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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
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tJ () (!-~ '¡ :-.L Ul .L
~ ~ x
u i: ~
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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
5. References
Allison, A.C. (1973) Exrimtal ræthods. eell and tissue culture:effects of asbestos paticles on macrophages, ræsothelial cellsand fibroblasts. ln: Boovski, P., Gilson, J. C., Tllrell, V. &Wagner, J. C., eds, Biological Effects of Asbestos, Lyon, InternationalAgency for Research on Cacer (!A Scientific Pulications No. 8),pp. 89-93
AIrican Water Works Association (1974) A study of the probler of asbestosin water. AIr. Water Works Ass. J., Septemr, 1-22
Anderson, H.A., Lilis, R., Daum, S.M., Fischbin, A.S. & Selikoff, I.J.(1976) Household-contact asbestos neoplastic risk. An. N. Y. Acad.Sci., 271, 311-323
Asbestosis Research Council (197la) The l'1easurernt of Airborne AsbestosDust by the Merane Filter M=thod, Technical Note l, wndon
Asbestosis Research Council (197lb) out Saling Procedures for Use withthe Asbestos Relations 1969, Technical Note 2, London
Ashcroft, T. & HeDDleston, A.G. (1973) The optical and electron microscopicdetennnation of pul:nar asbestos fibre concentration and its relationto the hur pathological reaction. J. clin. Path., 26, 224-234
Ayer, H.E. & Lynch, J .R. (1967) rbtes and fibrs in the air of asbestosprocessing plants and hygienic crìteria for airborne asbèstos.In: Davies, C. N., ed., Inhled Paricles and Vapours, II, OxfordPergarn, pp. 511-522
Badollet, M.S. (1948) Research on asbestos fibrs. Caad. Min. l'~tall.Trans., 51, 213-216
Badollet, M.S. (1952) Asbestos floats. Caad. Mi. ~tall. Trans., 55,185- 189
Badollet, B.S. & Edgerton, N.W. (1961) Th magnetic content of asbstosby magnetic senaation. Caad. Min. ~tall. BulL., 64, 56-59
Badollet, M.S. & C'::tt, W.A. (1965) Preparation of asbestos fibrs forexprÍ1ntal use. An. N.Y. Acad. Sci., 132, 451-455
Badollet, M.S. & Streib, w.c. (1955) Heat treatit of chrsotilefibrs. Canad. Mi. Metall. Trans., 58, 33-37
Baten, A.M. (1959) Economic Mieral DePOsits, 2nd ed., NEW "York, JohnWiley and Sons, pp. 94-106, 749-755
85
Bates, T.F. (1958) Selected Electron Hicrographs of Clays and oter Fine-Grained Minerals: Final Reprt on the Investigation of l'brohologand Structure of Fine-r,rained l'tierals, Circular 51, College Park,Pennsy 1 vania State Uni versi ty, College of l'lleral Industr
Bates, T.F. (1959) M)rpholog and crystal chemstry of 1:1 layer latticesilicates. Amr. Mineral., 44, 78-114
Bates, T.F., Sand, L..-r~. & Hink, J.F. (1950) Tuular crystals ofchrsotile asbestos. Science, 111, 512-513
Bek, E.G. & Bruch, J. (1974) Effet des poussieres fibreuses sur lesmacrophages alvéolaires et sur d'autres cellules cul ti vées in vi tro.Etude biochique et Ilrphologique. Rev. franç. 1'£1. resp., 2,Suppl. l, 72-76
Beck, E.G., Bruch, J., Friedichs, K.-H., Hilscher, Td. & Pott, F. (1971)Fibrous silicates in animl expriInts and cell -culture. Morpho-logical cell and tissue reactions according ta different physicalchemcal influences. ln: Walton, W.H., ed., Inaled Paricles andVapours, III, VoL. l, Old i'lking, Surey, Unwin, PP. 477-486
Beck, E.G., Holt, P.F. & Maojlovic, N. (1972) Cæiison of effects onmacrophage cutures of glass fibre, glass pcer and chrsotileasbestos. Brit. J. industr. Me., 29, 280-286
Beckett, S.T. (1973) The evaluation of airborne asbestos fibres using ascaning electron microscope. An. occu. Hyg., 16, 405-408
Beckett, S.T. & Attfield, M.D. (1974) Inter-labratory coisons of theconnting of asbestos fibres sanled on rrrane filters. A-l. ocCUP.Hyg., 17, 85-96
Beintker, E. (1931) Die Asbestosis der Lungen. Arch. C':ierbepath.Geerbeyg., ~, 345-358
Berr, G., Newhouse, M.L. & Tuok, M. (1972) Ccined effect of asbestosexpsure and snkig on nortli ty from lnng cacer in factory workers.Lacet, ii, 476-479
Biava, P.M., Ferri, R., Spacal, B. & De (':iaro, R. (1976) Cancro dalavoro a Trieste: il rrsoteliom della pleura. Sapere, 793, 41-45
Bignon, J., Goni, J., Bonnaud, G., Jaurand, M.C., Duour, G. & Pinchon, H.C.(1970) Incidence of pulna ferruginous boies in ?rance.Environm. Res., 3, 430-442
Biles, B. & Elrson, T.R. (1968) Exnation of fibres ln ber.Nature (Land.), 219, 93-94
86
Bohlig, H. & Hain, E. (1973) Cacer in relation to enviroruntal eXPsure.ln: Boovski, P., Gilson, J. C., Timrell, V. & Wagner, LT. C., ed,Biological Effects of Asbestos, Lyon, International ACfency for R.searchon Cancer (IAC Scientific Pulications No. 8), po. 217-221
Bohlig, H., Dabbert, A.F., Dalquen, P., Hain, E. & Hinz, 1. (1970)
Epidemolog of malignt ræsotheliom in HaJurg. A orelimnarreport. Environm. Res., i, 365-372
Borow, M., Conston, A., Livornese, L. & Schalet, N. (1973)following expsure to asbestos: a review of 72 cases.641-646
MesotheliomChest, 64,
Boutin, C., Pietri, J.-F., Choux, R., Arud, A. & Serafino, X. (1976)La mine d' alante de Caari, enquête iricale prélimnaire.Marseille Mé., 110, 107-118
Brindley, G.W. & Zussm, J. (1957) A structural study of the thermltransformtion of serptine mierals ta forsteri te. Arr. Mineral.,42, 461-474
Burilkov, T. & Badjov, L. (1970) Ein Beitrag zum endemschen Auftretendoppelseitiger Pleuraverkalkungen. Prax. Pnuml., 24, 433-438
Burilkov, T. & Michailova, L. (1970) Asbestos content of the sail andendemc pleural asbestosis. Environm. Res., i, 443-451
Burilkov, T. & Michailova, L. (1972) übr den Sepiolitgehlt des Baensin Geieten mit endemschen Pleuraverkalkungen. Int. Arch. Arbeits-ned., 29, 95-101
Caplan, A., Gilson, J.C., Hinson, K.F.W., McVittie, J.C. & Wagner, J.C.(1965) Radiological and pathological correlations in asbestosisin the Republic of South Africa and the United Kigdom. II. Aprelimna study of observer variation in the classification ofradiOÇraphs of asbestos-expsed workers and the relation of pathologand X-ray appeances. An. N.Y. Acd. Sci., 132, 379-386
Clifton, R.A. (1972) Asbestos. In: 1972 Bueau of Mies H:inerals Yearbok,Washington OC, US Governt Printing Office
Clifton, R.A. (1974) Asstos. ln: 1974 :.ureau of Jvines ,r.ÜIerals Yearbok,Washington OC, US Governt Printing Office
Clifton, R.A., Jr, Huggins, C.W. & Shell, H.R. (1966) Hollow chrsotilefibrs. Arr. Mieral., 51, 508-511
Comrns, B.T. & Gibbs, G.W. (1969) Contaating organic material inasbestos. Brit. J. Cacer, 23, 358-362
"
87
Cok, P.M., Glass, G.E. & Tucker, J.H. (1974) Asbestifonn amhilellnerals: detection and ITasurert of high concentrations inmucipal water supplies. Science, 185, 853-855
