

Results have ben reported aTng non-ouptionally exsed personsin Finland living where anthophyllite asbestos is mied. ln this study,

118 of the tota of 126 case of roetgenologically diagnse pleural

69

calcification, e..cludig those individuals with haerthorax, eryer andtubrculosis, lived or had lived in areas i.ately adjacent to asbestos

llnes (Kiviluoto, 1960). The results of this stu:y suggest a health

hazard due to anient coun ty exsure to asbestos.

(d) Exsure ta asbestifom minerals other th IIned asbestos

A nurr of fibrous mierals other than th asbestas varieties existin nature. Sone of these occu as natural contaants of roks and oreswhich are released during miing, lllling or proessing (See also sections

1.2 (a) and (b) and Tables 3 an 4). For examle, tac ffay be contamatedwith asbestifom (fibrous) trenlite, anthphyllite and chrsotile, in

total concentrations greater than that of the talc IIneral itself (Kleinfeld

et aL., 1973, 1974; Rohl & Lager, 1974). Excess deaths due to malig-

nancies have occurred in workr ex,sed ta aerosols during the llnig an

milling of these materials, in addition to pneumoniosis. Ninetee of91 deaths recorded were due to lnng carcinoma (9), pleural fibrosarcom

(1), peitoneal nesothelioma (1), gastrointestinal tract cancer (6) and

other cancers (Kleinfeld et ai., 1967). Asbestos disease stigmta have

been reported in association with fibrous talc exsure (Rohl & Lager,1974) .

These observtions serve ta highlight the imrtat qustion of a

relationship bet~n exsure ta asbestifom mierals (not asbestos perse) and the occurence of excess malignant disease. This problem is

global in scope and potentially imrtant. For examle, iron-ore depositsmay present such a problan. Wagner (1928) dennstrate tht the exensive

iron deposi ts of the southern hemsphere, prüduced as a resul t of bacte--rial action, are simlar in nature ta those iron deposits maing up the

Mesabi Rage in the US an to those fonnd in ranges the world over(French, 1968). Wagner emhasized that these iron formtions would

contain fibrous iron silicates; an fibrous silicates are indee scattered

thoughout these deposi ts and occasionall y occur in large foci. ln the

southrn hesphere, the se deposi ts have or are being mied for amhibleasbestos, including the crocidolite deposits of the Cape Province, the

ansi te and croidoli te areas in the Tranvaal in South Africa, the

70

ITsorite deposits in Mysore in southern India and the crocioolite in

W=stern Australia and in Boli via.

The Tranvaal iron fonrtion ls also exloited for iron ore itself

and was the man source of iron ore in South Africa. ln recent years,

th increased dem for iron ore has led ta the openg up of large-scalesurface mining of the baded ironstone in Sishen in South Africa (Webster,

1973) and the Harrsley deposit, Wester Australia¡ bath these deposits

are in the vicini ty of know occurrences of crocidoli te fibre. ln

nortern US, asbestas fibre has not ben exloi te frorn the ~sabi

Rage. Al though iron ore is mied along ths range, fibressimlar ta and in sone instaces identical with the anhibale asbestos

vaiety exloi ted in the southern hemsphere are fonnd. Thse are

inevitaly mied with the iron ore. Simlar problem exist with othr

ores. Recent ooncern abut the potential carcinogenicity of non-cxrciall y exloi te materials of an asbestos nature has be raised

wi th regard to these ores and assoiated amhible fibres.

"M2 air concentrations of amhile fibres in oorrities surronnd-

ing milling operations have ben reportd to range fro 2.6-8.9x 103 fibres/rn3. Chsotile concetrations in individual samles ranged

fran none deteced ta 10.4 x 104 fibres/rn3. Concentrations of as high

as 11 x 106 amhible fibres/rn3 of air were reported nea spcific point

emssion sources (NIOSH, 1977).

Sttries of coi ties in georaphica areas near these llning

operations, wh are exsed to amhile fibres in drinking-water (Ievyet ai., 1976¡ Hassan et ai., 1974), darnstrate no increased risk of

cacer as of 1971. HCMver, since these mining operations bean in

approxitely 1955, the period of obseration is insufficient to evaluctethe presence or absence of an associated carcinogenic risk.

