Document xDMd1aGx34Z6z6B5p7B1Qe30

DPAIHMENT OF HEALTH. I~DUCATION, AND WELFAJU: I'IJIILIC tit 1\1. TU ~.t-:UVtC:l: NATIONAL "fOX I .OLOGl' I'UOGifl\11.1 r.o. uox 1:!?.:13 Rt:-:SEARCH TRIANGLE PJ.nK. N.C. 2770! Biological Effects of Ingested Asbestos Status Report January 22. 1981.. , .. : 'c;>-::~JiJ;' . * ICEH 5336 Code 9 43 44 45 46 56 72 80 Introduction The NIEHS is cond~cting a ~eries of studies on the effects of in~~sie~: .. asbestos. These studies are-part of the NIEHS commitment that is directed by the recently established National Toxicology Program. The Environmental Protection Agency has contributed approximately 10~ of the total funding~ A summar.y of the evolution of the study is to be found in Appendix .A. A .. paper, 91 ven at a Workshop on Asbestos, Gai thersb4rg, Haryl and, July 1977"; .'. detailing the studies design and implementation is attached (Appendix B)~ Current Status e,Test r~ateri al s - Two samples of chrysotil and single samples of amosite and crocioolite asbestos pius a tremolite material are being tested. A repository of these materials was established and has also served as a source for other scientific studies on asbestos. .. Each material has been extensively characterized as to physical and chemical pr:9.perties. The fiber size chara.cterization performed by the Illinois Institute of Technology Research ..Institute (IITRI), Chicago, Illinois, has been completed and a final report received. The"chemical and physical property characterization performed by the U~ S. Bureau of Mines is also completed. Hamster Studies Three asbestos materials are being studied at. liT Research Institute, Chicago, IL. The lifetime exposure phase of these experiments has been completed. There was no. indication- of major differences in the mortality rate between the hamsters receiving the asbestos diet or the control diet. Histopathologic examination of tissues from fema1e namsters has been completed. The contractor has reported that a preliminary ~nulysis of the hamster data indicates that no carcinogenic or cocarcino~ genic effect was observed. A standard independent quality review of the pathology results has been completed for the female hamster. A similar review of the male hamsters is in progress and is expected to be completed in March 1981. Analyses of the verified data and preparation of the draft report is in progress. The report is expected to be completed and sub- mitted to the NTP Board of Scientific Counselors Technical Report Sub- committee for independent public peer review in May 1981. ~ -1.. FMSI 04941 .... Rat Studie~ Five test materials are being itud~~d in. this spe~~es ~~the laboratories, Vienna:t virginia'. In addition, a subset of two studies ; ncl udes neonatal as \<Jell as 1i fetime ora1 expq_sure ~to asbestos.:. The .. lifetime exposure phase of the study has been completed. :Although data'~/'> has not yet been statistically analyzed, it appears that longevity \otas .. not affected by exposure to the various types of fibers, although the.':~: J.-.rtO\iO carcinogen (DHHL~i d ~igni fi~~t1y ..s.~_'!rtenl. i.fespar:t. The hi sto~ .; , pathologic phase of the study is in progress and is projected to be,.,:. completed in October 1981--there are a total of 5,158 rats to be examined. The hi stopathol ogfc eva1uati on is to be comp1 eted by group and then subjected to pathology quality review. Sequential issuance of final reports by asbestiform type .is. being considered with the first reports projected.' to be avail able for public peer revie\'1 in December 198l:.c;: ., . . .. ' . FMSI 04942 > Prom: ..,Biological Effects of t1ineral Fibres (Effets biologiques des fibres min~rales) Volume 2, Ed.: J.C. Wagner, International Agency for Research on Cancer Scientific Publications No. 30, Lyon, * IOmls369 Code 0 10 36 37 1980: 587-601. 38 70 ~ ,<> ' ,,:,~~J.f:*~,:~c~ J~-~r,. ~-'~ '~02:,~;.:,~ Y. ~l "'~'-, 7+..~ ' ; 90 81 ASBESTOS-RELATED DISEASE: -AN EPIDEMIOLOGICAL REVIEW .., , }~.;z:~::~fr:;;' c., ' , ., . > > . c:~:~~~.{~' ,:~.-[.:jt.:,__::'~ f ?t:i'tt~~:;~;?~,.