Coke, W.E. (1927) Pulmna asbestosis. Brit. me. J., iv, 1024-1025
Coper, W. C., Black, R., P0J?dorf, W. & Gaffey, W. (1975)' Study ofSheet Metal WOrkers - Final Report, Contract HSM-099-7l-55,Washington OC, US Depatmt of Heal th, Education and Welfare,National Institute for Occupational Safety and Health
Cuingha, H.M. & Pontefract, R.D. (1971) Asbestos fibres in beveragesand drining water. Nature (lDnd.), 232, 332-333
Cuingham, H.M. & Pontefract, R.D. (1973) Asbestos fibres in beverages,drinng water and tissues: their passage though the intestinalwall and novert though the boy. J. Ass. off. anlyt. Chem., 56,976-981
Cuingha, H.M. & Pontefract, R.D. (1974) Placental tranfer of asbestos.Nature (lDnd.), 249, 177-178
Daa, E.S. & Ford, W.E. (1957) A Textbexk of Mieralog, 4th ed., New York,John Wiley and Sons, p. 674
Davis, J.M.G. & Gross, P. (1973) Are ferruginous boies an indication ofatnspheric pollution by asbestos? ln: Boovski, P., Gilson, J .C.,Timrell, V. & Wagner, J. C., eds, Biological Effects of Asbestos,Lyon, Interntional Agency for Research on Cacer (!AC ScientificPulications No. 8), pp. 238-242
Der, W.A., Howie, R.A. & Zussm, J. (1962) Rock-Formng l'inerals,VoL. 3, Sheet Silicates, Ne York, John Wiley and Sons, pp. 170-175,185- 187
Der, W.A., Howie, R.A. & Zussm, J. (1967) Rock-Formg Mierals,VoL. 2, Chain Silicates, LDndon, lDngms, pp. 203-210
De Lajartre, N., De Lajare, A.-Y., Michaud, J.-L., Reaux, A.,Dupon, H., Musini, J. & Cornet, E. (1973) Mésothéliors pleurauxdiffus (Etude prélimaire sur 31 cas oprés). Rev. franç. Mal.resp., l, 697-710
De Lajare, M., Cornet, E., Corroller, J., MJigneteau, C.R., Dun, H.,Reux, A., Michaud, J .-L., Chritte, A. & Gugelot, A. (1976)Etude clinique et professionnelle de 54 mésothéliors pleuraux diffus.Rev. franç. MaL. resp., i, Suppl. 2, 63-74
I:t, J .M., Zumalde, R.D. & Wallingford, K.M. (1976)asbestos fibr exsures in a had rock gold mie.Sci., 271, 345-352
Discussion paper:An. N.Y. Acad.
88
Diller, J. S. (1919) Asbestos, us Gelògical Surey. rtineral Resources,Par II, t\Tashigton OC, US Goernt Printing Office, p. 302ff
Dohner, V.A., Bele, R.G. & Miller, W.T. (1975) Asstos exsure andnnltiple prli turrs. Arr. Rev. resp. Dis., 112, 181-199
Doll, R. (1955) r-rtality fro lnng cacer in asbestos workers.Brit. J. industr. ~., 12, 81 -86
Doll, R. (1971) The age distribution of cacer: :llications for rrelsof carcinogenesis. J. roy. stat. So., 134,133-166
Doniach, L, Swetten, K.V. & Hathorn, M.K.S. (1975) Prevalence ofasbestos boies in a necropsy series in East wndon: assoiation wi thdisease, occupation and donciliar address. Bri t. J. industr. ~.,32, 16-30
Donn, A. (1970) Turi speriitali da amanto di crisotilo, crocidolitee amsite in ratto Sprague-Daley. ~. Lavoro, 61, 1-32
Dreessen, W.C., Dallavalle, J.M., Edds, T.I., t-'lller, J.W. & Sayers, R.R.(1938) A study of asbestosis in the asbestos teile industr.us Pul. Hlth Serv. BulL., 241, v.lashington OC, US Governt PrintingOffice --
Edge, J.R. (1976) Asbestos related disease in Barow-in-Fuess.Environm. Res., 11, 244-247
Elms, P.C. & Simson, M.J.C. (1971) Inulation workers in Belfast. III.r-rtality 1940-66. Brit. J. industr. ~., 28, 226-236
Enterline, P.E. (1965)the United States.
M:rtali ty anng asbestos products workers inAn. N.Y. Acad. Sei., 132, 156-165
Enterline, P.E. & Henderson, V. (1973)cancer in the asbestos industry.
Ty of asbestos and respiratoryArch. environm. Hlth, 27, 312-317
Enterline, P., De Coufle, P. & Henderson, V. (1972) l-rtlity inrelation to occutional exsure in the asbestos industr.J. occup. ~., 14, 897-903
Enterline, P., De Coufle, P. & Henderson, V. (1973) Respiratory cacerin relation to occupational expsures aTng retired asbestos workers.Brit. J. industr. ~., 30, 162-166
Erst, W.G. (1968) Arhiles: crstal chemstr, phase relations andoccurrence. ln: Engelhadt, von W., Ha, T., Foy, R., Winchester, J.Vl.& Wy lie, P. J ., eds, Mierals, Roks and lnorganc Materials, New York,Springer-Verlag, pp. 4-18, 19-32
89
Evans, J .C., Ev, R.J., Holrs, A., Houn, R.F., Jones, D.M., M:rgan, A.& Walsh, M. (1973) Studies on th deposition of inaled fibrousmaterial in the respiratory tract of the rat and its subseqentcleaance using radioactive tracer technques. 1. urcc crocidoli teasbestos. Environm. Res., 6, 180-201
Fagan, D.M., ed. (1976) Asbestos, VoL. 58, WillCM Grave, Pa, Stover Pul.Co., pp. 16-47
Faust, G.T. & Fahey, J.J. (1962) The Serptine-Grup Mierals, US Gelogical Surey, Prof. Pr. 384-A, Washington OC, US Governt PrintingOffice, p. 92
Fondime, A. & Desbordes, J. (1974) Asbestos boies and fibrs ln lnngtissues. Environm. Hlth Perspet., 2., 147-148
Fondie, A., Sestien, P., Bignon, J., M:ncheaux, G. & Debordes, J.(1977) Etude qutitative de l'emussiérage asbestosique du pournet de la plèvre chez des sujets diverseit exsés. n1: Progsof the Symsium on the Patholog of Asstos, Rouen, France, 1975(in press)
French, B.M. (1968) Progessive Contact ~tarphism of the Biwaik IronFo:rtion, ~sabi Rage, Miesota, BulL. NJ. 45, Minneapolis,Miesota Gelogical Surey
Friedichs, K.H., Hilscher, W. & Sethi, S. (1971) Staub und Geeb-nntersuchungen an Ratten nach intraperitonealer Injektion von Asbest.Int. Arch. Arbeitsi., 28, 341-354
Fulton, W.B., I:XxÜey, A., Matthews,. J .L. & Houtz, R.L. (1935) Asbestosis.Par II, The Nature and Arunt of Out Encountered in AsbestosFabricating Plants; Part III, Th Effects of Exsure to OutEncountered in Asbestos Fabricating Plants on the Health of a Groupof WJrkers, Spial Bulletin NJ. 42, Harrisburg, Pensylvana,DePabæt of Lar and Industry, Bueau of Industrial Stadards
Gaze, R. (1965) Th physical and nolecular strcture of asbestos.An. N.Y. Acad. Sei., 132, 23-30
Gibbs, G.W. (1975) Fibre release from asbestos garts. An. occu. Hyg.,18, 143-149
Gibbs, G.W. & Hwg, C.Y. (1975) Physical Paanters of airborne asbestosfibres in various work enviroruts - prelirnar findings.Arr. industr. Hyg. Ass. J., 36, 459-466
Gibl, W., lDhs, K., Horn, K.-H., Wildner, G.P. & Hoffm, F. (1976)Tierexrirtelle Untersuchungen tlr eine kazerogene Wirknng vonAsbestfiltermterial nach oraler Aufnal. Arch. Geschwstforsch.,46, 437-442
90
Gillam, J .D., Det, J .M., I., R.A., Wagoner, J .K., Archer, V.E. &Blejer, H.P. (1976) MJrtality patterns aTng had rock gold llnersexsed ta an asbestiform mineraI. An. N.Y. Acad. Sei., 271, 336-344
Gilson, J .C. (1971) Asstos health hazards. So imlications of newknowledge to prevention. ln: Proeeè.ings of the IVth InternationalPneumniosis Conference, Bucharest, 1971, Bucharest, ApÌTndia
Gilson, J .C. (1973) Asbestos cancer: past and future hazards. Proc.roy. So. ~~., 66, 395-403
Gloyne, S.R. (1935)in asbestosis.