Studies using X-ray diffraction, optical microscopy and electrn-

be instruntation have dennstrated the presence of cugtoniteand grerite (ansite) fibres in a hard rock gold mie (Det et ai. ,1976). A stud of nndergronnd miers in this mine has dernstrated a

3-fold excess risk of nortli ty fra respiratory cacer (Gillam et a i. ,1976) .

71

Yazicioglu (1976) has conducted a radiogaphic sury of 15,239

peple living aronnd the city of Diyarbair in sout-east Tukey and

found 389 (2.6%) with evidence of pleural calcification. It has long

been custCIry to paint the walls an floors of houses in this area wi tha ma terial easil y dug from local rocks. Samles of this material havebeen identified by the State Miing Investigation Institute in Anara a.scontaining chrsotile fibre as one of the consti tuents .

Pleural plaques have ben obsered in agricultural \'rkers engaged

ID growing tabac co on stony Itnntainous sail in Bulgaria; anthophyllite,

trerlite and sepiolite have been found in regions where endemc pleural

calcification occus (Burilkov & Badjov, 1970; Burilkov & Michailova,

1970, 1972).

3.4 Analyses of fibres in tissues

The physical characteristics of asbestas fibres that peetrate to

the lung Paenchym have ben studied by Tllrell (1965, 1972), who

dernstrated that fibre respirability was largely a fnnction of fibre

diarter (Timrell et ai., 1970).

Two kinds of data are relevat; Tllrell (1972) has shown tht

the croidoli te lled in N:rtern Cape Province and in Western Australia

is associated wi th a freqent occurence of pleural rrsotheliom. Thscrocidolite had thiner and shorte fibres than the croidolite or ansite

llned in the Transvaal Province, where fewer caes of pleural nesotheliomhave ben reported. It has ben proposed that the reported riskdifference may be attributale to the differing physical chracteristics

of the fibres (Lager et ai., 1974).

A study (Sebastien et al., 1977) concernIDg diarter and lengt

of 5000 asbestos fibres from the lnngs of 10 decased persons who had

been occupationally expsed ta asbestos showed that these were all less

than 0.5 llm in dianter. The proportion of fibres shortr thn 5 ll

ranged from 70% to 90%.

Nilrous asbstos fibres, ei ther ot chrsotile or amhible or bathtyps, have ben fonnd by electron rr:icroscopy in th lnngs of industrially

72

exsed nen (PCXley, 1972, 1973; FondÌJre & Desoorde, 1974). A qunti-

tati ve tOpJaphic study of asbetos fibres in the lung that ha bencaried out in 12 industrially exed men ShCMed that heavily expsed

cases wi th lung fibrosis and cacil1s have fewer fibres in the fibrotic

lov.r lobes than in the less fibrotic uppe lobes. The fibres were nostly

of the arhible typ. ln cases of lnng cacer without lnng fibrosis, a

higher concentration of asbestos fibres, ITstly of the chrsotile typ,

was clearly dennstrated in peripheral areas of the lnng (Sebstien et

ai., 1977).

Optical ar transmssion electron microscopic study of lung and

pleura revealed a preferential accumlation of chrysotile vers us arhiblefibres in the pleura; the nean length of the fibres was greater in the

lung and visceral pleura than in the parietal pleura, this being particu-

larly the case for the arhibles (le Bouffant et ai., 1977). There was

no relationship betwen the nurrical concetration of fibres in lung

parenchym and that in Paietal pleura. Ceerally, th concentration was

always less in pleura than in Paenc::iym; hCMever, the distribution of

chsotile microfibrils in the pleura was Ilt horeneous, an in sarareas high exmcentrations identical -to those in the parenchym could be

observed (Sebastien et ai., 1976b).

ln a series of studies in Londo::i (Pooley et ai., 1970), New York

(Lager et ai., 1971) and le Havre (Sebstien et aL., 1977), chrysotile

fibres or fibrils were dennstrate by tranllssion electron microscoy

in the lnngs of ITst consective autopsy cases.