Tv cases of squs cacinoma of the lnng occuringTurcle, 17, 5-10
Gobbato, F. & Ferri, R. (1973) Ricerca epidemologica sull 1 incidenza delIlsoteliom della pleura nella provincia di Trieste. Iav. uro, 25,161-171
Gcwin, M.C. & Jagatic, J. (1970) Asbestos and nesothelioms. Environm.Res., l, 391-416
Greenbrg, M. & Lloyd Davies, T.A. (1974) ~sotheliom register 1967-68.Brit. J. industr. ~., 31, 91-104
Gross, P., deTreville, R.T.P., 'Ilker, E.B., Kachak, M. & Bayak, M.A.(1967) Exriital asbestosis: Th developt of lnng cacer inrats with pulrnar deposits of chrsotile asbéstos dust. Arch.environm. Hlth, 15, 343-355
Gross, P., Haley, R.A., Swure, L.M., Davis, J.M.G. & Greee, W.B. (1974)Ingested mieral fibrs. DJ thy peetrate tissue or cause cacer?Arch. environm. Hlth, 29, 341-347
Raon, N. & Eckert, H.L. (1976) Depression of viral interferon inuctionin cell monolayers by asbestos fibrs. Environm. Res., 11, 52-65
Hain, E., Dalquen, P., Bohlig, H., Dabert, A. & Hiz, 1. (1974) Kata-nestische Untersuchungen zur Ceese des ~sotheliom. Bericht ßbr150 Fälle aus dem Haurger Raum. Int. Arch. Arbeits., 33, 15-37
Hand, E.C. & Selikoff, I.J. (1973) Relation of cigarette smking torisk of death of asbestos-assoiated disease aTng inulation vvrkersin the United States. ln: Boovski, P., Gilson, J. C., Timre 11 , V.& Wagner, J.C., eds, Biological Effects of Asbestos, Lyon, InternationalAgenC'J for Research on Cacer (!AC Seientific Pulications NJ. 8),pp. 312-317
Hannd, E.C., Selikoff, 1.J. & Churg, J. (1965) Neoplasia aTng insulationworkers in the United States with spial reference to intra-abornalneoplasia. An. N.Y. Acad. Sei., 132, 519-525
91
Hargreaves, A. & Taylor, W.H. (1946) An X-ray exation of decmpsitionproducts of chrsotile (asbestos) and serptine. Mieral. Mag., 27,204-216
Haington, J. S. (1962) Occuence of oils containing 3: 4-bezpyrene andrelated substaces in asbestos. Nature (IDnd.), 193, 43-45
Haington, J.S. (1965) Chemcal studies of asbestos. Ar. N.Y. Acad. Sei.,132, 31-47
Harington, J.S. & Roe, F.J.C. (1965)fibrs and their natural ails.
Studies of cacinogenesis of asbestosAr. N. Y. Acad. Sei., 132, 439-450
Haington, J. S., Gilson, J .C. & Wagner, J .C. (1971) Asbestos and neso-thelioma in ma. Nature (Lond.), 232, 54-55
Harries, P.G. (1968) Asbestos hazards in naval dockyards. Ar. occu. Hyg.,11, 135-145
Haries, P.G. (1976) Exrience with asbestos disease and its control inGreat Britain's naval dockyards. Environm. Res., 11, 261-267
Ha, C.F. & Blaszak, T.P. (1974) Chacterization and Control ofAsbestos Emssions froID Op Sources, EPA oontract 68-02-1348,Washington OC, National Tehnical Inormtion Seice, us DePantof Corce
Hendr, N. W. (1965) The geolog, occurences and major uses of asbestos.Ar. N.Y. Acad. Sei., 132, 12-22
Hess, H.H. (1955) Serpntines, arogeny and epirogeny. In: Poldervaar, A.,ed., Crut of the Eath, Ne York, Gelogical Soiety of AIrica,pp. 391 -408
Hoffm, F .L. (1918) l-rtality from respiratory diseases in dusty trades(inorganic dust). BuL. US Bu. Lar Stat., 231, 176-180
Holms, A. & M:rgan, A. (1967) Lechig of constituents of chsotileasbestos in vivo. Nature (Lond.)., 21:i, 441-442
Holt, P.F. & Yonng, D.K. (1973) Asbestos fibres in the air of to.s.Atmsph. Environm., 7, 481-483
Holt, P.F., Mills, J. & Young, D.K. (1965) Exriital asbestosis withfour typs of fibrs: imrtce of smll paicles. Ar. N. Y.Acad. Sei., 132, 87-97
Hueper, W. C. (1965) Occupational and nonoccupational exsures to asbestos.Ar. N. Y. Acad. Sci., 132, 184-195
Huggins, C.W. & Shell, H.R. (1965) Deity of bulk chrsotile and massiveserptine. Amr. Mieral., 50, 1058-1067
92
IA (1972) Anual Report, 1971, Lyon, International Agency for Researchon Cacer, p. 46
IA (1973) IA M::mogaphs on the Evluation of Cacinogenc Risk ofChemcals to Ma, 2, So inorganic and organonetallic CDunds,Lyon, International Agency for Research on Cacer, pp. 17-47
Infante, P.F. & Le, R.A. (1976) Asstos in dentistr. J. Air. dent.Ass., 93, 221-222
Jagodzinski, H. & Kunze, G. (1954a) Die Rollchenstrtur des Chsotils.1. Allge.ine Beu9tgstheorie und Kleinwindelstreug. NeuesJahbuch fUr Mieralogie, !, 95-108
Jagodzinski, H. & Kunze, G. (1954b)II. wei twinkelinterferenzen.113-130
Die Rollchenstrtur des Chsotils.Neues Jahbuch fUr Mieralogie, ~,
Jaurand, M.C., Sestien, P., Bignon, J., Jeaot, P., Rem:md, G. &Goni, J. (1975) Application de la microscopie électronique à l'étudedes paicules inalées. J. Microsc. Biol. cell., 22, 463-464
Jaurand, M.C., Goni, J., Jeanot, P., Sestien, P. & Bignon, J. (1976)Solubilité du chsotile in vitro et das le poUTn humin.Rev. franç. Mal. resp., !, Suppl. 2, 111-120
Johansen, A. (1937) A Descriptive Petrogaphy of the Igneous Roks,Vol. 3, The Intenæiate Roks, Vol. 4, The Foldspathoid Rocks, ThePeriodotites and Perknites, Chcago, University of Chcago Press,pp. 360, 511
Jones, J. S. P., Pooley, F .D. & Snth, P .G. (1976) Factory populationsexsed to crocidoli te asbestos - a continuing surey. In :Rosenfeld, C. & Davis, W., eds, Environnntal Pollution andCacinogenic Risks, Lyon, International Agency for Research onCacer (IA Scientific Pulications No. 13), pp. 117-120
Kalousec, G.L. & Muttar, L.E. (1957) Studies on the chrsotile andantigorite compnents of serptine. Air. Mieral., 42, 1-22
Kaachaova, V.N., Olshvang, R.A. & Kogan, F.M. (1969) On changes ofcertain organs after intraperitoneal adnistration of asbestoscontaining dust in exrimt. Byl. eksp. BioL. ~., 67, 117-120
Keean, R.G. & Lynch, J .R. (1970) Techniques for the detection, identifi-cation and anl ysis of fibrs. Arr. industr. Hyg. Ass. J., 31,587-597
Kiviluoto, R. (1960) Pleural calcification as a roetgenologic sign ofnon-oc~pational enemc anthophyllite-asbestosis. Acta radiol.,Supl. 194, 1-67
93
Kleinfeld, M., ~ssite, J., Koym, O. & Zaki, M.H. (1967) MJrtity aingtalc llers an millers in Ne York state. Arch. envirorn. Hlth,14, 663-667
Kleinfeld, M., læssite, J. & Lager, A.M. (1973) A study of workersexpse to asbestifonn llerals in corcial talc maufacture.Envirorn. Res., 6, 132-143
Kleinfeld, M., ~ssite, J. & Zaki, M.H. (1974) MJrtlity exiences aingtalc workers: a follow-up study. J. occu. ~., 16, 345-349
Knox, J.F., Holns, S., 1)11, R. & Hill, 1.D. (1968) rbrtlity from lungcancer and other causes aing workers in an asbestos texile factory.Brit. J. industr. læ., 25, 293-303
Kogan, F.M., Guselnikova, N.A. & Guevskaya, M.R. (1972) Th cacernortlity rate aing workers of asbestos industr of the Urals.Gig. i Sait., 37, 29-32
Lager, A.M. & Poley, F.D. (1973) Idetification of single asbestos fibresin hum tissues. In: Boovski, P., Gilson, J. C., Timrell, V. &Wagner, J .C., eds, Biological Effects of Asstos, Lyon, InterationalAgency for Reseach on Cacer (lA Scientific Pulications N:. 8),pp. 119-125
Lager, A.M., Selikoff, 1.J. & Satre, A. (1971) Chsotile asbestos inthe lnngs of Pesans in Ne York City. Arch. envirorn. Hlth, 22,348-361
Lager, A.M., Ruin, 1. B. & Selikoff, 1.J. (1972a) Chcal chacteizationof asbestos boy cores by electron microprobe anal ysis. J. Histochem.
Cyhem., 20, 723-734
Lager, A.M., Rubin, 1.B., Sel ikoff, LJ. & Pooley, F.D. (1972b) Chemcalchaacterization of nncoated asbestos fibrs fra the lungs of asbestosworkers by electron microprobe anl ysis. J. Histochem. eyhem., 20,735-740
Lager, A. M., Mackler, A. D. & Pooley, F. D. (1974) Electron microscicalinvestigation of asbestos fibrs. Envirorn. Hlth Pespe., ~, 63-80
Lager, A.M., WJlff, M.S., Rohl, A.N. & Selikoff, 1.J. (1977) variationofsor physical," checal and biological propeies of chrsotile asbestossubjected to prolonged milling. J. 'Ixicol. envirorn. Hlth (in press)
Le Bouffant, L., Main, J.C., Bruère, S., Tichoux, G. & Normd, C.(1977) Quelques observtions sur les fibres d'amante et lesfonntions llnérales rencontrées das les pourns asbestosiques.ln: Proceeings of the Sysium on the Patholog of Asbestos,Rouen, France, 1975 (in press)
94
Leicher, F. (1954) Pri1er Dekzellenturr des Bauchfells bei Asstose.Arch. Geerbepath. Gerbeyg., 13, 382-392
Levy, B.S., Sigudson, E., M:del, J., Laudon, E. & Peason, J.Investigating possible effects of asbestos in city water:of gastrointestinl cacer incidence in Duuth, Miesota.Amr. J. Epidemol., 103, 362-368
Liebling, R.S. & Lager, A.M. (1972) Optical proies of fibrous brucitefrom Asbestos, Quc. Air. Mieral., 57, 857-864
(1976)sureillace
Lorirr, W. V., Rohl, A. N., Miller, A., Nicholson, i-v. J. & Selikoff, 1. J .(1976) Asbestos exsure of brake repair workers in th united States.Mt Sini J. ~., 43, 207-218
Lynch, K.M. & Smth, W.A. (1935) Puna asbestosis. III. Cacinamof lung in asbestos-silicosis. Air. J. Cace, 24, 56-64
Lynch, K.M., Mclver, F .A. & Ca, J .R. (1957) Puna turrs in miceexse ta asbestos dust. Arch. industr. Hlth, 15, 207-214
.Mltoni, c. & Anoscia, c. (1974) ~otheliom in rats follCMing theintraperitoneal injection of crocidolite. In: Davis, W. &.M 1 toni, C., eds, Advaces in Tuur Prevention, Detection andChacterization, Vol. l, Chacterization of Hum Tuurs,Amterda, Excerpta ~ica, pp. 115-116
.Mcuo, T.F. & Coulter, E.J. (1963) ~thodolog in industrial healthstudies. The cohort approach, wi th spial reference to an asbestoscompany. Arch. envirori. Hlth, ~, 210-226
Macuo, T.F. & El-Atta, A.A. (1967) M:rtlity patte in a cohort ofasbestos workers. A study base on emloyt exrience.J. occu. ~., 2-, 147-162
Matischnig, K.M., Neell, D.J., Basley, W.C., CC, W.K., Fein, E.L.& Oliver, E. (1977) Unsuspeted exsure to asbestos and bronchogenccarcinom. Brit. ne. J. (in press)
.Mser, M., Rice, R.V. & Klug, H.P. (1960) Chsotile norpholog.Amr. Mieral., 45, 680-688
.Mson, B. (1958) Principles of Geemstr, 2nd ed., Ne York, JohnWiley and Sons, pp. 111-113
.Msson, T.J., McKay, F.W. & Miller, R.W. (1974) Asstos-like fibs inDuuth water supply. Relation to cancer nortlity. J. Ar. ne.Ass., 228, 1019-1020
95
M:y, T.C. (1965) Appdix 3: Statistical tales - asbestos. An. N.Y.Acad. Sci., 132, 745-765
NcDonald, A.D. & McDonald, J .C. (1976) Etudes épidérologiqus sur lesmaladies dues à l'amante au Caada. Rev. franç. M:l. resp., !,Suppl. 2, 25-38