Pooley (1973) fonnd tht the lrmgs of 93% of 120 mestheliom casesstudied had asbetos fibres visible by electron llcroscopy, as coaredto less than 50% of 135 cases obtained at raran autopsies. Higher

concetrations of fibres were observed in nesothelioma than in non-rrso-

theliom cases. ln mesothlioma cases th fibre typs were ei therarhible or chsotile, or ooth, but arhile Was predomiant; 11 non-

mesotheliom cases, chsotile fibres were predminant. ln the thee

cases of nesotheliom included in the study of Sebstien et ai. (1977),

the percetage of chrsotile fibres was from 44-97% in the peripheral

73

areas of the lung. The ratio of amhibole ta chrsotile has ben fonnd

ta decrease from the cetral toward the peripheral areas of the lnng

(Fondie et ai., 1977; Le Bouffant et ai., 1977).

Asbestos l:es have be found, by light microscopy, ln largenumrs in occupationally exsed individuals (Ashcroft & Heppleston,

1973) and by optical and electron rncroscopy ln th lnngs of ITt

adults who have lived in urba areas (Bignon et ai., 1970; Davis &

Gross, 1973; Oldham, 1973; Selikoff et ai., 1972a; Thomon & Graves,

1966). The numr of coated fibres in lnngs has ben comared in personswith and without lnng carcinoma. Meun et ai. (1970), who tcok intoacconnt cigarette consumtion, could find no significat difference.

D:niach et ai. (1975) found an increased incidence of asbestos

boies in men wi th stcmch cacer and in warrn wi th breas t cacer, butnot in lnng cancer cases. Contrasting observations with regard ta lung

were made by Warock & Churg (1975), who fonnd that lnng cancer cases had'nore asbestos l:es in their lnngs than those without lung cancer, even

though only one case had had knCM occutional exsure ta asbestos.

It has long ben knCM that inalation of other fibres may result inthe formtion of boies resemling asbestos boies (William, 1934).

Simltaneous studies by optical and electron microscopy in 18 lungs

from subjects with various degrees of asbestos eXfsure ShCMed that

light microscopy could identify 41-100% of fibres as coated, whereas with

electron microscopy only 10% of all fibres wee coated in subjects

heavily eXfsed and only 0.21% in subjects with rrerate exsure

(Sebtien et ai., 1977).

ln persans ocupationall y exsed to asbestos, smaller numrs ofasbestos boes or fibres than are seen in lung tissue have been fonnd

in exra-pulnary tissues, inclu:ing tonsils, thoracic and abmiallymh nods, pleura, peritoneum, liver, spleen, kidney and smlintestine (Gcin & Jagatic, 1970; Zielhuis, 1977).

74

3 . 5 Asbestos is

Asbestosis iS a progressi ve, irreversible lung disease caused by the

inhalation of asbestos dust and is characterized by diffuse intestinal

fibrosis. The pathological features have ben describd by Wagner (1965),

and radiological features defined by Gilson (1971). A combined patholo--

gical-radiological correlation has be nndertken (Caplan et ai., 1965).

Early refXrts of an association between asbestos dust expsure andpulina disease were gi ven by Muay (1907) in the UK, Hof:f (1918)

in Canada and Pancoast et aL. (1917) in th US. However, the first

conplete descriptions of asbestosis \-vere not made until 1927, by Cooke

(1927) and McOonald (1927) in the UK, and 1930, by Mills (1930) in the

us. Early studes led may investigators to conclu:e that peple expsedto asbestos dust developed the disese, , asbestosis', if the dust concen-tration were high or if their exsure were long (Beintker, 1931¡

Dreesse et aL., 1938¡ Fulton et ai., 1935¡ ~ravether, 1947¡ M2rewether

& Price, 1930).

As ta a relationship between asbestosis and bronchial carcinoma,

thre is at present no scientific docUIntation indicating that thse

entities are interrelated in any way other th that thy constitute

disease outcones that may be associated causally with expsure toasbestos as a corrm:m environrntal factor.

Reent refXrts (Edge, 1976¡ Martischnig et ai., 1977) support thehypthesis tht an excess of branchial cacinomas exists in groups of

Pesans exsed to asbestos without concomitat radiological sign oflnng asbestosis.