McDonald, A.D., M:gner, D. & Eyssen, G. (1973) Prim malignt neso-thelial tUIrs in Cada, 1960- 1968. A pathologic review by themesothelian Pael of the Caadian Tur Reference Centre. Cacer,31, 869-876
McDonald, J.C., Beklake, M.R., Gibbs, G.W., McDonald, A.D. & Rossiter, C.E.(1974) The health of chrsotile asbestos mine and mill workers ofQuebc. Arch. environm. Hlth, 28, 61-68
McDonald, S. (1927) Histolog of pulnnar asbestosis. Brit. ne. J.,ii, 1025-1026
McNulty, J .C. (1962) Malignt pleural nesotheliom in an asbestos worker.Me. J. Austr., 49, 953-954
~rewether, E.R.A. (1947) Anual Rert of the Chef Inpector of Factoriesfor the Year 1947, wndon, HMO, pp. 15-17
Merewether, E.R.A. & Price, C.W. (1930) Report of the Effecs of AsbestosOUt on the Lnngs and OUt Suppression in the Asbestos rndustr,wndon, HMO
~rliss, R.R. (1971) Talc and asbestos contaant of rice. J. .Ar.me. Ass., 216, 2144
~ur, L. (1966) Asbestos boies and pleural plaques in a Finshseries of autopsy cases. Acta path. TIcrobioL. scad., Suppl. 181,1-107
~ur, L.O., Honna, M., lSO, M. & Sutinen, S. (1970) Asbestosboies in the lungs of a series of Finish lung cacer patients.ln: Shpiro, H.A., ed., Pneumniosis. Proceegs of the Inter-national Conference, Johanesburg, 1969, Cape Tc, OXord UniversityPress, pp. 404-407
~ur, L.O., Kiviluoto, R. & Haam, M. (1974) rbrtlity and norbiditya.ng the working poulation of anthophyllite asstos miers inFinland. Brit. J. industr. M:., 31, 105-112
Miller, L., Smth, W.E. & Beliner, S.W. (1965) Tests for effect ofasbestos on bezo(a)pyene cacinogenesis in the respiratory tract.An. N.Y. Acad. Sci., 132, 489-500
96
Mills, R.G. (1930) Punar asbestosis: report of a case. Miesota~., 130, 495-499
Milne, J .E.H. (1976) Thrty-tw cases of nesotheliom in Victoria,Australia: a retrospeti ve surey related to occutional asbestosexpsue. Brit. J. industr. ~., 33,115-122
rbrgan, A. & Holms, A. (1970) Neutron activation techniques in investi-gations of the comsition and biological effects of asbestos.ln: Shapiro, H.A., ed., Pneumniosis. Proceedings of theInternational Conference, Johanesburg, 1969, Cape To, OxordUniversity Press, pp. 52-56
rbrgan, A., Holms, A. & Gold, C. (1971) Studies of the solubility ofconstituents of chrsotile asbestos in vivo using radioactive tracertechniques. Environr. Res., 4, 558-570
rbrgan, A., Evans, J.C., Evans, R.J., Honnam, R.F., Holms, A. & DJyle, S.G.(1975) Studies on the deposition of inaled fibrous material in therespiratory tract of the rat and its subseqent clearance using radio-active tracer techniques. Environm. Res., 10, 196-207
Morgan, R.W. & Shettigara, P.T. (1976)srking and largeal carcinoma.
Occupational asbestos exsure,An. N. Y. Acad. Sei., 271, 308-310
Muay, H.M. (1907) ln: Report of the Departal Cottee onCompsation for Industrial Disease, Hinutes of Evidence, Appendicesand Index, c.d. 3495-c.d. 3496, London, wy and Sons
Nagy, B. & Bates, T.F. (1952) Staility of chrsotile asbestos.Amr. Mineral., 37, 1055-1058
Nagy, B. & Faust, G.T. (1956) SerPtines: natural mixtures of chrsotileand antigorite. Amr. Mieral., 41, 817-838
Newhouse, M.L. (1969) A study of the nortlity of workers ln an asbestosfactory. Brit. J. industr. ~., 26, 294-301
Newuse, M.L. (1973a) Asbestos in the work place and the corrity.An. occup. Hyg., 16, 97-107
Newhuse, M.L. (1973b) Cacer am:mg workers in the asbestos teile industr.ln: Boovski, P., Gilson, J. C., Tllrell, V. & Wagner, J. C., ed,Biological Effects of Asbestos, Lyon, International Agency for Researchon Cacer (IAC Scientific Pulications No. 8), pp. 203-208
Newhouse, M.L. & Berry, G. (1973) Asbestos and largeal cacinoma.Lacet, ii, 615
Newhous, M.L. & Bery, G. (1976) Predctions of nortlity from neothelialtururs in asbestos factory ~rkers. Brit. J. industr. ~., 33,147-151
97
Newouse, M.L. & Thmpson, H. (1965) Mesotheliom of pleura and peritoneumfollCMing exsue to asbestos in the wndon area. Bri t. J. industr.~., 22, 261-269
Neous, M.L., Berry, G., Wagner, J.C. & Tuok, M.E. (1972) A study ofthe nortali ty of femle asbestos workers. Bri t. J. industr. Me., 29,134- 141
Ne, J. A., Archer, V. E., Saccomo, G., Kuschner, M., Auerbach, O.,Gronda, R.D. & Wilson, J.C: (1976) Histologic tys of bronchogeniccarcinom amng rrs of coPPe-mining and SI 1 ting cci ties.An. N.Y. Acad. Sci., 271, 260-268. -
Nicholson, W.J. & Pnndsack, F.L. (1973) Asstos in the environnt.ln: Boovski, P., Gilson, J. C., Tirrell, V. & Wagner, J. C., ed ,Biological Effects of Asbestos, Lyon, Intemational Agency forResearch on Cacer (IAC Scientific Pulications lb. 8), pp. 126-130
Nicholson, W.J., Maggiore, C.J. & Selikoff, 1.J. (1972) Asbestos conta-nation of paenteral drgs. Science, 177, 171-173
Nicholson, W.J., Rohl, A.N. & weism, 1. (1975) Asstos Contationof the Air in Pulic Buldings, EPA Contract lb. 68-02-1346,Washigtn OC, US Governt Printing Office
Nicholson, W.J., Rohl, A.N. & Weism, 1. (1976) Asstos Contaationof Bulding Air Supply System, Anls No. 75 CH 1004-1 29-6, Ne York,Insti tute of Electrical and Electronics Engineers, Inc.
Nicholson, W.J., Selikoff, 1.J., Harnd, E.C. & Seidm, H. (1977)l-rtlity exrience of asbestos factory workers: effect of differingintensi ties of asbestos exsure. Environr. Re. (in press)
NIOSH (National Institute for Occutiona Safety and Health) (1977)Re-Extion and Upate of Inormtion on the Health Effectsof Occupational Exsure to Asstos, Washington CC, US Departof Health, Education and Welfare (in press)
lbrdm, M. (1938) Der Berufskrebs der Asbestarbeiter. z. Krebsforsch.,47, 288-302
lbrdm, M. & SOrge, A. (1941) Lnngenebs durch Asbeststaub im Tierversuch.Z. Krebsforsch., 51, 168-182
Nuen, M. (1975) The epidemologic relationship betwee pleural neso-thelioma an asbestos exsure. Scad. J. WJrk Environr. Hlth, l,128-137
O:cella, E. & Maddalon, G. (1963) X-ray diffraction chracteristics ofsaT typ of asbestos in relation to differènt tehnques ofcaution. M3. Lavoro, 54, 628-636
98
Oldh, P.D. (1973) A trial of techniques for cormting asbetos boesin tissue. ln: Boovski, P., Gilson, J. C., Tirrell, V. &Wagner, J.C., eds, Biological Effec of Asstos, Lyon, InterationalAgency for Reseach on Cacer (IA Scientific Pulications No. 8),pp. 45-49
Pancost, H.K., Miller, T.G. & Ladis, H.R.M. (1917) A roentgenologicstudy of the effects of dust inalation upn the lungs. Tran .Ass. AIr. Phys., 32, 97-106
Peta, J., Howard, S., Kilen, L.J., 0011, R. & Leinohn, H.C. (1977)A nortality study aIng workers in an English asbestos factory.Brit. J. industr. ~. (in press)
Polderaar, A. (1955) Chstr of the ea 's crut. In: Polderv, A.,ed., Crut of the Ea, Ne York, eelogical Soiety of .Arica,pp. 119-144
Pooley, F .D. (1972) Electrn microscope characteristics of inaledchrsotile asbestos fibre. Brit. J. industr. ~., 29, 146-153
Poley, F .D. (1973) .Motheliom in relation ta exsure. ln: Boovski, P.,Gilson, J. C., Tirrell, V. & Wagner! J. C., ed , BiolOÇical Effects ofAsbestos, Lyon, International Agency for Reearch on Cacer (IAScientific Pulications No. 8), pp. 222-225
Poley, F.D. (1975) Th identification of asbestos dust with an eleconmicroscope llcroprobe analyser. An. occu. Hyg., 18, 181-186
Pooley, F .D. (1976) An extion of the fibrous lleral content ofasbestos lnng tissue from the Caadian chrsotile ming industr.Environr. Res., 12 (in press)
Poley, F .D. & Rolands, N. (1977) Chcal and physica propertes ofBritish talc poers. ln: Walton, W.C., ed., Inaled Pariclesand Vapours, IV, Ne York, PergaIn (in press)
Pooley, F.D., Oldh, P.D., Ur, C.-H. & Wagner, J.C. (1970) The detectionof asbestos in tissues. ln: Shpiro, H.A., ed., Pneumniosis.Proceegs of the Interntional Conference, Johanesburg, 1969,Cape Tow, Oxord University Press, pp. 108-116
Pott, F. & Friedichs, K.H. (1972) Turen der Ratte nach i.p.-Injektionfaserförmger Stäub. Naturissenchften, 59, 318
Pott, F., Huth, F. & Friedichs, K.H. (1972) Turen der Ratte nach Lp.Injektion von gerlenem Chsotil und Bezo (a)pyen. Zbl. Bat.Hyg., L Abt. Orig. B, 155, 463-469
99
Pott, F., Friedichs, K.-H. & Huth, F. (1976) Ergebisse aus Tierversuchenzur kazerOÇenen Wirkung faserförmger Stäub nnd ihe Deutung imHinlick auf die Turentstehung beir ~chen. Zbl. Bat. Hyg.,L Abt. Orig. B, 162, 467-505
Prasad, N.A. & Poley, F.D. (1973) Chacteristics of amhile asbestosdust surfaces in aqueous rria. J. appL. Chem. BiotechnoL., 23,675-687
Pudsack, F .L. (1956) The properties of asbestos. II. The density andstrcture of chrsotile. J. phys. Chem., 60, 361-364
Pudsack, F .L. (1961) The pore strcture of chrsotile asbestos.J. phys. Chem., 65, 30- 33
Pudsack, F. & Reirchussel, G. (1956) The proprties of asbestos. III.Basicity of chrsotile sussions. J. phys. Chem., 60, 1218-1222
Putoni, R., Valerio, F. & Santi, L. (1976) Il nesoteliom pleurico frai lavoratari del porto di Geova. Turi, 62, 205-210
Pylev, L.N. (1972) Morphological lesions in rats lungs, induced by intra-tracheal injection of chrsotile-asbestos alone and with bez (a)-
pyrene. Vop. OnoL., 18, 40-45
Pylev, L.N. & Shabd, L.M. (1973) Sa results of exrinta studiesin asbestos carcinogenesis. ln: Boovski, P., Gilson, J. C. ,Timrell, V. & Wagner, J. C., ed , Biological Effects of Asbestos,Lyon, International Agency for Research on Cacer (lA ScientificPulications No. 8), pp. 99-105
Reeves, A.L. (1976) The carcinogenic effect of inaled asbestos fibrs.An. clin. La. Sci., 6, 459-466
Reeves, A.L., Puo, H.E., Smth, R.G. & Vorwld, A.J. (1971) Exrintalasbestos carcinogenesis. Environr. Res., !, 496-511
Reeves, A.L., Puo, H.E. & Smth, R.G. (1974) Inlation cacinogenesisfram various forr of asbestos. Environr. Re., ~, 178-202
Rickards, A.L. (1973) Estimtion of subcrogam qutities of chrsotileasbestos by electron microscopy. Anlyt. Chem., 45, 809-811
Ro, F.J .C., Walters, M.A. & Harington, J .S. (1966) Tuur intiation bynatural and contamating asbestos oils. Int. J. Cacer, l, 491-495
Rohl, A.N. & Lager, A.M. (1974) Identification and quantitation ofasbestos in talc. Environr. Hlth Perspet., ~, 95-109
Rohl, A.N., Lager, A.M., Selikoff, I.J. & Nicholson, W.J. (1975) Exsureta asbestos in the us of consUlr spckling, patchig and tapingcomunds. Science, 189, 551-553
100
Rohl, A.N., Lager, A.M., WJlff, M.S. & Weism, 1. (1976)exsure during brake lining maintence and repir.12, 110-128
AsbestosEnvironm. Res.,
Rohl, A.N., Lager, A.M., Klintidis, R., WOlff, M.S. & Selikoff, 1.J.(1977) Asbestos content of dust encountered in brake maintence andrepair . Pro. roy. So . M:., 70 (in press)
Rosato, D.V. (1959) Asstos - Its Industrial Aplications, Ne York,Reinhold
Ruino, G.F., Scaetti, G., Ibnna, A. & Palestro, G. (1972) Epidemologof pleural rrsothelioma in nort-western ltaly (Piednt). Brit. J.industr. ~., 29, 436-442
Salk, R. & Vosare, A. (1975) Induction of lung tUIrs in rats byintratrachea1 instillation of bezo (a)pyene and chrsotile asbestosdust. ln: Exrintal and Clinical OnexÜog, Vol. 2, Tallin,Valgu, pp. 88-94
Schelz, J .P. (1974) The detection of chrsotile asbestos at lCM levels intalc by differential thernl anlysis. Themo. acta, ~, 197-204
Schneiderr, M.A. (1974) Digestive syste cacer aTng persons subjectto occupational inlation of asbestos Paicles: a li terature reviewwith emhasis on dose response. Environm. Hlth Persp., 2., 307-311
Schreibr, G. (1974) Ingeste dyed cellulose in the blcx and urine of ma.Arch. environm. Hlth, 29, 39-42
Sebstien, P. & Bignon, J. (1974) Contribution à l'Etude de la PollutionPariculaire de l'Ai Amiant de la Ville de Paris pa les Microfibrillesd'Amante, Rapprt Final, Contrat l'. 206, Paris, Miistère de laQulité de la Vie