75

..0"

Table 22

Surry of studes of carcinogenici ty in hum populations

Reference Group and exsureFinding

A. CCUPA TIONA EXURHistorical studies

Lynch & Smith, 1935 JGloyne, 1935

W:dler, 1943a,b JWyers, 1946W:iss, 1953

leicher, 1954

D:ll, 1955

Wagner et al., 1960

Macusco & Coulter, 1963

Selikoff et al., 1964

Epidemological studiesLoog, pleura and peritoneumMixed typs of fibres

Knx et al., 1968

Newhouse, 1969 (UK) JBohlig et al., 1970 (FRG)Selikoff et al., 1970 (USA)Elis & Simson, 1971 (UK)Sturhius, 1971 (The Netherlands)Rubino et al., 1972 (Italy)

Selikoff et al., 1973

Suspicion of association betwasbestos and loog cacerCase reports of pleural an peritonealtumurs assoiated with asbestos

A peritoneal tumurLoog cancer

Mesothelionas

Loog cacer and rrsotheliar

Loog cacer and rrsotheliar

Lung cacer, pleural anperi toneal rrsothelioms

Loog cacer

-

Asbestos v;rkers

-

Asbestos textile workers emloyedbefore 1930

rtiners and non-rning populationAsbestos v;rkers

Asbestos workers

Asbestos textile workers erloyedafter 1933

Asbestos nanufacturing, insulationand shipyard workers

Insulation workers; chrsotile andansite asbestos expsure

Reference Finding Group and expsure

Newhouse 1 1973aNewhouse & Berry, 1976

De Lajartre et al., 1973 (France)Gobbato & Ferri, 1973 (Italy)Puntoni et al., 1976 (Italy)Webster, 1973 (South Africa)Greenbrg & Lloyd Davies, 1974 (UK)Hain r: al., 1974 (FRG)Nurnen, 1975 (Finlan)Stur & Bittersohl, 1975 (GOR)Zielhuis et al., 1975 (The Netherlands)Milne, 1976 (Australia) _Newouse e t al., 1972Selikoff et al., 1970

Gilson, 1973Hamnd & Selikoff, 1973Selikoff, 1976a

Newhouse & Berry, 1976

Enterline et oZ., 1972Enterline & Henderson, 1973

Cooper et al., 1975

De Lajartre et al., 1976Biava et (J.l., 1976Harries, 1976

Edge, 1976

Martischnig et al., 1977Peto et clÎ., 1977

Nicholson et al., 1977

Single typs of fibresCrocidoli te

Wagner et al., 1960

J

J

J

J

J

J

Respiratory cancer Retired production and maintenanceworkers in asbestos industry

Sheet-metal workers

Shipyard workersShipyard workersNaval dockyard workers

Shipyard workers

Asbestos workers

Lung cancer

~lesothelior

Carcinoma of bronchus

Loog cancer

Evidence of association betweenmesothelioma and past exsureto asbestos

Occupational expsures, in sorcases as brief as one day

Peritoneal tumurs associated withheavy exsures

5% to 10% asbestos workers 1 deathsdue to mesotheliaæ

8-11% asbestos workers' deaths dueto mesothelicm

Loog cancer-

Asbestos w:rkersAsbestos textile workers

Asbestos workersLoog cancer, mesothelioma

Pleural cacer Workers in mines, mil1s and trans-

porttion and handling of croidoli teand population in vicini ty of mines

....

..00

Referenæ Finding Group and exsure

Harington et aL., 1971 JWebster, 1973

McNulty, 1962

Jones et al., 1976

~sotheliowa Hining population of crocidoli temiest.liners of crocidoli teíbæn working wi th crocidoli tein WWI gas-msk canister factories

Mesotheliant1esothe lian

ChrysotileMcDonald et al., 1973, 1974 JMcDonald & McDona1d, 1976

Koganetal.,1972

Lung cacer, rrsotheliom Chrsotile mine and mill workers

Wagoner et al., 1973 Respiratory cancer

ílorkers in asbestos miing andmiHing, rrn and worrn

Workers in iænufacturing of textile,friction and packaging proucts,using chrysotile

t1en 65 years and older, retiredpr.oduction or waintenance erloyeesin asbestos industry expsed on1yto chrsoti le

í'lorkers at plant using chrysotile,aH ages

Total cancer, 1ung cacer

Enter1ine & Henderson, 1973 JEnterline et al., 1972

Respiratory canær

Borow et al., 1973 M2sothelian

Arsi te. Selikoff, 1976aSeidm et al., 1977

!1esothelian, lung cacer JLung cancer

Insulation workers in factory usingarsi te

Anthophylli teMeur et al., 1974 Branchial cancer, dyspnoea and cough Anthophy11ite miing er10yees