Sestien, P., Bignon, J., Gaudichet, A., Duour, G. & Bonnaud, G. (1976a)Les pollutions atmsphériques urbaines pa l' asbeste. Rev. franç. MaL.resp., l, Suppl. 2, 51-62
Setien, P., Bignn, J., Fondime, A., Bientz, M. & Bonnaud, G. (1976b)M§trologie des fibres d' alante (asbeste) da le lXUIn humin.Contribution à l'évaluation du risqe asbestosique pour la poulationgénérale. Résuitats prélimires. ln: IIèr Sysium sur laReherche en Matière de Pollution AtIsphérique, Le Arcs, France, 1976,Paris, Miistère de la Qulité de la Vie.' Affaires Scientifiques
Sestien, P., Fondime, A., Bignon, J., rbnchaux, G., Desbordes, J. &Bonnaud, G. (1977) Toaphic distribution of asbstos fibres inhUI lung in relation with occutional and non-occutional exsure.ln: Walton, W.C., ed., Ined Paricles an ValXurs, IV, Ne York,PergaTn (in press)
101
Seidm, H., Lilis, R. & Selikoff, I.J. (1977) Short-tenu asbestos exsureand delayed cacer risk. In: Preeings of Thrd InternationalSysium on the Detection and Prevention of Cacer, Ne York, 1976(in press)
Selikoff, I.J. (1974) Epidemolog of gastrointestinal cacer. Environr.Hlth Perspt., ~, 299-305
Selikoff, I.J. (1976a) Lnng cacer and nesotheliom during prospetivesureillance of 1249 asbestos inulation workers, 1963-1974.An. N. Y. Acad. Sei., 271, 448-456
Selikoff, I.J. (1976b) Asstos disease in the Unted States, 1918-1975.Rev. franç. MaL. resp., !' Suppl. l, 7-24
Selikoff, I.J., Churg, J. & Harnd, E.C. (1964) Asstos exsure andneolasia. J. Amr. me. Ass., 188, 22-26
Selikoff, I.J., Churg, J. & Harnd, E.C. (1965) Relation betwexsure ta asbestos and nesotheliom. N' Engl. J. ~., 272, 560-565
Selikoff, I.J., Hand, E.C. & Churg, J. (1968) Asstos exsure, srkigand neolasia. J. Amr. ne. Ass., 204, 106-112
Selikoff, I.J., Hand, E.C. & Churg, J. (1970) rbrtlity exriences ofasbestos insulation workers, 1943-1968. ln: Shpiro, H.A., ed.,Pneurniosis. Proceegs of the International Conference,Johanesburg, 1969, Cape 'l, Oxord University Press, pp. 180-186
Selikoff, I.J., Nicholson, W.J. & Lager, A.M. (1972a) Asstos airpollution. Arch. environr. Hlth, 25, 1-13
Selikoff, I.J., Harnd, E.C. & Churg, J. (1972b) Cacinogenicity ofaisite asbestos. Arch. environr. Hlth, 25, 183-186
Selikoff, I.J., Ha:nd, E.C. & Seidm, H. (1973) Cace risk of inulationworkers in the united States. ln: Boovski, P., Gilson, J. C. ,Timrell, V. & Wagner, J. C., ed , Biological Effects of Asstos, Lyon,Intetional Agency for Reearch on Cacer (IAC Scientific Pulica-tions No. 8), pp. 209-216
Seior Mecal Inspetor 1 s Adisory Panel (1968) Problem Arising From theUse of Asstos, lDndon, HMO
Shabd, L.M., Pylev, L.N., Krivosheeva, L.V., Kulagin, T.F. & Neo, B.A.(1974) Exriital studies on asbestos cacinogencity. J. nat.Cacer Inst., 52, 1175-1187
Shettigara, P.T. & M:rgan, R.W. (1975) Asbestos, srking and largealcacinan. Arch. environr. Hlth, 30, 517-519
102
Sincok, A.M. (1977)materials. ln:(in press)
In vitro chorsomal effects of asbestos and otherOrigins ot Hur Cacer, Cold Spring Harbour, 1976
Sincock, A. & Searight, M. (1975) Induction of chronoS0 chges inChinese hamter cells by exsure ta asbestos fibrs. Nature (lDnd.),257, 56-58
Skidnre, J. W. & Jones, J. S. P . (1975) rbnitoring an asbestos sprayprocess. Ar. occup. Hyg., 18, 151-156
Smth, W.E. & Hubrt, D.D. (1974) Th intrapleural route as a neans forestimting carcinogenici ty . ln: Kabe, E. & Park, J. F ., ed ,Exrimtal Lnng Cacer, Belin, Springer-Verlag, pp. 92-101
Smth, W.E., Miller, L. & Churg, J. (1970) An exriital rrel for studyof coccinogenesis in the respiratory tract. ln: Nettesheim, P.,Haa, M.G., Jr & Detherage, J .W., Jr, eds, M:rpholog of ExrimtalRespiratory Cacinogenesis, Oa Ridge, US Atorc Energy Cossion,pp. 299-316
Speil, S. & Leinewr, J.P. (1969) Asbestos minerals in rrern technlog.Environr. Res., 2, 166-208
Staton, M.F. (1973) So etiological considerations of fibre cacino-genesis . ln: Boovski , P., Gilson, J. C., Timrell, V. & Wagner, J. C. ,eds, Biological Effects of Asstos, Lyon, International Agency forReseach on Cacer (IAC Seientific Pulications J:. 8), pp. 289-294
Stanton, M.F. & Wrench, C. (1972)asbestos and fibrous glass.
~hanism of nesotheliom induction wi thJ. nat. Cacer Int., 48, 797-821
Stell, P.M. & Mcill, T. (1973) Asstos and largeal cacinom. Lacet,ii, 416-417
Sturhius, J. (1971) Epidemolog of nesoteliom on Walcheren Island.Brit. J. industr. ~., 28, 59-66
Stur, W. & Bittersohl, G. (1975) Beicht Übr die 2. ~otheli~Konferenzvor 3. bis 5. Mai 1974 in Wien. z. ges. Hyg., 21, 254-257
Thomson, J.G. & Graves, W.M., Jr (1966) Asstos as an urba air conta-nant. Arch. Path., 81, 458-464
Timrell, V. (1965) The inalation of fibrous dusts. Ar. N.Y. Acad. Sei.,132, 255-273
Timrell, V. (1972) Inhalation and biological effects of asbestos. In:~rcer, T. T ., M:rrCM, P. E ~ & StÖbr, W., ed, Assessrt of AirborneParicles. Fuartals, Aplications and :rlication to InalationToxicity, Springfield, IlL., Thmas, p. 429
103
Tirrell, V. (1975) Aligrnt of respirable asbestos fibres by magneticfields. An. accup-. Hyg., 18, 299-311
Tirrell, V. & Redall, R.E.G. (1971/72) Prepaation of the urcc stadardreference samles of asbestos. Power Technol., 5, 279-287
Tirrell, V., Pooley, F.D. & Wagner, J.C. (1970) Chacteristics ofrespirable asbestos fibres. ln: Shaoiro, H.A., ed., Pneurniosis.Proceeings of the International Conference, Johanesburg, 1969,Cape To, Oxford University Press, pp. 65-70
UICC (International Union against Cacer) (1965)of the Working Group on asbestos and cancer.132, 706-721
Report and reconmdationsAn. N. Y. Acad. Sei.,
US Bueau of Mines (1975) Mierals in the US Ecnom: Ten-year Suply-Ded Profiles for Mieral and Ful Ccities, i:~¡ashington OC,US Depant of the Interior, p. 10
US Depat of Health, Education and hTelfare (1972a) NIOSH-By (':ish.Heal th Services Wor ld, Rokville, M:
US Depa.nt of Health, Education and Welfare (1972b) OccuoationalExsure ta Asbestos, HSM 72-10267, Washington OC, National Institutefor Occupational Safety and Heal th
US Depart of Lar (1975) Occupational exsure ta asbestos.Federal Reister, 40, 47652-47665
US Envirorutal Protection Agency (1975) National emssion stadads forhazardous air r;llutants. Federal Reister, 40, 48291-48298
US Foo & Drug Adnistration (1976) Curent goo maufacturing practicefor finished ohaceuticals. Federal Register, 41, 16933
VolkheÌIr, G. (1973) Persorotion. Acta hepato-gastroeterol., 20, 361-362
VolkeÌIr, G. (1974)intestinal tract.
Passage of paicles though the wall of the gastro-Environm. Hlth Perspet., ~, 215-225
Voi:ld, A.J., Dukan, T.M. & Pratt, P.C. (1951) Exriital studies ofasbestosis. Arch. industr. Hyg., 3, 1-43
Wade, M.J., Lipkin, L.E., Tucker, R.v.l. & Fran, A.L. (1976) Asbestoscytotoxici ty in a long tenu macrophage- like cell cuture. Nature(Land. ), 264, 444-446
i\Tagner, J.C." (1963) Asbestosis in exriital animls. Brit. J. industr.~., 20, 1-12
\vagner, J.C. (1965) Th see1ae of exsure ta asbestos dust. An. N.Y.Acad. Sei., 132, 691-695
104
Wagner, J. C. & Be, G. (1969) ~othelioms in rats following inocationwith asbestos. Brit. J. Cacer, 23, 567-581
Wagner, J.C., Sleggs, C.A. & Mëchand, P. (1960) Diffuse pleural neo-theliom an asbestos exsure in the nort western Cape Province.Brit. J. industr. Me., 17, 260-271
Wagner, J.C., Be, G. & Timrell, V. (1973) ~sotheliomata in rats afterinoclation with asbestos and other materials. Brit. J. Cacer, 28,173-185
Wagner, J.C., Berry, G., Skidnre, J.W. & Timrell, V. (1974) The effectsof the inhlation of asbestos in rats. Brit. J. Cancer, 29, 252-269
Wagner, J.C., Berry, G., Coke, T.J., Hill, R.J., Poley, F.D. & Skidnre,J. W. (1977a) Anl exrimts with talc. ln: Walton, W.C., ed.,Inhaled Paricles and Vapours, IV, New York, PergaTn (in press)
Wagner, J.C., Berry, G. & Skidnre, J.W. (1977b) Studies of the cacino-genic effect of fibre glass of different diaiters following intra-pleural inocation in exintal anls. In: NIOSH Sysiumon Occupational Exsure ta Fibrous Glass, University of Maland,1974 (in press)
Wagner, P.A. (1928) Th Iron Deposits of the Unon of South Africa.Meir No. 26, Gelogical Surey, Pretoria, South Africa, CbverrntPrinting and Stationery Office, pp. 64-67
Wagoner, J .K. (1976) Ocupational cacinogenesis: the tw hnndred yearssince Percivall Pott. An. N. Y. Acad. Sci., 271, 1-4
Wagoner, J., Johnson, W.M. & Le, R. (1973) Maignt and NonrigntRespiratory Disease rbrtlity Patterns Arng Asstos ProductionWOrkers. ln: Congressional Record - Senate Proceeings and Detesof the 93rd Congress, First Session, 119, par 6, Washington OC,US Governt Printing Office, S-4660-S-4662
Wahlstrom, E. E. (1956) Introduction to Thretical Igneous Petrolog,New York, John Wiley and Sons, p. 6
Warock, M.L. & Churg, A.M. (1975) Association of asbestos and broncho-genic carcinom in a population wi th lCM asbestos exsure. Cacer,35, 1236-1242
Wester,1. (1973) Asstos and malignancy. S. Afr. ræ. J., 47, 165-171
Viler, H.W. (1943a) Asbestose nnd Lnngenebs. Dtsch. ræ. Wschr., 69,575-576
Weer, H.W. (1943b) UCr den Lugenebs bei Asstose. Dtsch. Arch.klin. Me., 191, 189-209
105
i'leh, H.J. & Plantholt, B.A. (1974) Asstos fibrils in beverages. 1.Gin. BulL. environm. Contam. Toxicol., 11, 267-272
Weiss, A. (1953)gesicher .
Pleurakebs bei Lnngenasbstose, in vivo norphologisch~izinische, ~, 93-94
Westlake, G.E., Spjut, H.J. & Smth, H.N. (1965) Penetration of colonicmucosa by asbestos paricles. An electron microscoic study in ratsfed asbestos dust. La. Invest., 14, 2029-2033
Whi ttaker, E. J. W. (1960) Th crystal chemstr of the arhibles.Acta cryst., 13, 291-298
Whttaer, E.J.W. (1963a) Chsotile fibrs, filled or hollow tubs?Chem. Eng. New, Septem, p. 30
Whittaer, E.J. W. (1963b) Asbestos. ln: Fibre Strcture, Chpter 18,lDndon, Buttei:rt, pp. 594-620
William, E. (1934) "Cuious boies" found in the lungs of col-workers.Lacet, ii, 541
Cacinogenc chemcals in foo as anJ. Air. veto ne. Ass., 164, 623-629
''lers, H. (1946) Tht Leislative ~æsures Have Prved C':ierally Effectivein the Control of Asbestosis, M.D. Thsis, Unversity of GlasgCM, UK
Wolff, A.H. & Oe, F.W. (1974)enviroruntal hel th issue.
Yada, K. (1967)microscope .
Study of chrsotile asbestos by a high resolution electronActa cryst., 23, 704-707
Yada, K. (1971) Poly-typ of strcture of chsotile obsrved by highresolution elecon llcroscopy. In : Proeegs of th 200 Inter-national Conference on Physics and Chstr of Asstos MieraIs,lDuvain" Belgium, 1971
Yazicioglu, S. (1976) Pleural calcification associated with exsure tochrsotile asbestos in southeast Tukey. Qist, 70, 43-47
Young, K. (1972) The Silent Pollutat, Distribution Septemr-Ctober,Dever, Co., Regiona Office VIII, US Depant of Real th, Educationan Welfare
Zielhuis, R.L., Versteeg, J.P.J. & Planteijdt, H.T. (1975) Pleura neso-theliom and exsure to asbestos. A retroSjcti ve cae-controlstudy in The Netherlands. Int. ¡'.rch. occu. environm. Hlth, 36, 1-18
Zielhuis, R.L., ed. (1977) Pulic Health Risks of :Esure to Asbestos,Euope Ecnomic Coity-Directorate of Soial Affairs, Cotract18-6- 1975 (in press)
Zussm, J., Brindley, G. W. & CC, J. J . (1957) Electron diffractionstudes of sertine mierals. AI. Mieral., 42, 133- 153
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EVALUATION OF CARCINOGENICRISK OF CHEMICALS TO MAN
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