Reference Finding Group and exsure

Other cancers

Enterline, 1965Hamnd et aL., 1965Macuso & El-Atta, 1967Elms & Simson, 1971Kogan et al., 1972Newhouse, 197 3bWagoner et al., 1973Selikoff, 1974, 1976bSelikoff et al., 1964, 1972bNicholson et al., 1977

Stell & McGill , 1973

l-rgan & Shettigara, 1976

Newouse & Berry, 1973Shettigara & ~brgan, 1975

Selikoff et al., 1970

Dohner et al., 1975

B. SMJKING AN ASBESTOSe1ikoff et al., 19680011, 1971

. Beny et aL., 1972Harnd & Se1ikoff, 1973

C. NON-CCUATICN EXæURAnderson et al., 1976

Wagner et al., 1960Newhouse & Thæison, 1965Bohlig & Hain, 1973

Greenbrg & Lloyd Davies,

D. ASBESTIFORM MINERA

Kleinfe1d et al., 1967

..1.

Gil1am et al., 1976 Underground gold mines

Cancer of gastrointestinl tract Asbestos workers

-

J

Workers wi th exsure taasbestos

Larygeal cancer

J

.~sbestos workers

Oropharygeal cancerMultiple prim cacers Shipyard workers

JLung cacer Asbestos workers

iJ~'esoL '"e Ham

Fam1y mers of asbestos workersIndi vidua1s in neighburhoo ofindus trial sources of asbestos

New cases from areas wi th recogizedindustrial source of asbestos

Lung, pleural, peritoneal, gastro-intestinl tract cancers

Respiratory caner

Talc miners and millers

4. Conts on Data Reported and Evaluation

All commrcial form of asbestos tested are cacinognic in mice,

rats, haters and rabbi ts. ln mice, ræsotheliars were induced

following intraperitoneal injection of asbestos fibres. ln rats, various

typs of asbestos produced lung carc--noms and ræsothelicrs following

their inalation and ræsothelioms and sarcos follcwing their intra-pleural or intraperitoneal injection. The oral admnistration of asbestos

filter mate rial ta rats also resulted in an increased incidence of

tururs. M:sotheliomas were produced in haters and rabbi ts after

intrapleural injection of a numr of tys of asbestos fibre.

The size and shape of the fibres influence the incidence of tumurs;

fibres less than 0.5 llm in dianter are mre active in producing tururs.Glass fibres and nemli te of a simlar size can also produce rnsothelianas

follcwing their intrapleural or intraperitoneal injection in rats.

ln hurs, occupational exsure ta chsotile, arsi te, antho-phyllite and mixed fibres containing crocidolite has resulted in a high

incidence of lung cacer; a predcxninantl y trerli tic material lled with

anthophyllite and smll arunts of ch.rsotile has also caused an increase

incidence of lung cancer. May pleural and peritoneal ræsothelicrs haveben observed after occupational exsure to crocidolite, arsite and

du:ysotile. An excess risk of gastrointestial tract cancers has ben

dernstrated in groups expsed occupationally to arite, chrsotile or

rnxed fibres containing crocidolite. An excess of cancers of the lar

was also observd in expsed workers. ~sotelioma also occu inindi viduals living in the neighburhoo of asbestos factories and croci-doli te mies and in household contac-ts of asbestos workers.

Occupational expsure to asbestos may occur during the rning of

fibrous rnnerals, as well as of llnerals ered in rocks, which may

contain asbestifonn fibres as a contamt.

Bath cigarette srking and occupational exsure ta asbestos fibres

independently increase lung cancer incidence, but vmen they are present

together they act in a multiplicative fashion.

80

The general pop.ilation may also ne e..sed to asbestos fibres in

air, beverages, drining-water, fooÓ and pharceutical and dentalprepaations and by consumr use of asbestos-containing products. The

presence of asbestos and asbestiform minerals from natural sources in the

envirorunt, other th ITes or quarries, has only recently shaw itselfto be a further potential problem.

At present, i t is not possible ta assess whetbr there is a levelof exsure in hurs below which an increased risk of cacer would not

occu .

81

APPENIX A

Th criteria for the evaluation of the carcinogenic risk of chemcals

to ma ~re estalished at a nur of neetings held prior to the publi-cation of Volur 1 of the IA Monograph series. All volurs published

since that tiI have followed essentially the sar fornt and are based

on the sar criteria. working Groups have ben limted to the assess-

nent of published data, on whch the final evaluation in tenn of carcino-

genic potetial is based. ln order ta ensur, hCMever, that the rrnoaphs

will continue to provide accuate and exensive evaluations in changing

circutaces, i t has be decided te) O)nvene a vlorking Group to review

th criteria used up nntil now.

The present WJrkig Grup, convened to evaluate asbestos, felt,howve, that in view of the imrtace of this substace, this nonograph

should also present a qutitative evaluation of the future scope of th

problem in term of society as a whole. Such forecasts are depedent on

seveal variables v.ich cat be predicte with certainty.

wi thout inl ying disagreet wi th the views of the WJrkig Group,

the Director of IA has reqsted tht this section appear as an

Appedix to the ma tet of the nonogaph.

SCOPE OF TH PROBLE RETE TO ASBETOS EXOSUPE

ln the first half cetur of rrler comærcial us of asbestos

(1878-1927), there ~re only sporadic reports of associated health risks,

and these ~re concerrd wi th pneurconiosis, .in paicular asbestosis(Coke, 1927). During those yeats the us of this versatile ma.terialexanded greatlYi with few precautions agaist expsure. ln spite of the

fact tht the hazards fro expsure to asbestos dust had ben clealy

defind by M2rewether & Price (1930) in the UK, by Dreesse et ai. (1938)

in the US and by Nordm (1938) in C'iey, inufficient action was sub-

sently taen. By the tiI the cancer potential had been recgnized and

defined (1935-1960), asbestos had perrated muh of noer indust.i,

82

and, indeed, nrern society, v,,'it.i- t.i-oU5¡ds of products beng ITBl1ufac-tured an utilized thoughout the world, in circumtances tht we now

nnderstad were inadeqte for the control of occuptional disease,includng cacer. As a result, we a"'e now faced with a double diler,

of how to deal with the conseqnces of previous inttention and error, in

tenn of hum disease, and of how to avoid furer exsure v.ich could

produce disease in the future.

The results of failures in the pat spur efforts for control (See,

e.g., Senior ~dical Inspector'_s Advisory Panel (1968) J. In may sttries

of groups of asbestos v.rkers, for examle, approxitely 20% of alldeaths are the resul t of lung cancer, thee-qrs of which are attri-butale ta their v.rk with asbestos (Selikoff, 1976b). Arng suc groups,

pleural an peritoneal ræsotheliomas have becone ccn¡ estimtes for

certin groups suggest that as may as 7-11% may die of the se diseases

(Newhouse & Berr, 1976), which othei:wise occur only rarely. Excess

incideces of gastrointestinal, largeal and oropharygeal cancer will

claim furer lives. There are few accuate estimtes of the numrs of

persons at risk from expsure to asbestos in the various countries of

th v.rld. Attets ta do so have be made in th US (Wagoner, 1976),

and it is sobering to realize tht there are now in the US approxitelyone million nen and wa who work regularly in maufactuing asbestosproducts or who were so emloyed in the past. Should the foregoing

estimtes hold for them as ~ll, SaT 200 thousand death froID lung

cancer and 50 or nore thousand death froID nesothelicrs will occur

(See also Newhouse & Berry, 1976). However, ta the extent tht we fail

to control further exsures, these will be nnderestimtes of the ocup-tional cancer incidence.

Another factor tht could lead to thir being nndeestimtes is that

such figues may not incltre cancers that result froID th mining and

lllling of asbestos or fro indirec occupational exsures (as in theshipyard and construction industries), fran a num of specific uses ofasbestas materials (as in brake repair and brake matanace work) , or

from paa-occuptional exsure or uncontrollable consl.r use of asbestosmaterials ¡ nor do they inchrle cacers that will resul t frai household

83

contact or neighburhoo exsures. Indee, no population exsed ta theindustrial use of asbestos has escap2d this hazardi it is also likely

that every countr in the \\rld has exprienced this public health

problem .

84

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EVALUATION OF CARCINOGENICRISK OF CHEMICALS TO MAN

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