~, L' '' J .c. Mc:IXImiD TUC Centenary Instit;ute of Occupational. HeaZ.th~ London School. of Hygiene and Tropical. Medicins~ London~ UK '' + ~- ,,..._ ,, Epidemiology is concerned with disease incidence, etiological. evidence and evaluation of control measures.. This review w:l.ll examine what has been achieved fn these three fields, focussillg on recomnendations on asbestos and cancer made to the UICC fn 1964 CDICC Working Group on Asbestos Cancers, 1965) and to the IARC fn 1972 (Bogovsld. et al., 1973) . Five of the six points which the epidemiological recOIIIIIII!!ldations of 1964 comprised were repeated fn 1972. Why the sixth, which related to the effects of exposure under different industrial and environmental conditions,. was omitted. is unclear, since it remains unanswered. The main concern in both lists was etiological, with some reference ~ 1964, and rather more in 1972, to questions of social impact and effectiveness of control. '.' It was natural that asbestos-related cancers should figure prominently in reports to the UICC and IARC. Epidemiological surveys of mortality, case-control or cohort, are more straightforward and 'easi"er to interpret than those required for the chrOnic and insidious manifestations of asbestosis. Certainly the information now avai"lable on the asbestos cancers is relatively more complete and so provides the main theme for this review. However, asbestosis will not be ignored, if only because its detection underlies several approaches to the prevention of both types of disease. The main issues to be considered are (l) whether or not asbestos exposure is a causal factor in the disease in question, (2) whether all fibre types are equally implicated, and {3) whether any other factors, personal or environmental, significantly modify the link between cause and effect. These three facets are interrelated and cannot be -587- FMSI 04943 588 On the central question of whether asbestos causes lung cancer there can now be little doubt. There is direct epidemiological evi- dence for the carcinogenicity of chrysotile, crocidolite, amosite and . anthophyllite (IAB.C, 1977); all the. usual criteria have been met (J.c. McDonald, 1980); and the view that. the risk was confined to smokers is no longer tenable (Hammond et al., 1979; McDonald et al., 1980). The relative potency of the.different fibre types is less clear, however, as is the form of interaction ~th tobacco smoking. Fiwe type All discussions on this subject are bedevil!~ by the 'problem of comparing like with like. Thus, even in the same industrial process at apparently similar dust/fibre levels, the distribution of particles by length and diameter may well vary with different types of asbestos. Add to this the extreme paucity of epidemiological surveys in which. there are any data whatever on dust or fibre concentrations, and it will be evident that only substantial differences in observed risk have much meaning. Moreover, for obvious reasons, similar industrial processes are seldom carried out with different types of asbestos or different mixtures. ,. Mining and milling (i.e., fibre production) have therefore been of particular interest; but, until recently, there have been no findings reported for comparisoa with Quebec chrysotile workers. Thus, the reports on crocidolite mining in Wittenoom, Western Australia, by Hobbs et al. 2 and in the Cape Province, South Afric.a, by. Talent et aL 3 are especially welcome. As the South African study was cross-sectional in type, only the Quebec and Australian findings can be compared directly:, and then wit~ some difficu1ty. The popu1ations studied differed socially, in entry criteria and in the mortality to date - 41% in Quebec and 8% in Western Australia. A comparison of those employed one year or more and followed at least 15 years from first employment (Australia), 1 See p .737 2 See p. 615 3 See p. 723 FMSI 04944 EPIDEMIOLOGICAL REVIEW 589 or 20 years (.Quebec),' appurs to show that the lung cancer experience of . the crocidol1.te miners was several times worse than tbSt of men who 'ffil produced chrysotUe: the standardized mortality rati.o (SMlt) in Quebec''JS~~.,a ... I; miners was 1.28 and that in miners in Western Australia, ..2.47.; Bowever;~4;;<~"*'. this c01Dparison takes no account of envi.ronmental conditi.ons, fibre ~;W:&~';lj!l:'t! , concentrations, type and duration of work, etc. Within the industries which work with asbestos, the position has, with few exceptions, been obscured by the use of m:f,xtures. Despite very short periods of exposure to Australian crocidolite - seldom in excess of 2! rears - the Nottingham and Canadian gas-mask workers (Jones et al. ; A.D. McDonald & J.C. MCDonald, 1978) both had about twice the number of lung cancer deaths expected. Amosite factory workers and several cohorts exposed to amphibole-chrysotile mixtures have also suffered very severely from thi.s di.sease (IAllC, ~977) ~~ c~ ~ ; "<, ' ; . c ; ,.. ' 0 ) ) Enterline & Henderson (1973) and Hughes & Weill2 both attempted the difficult task of separating the effects of di.fferent fibre types in factories where more than one was used. To the extent that thi.s was achieved, their studies also point to lower risks after exposure to chrysotile only, than after exposure to amphiboles or amphibole-contain- ing mixtures. . . ''"'"' "- ,," Apart from two small cohort studies reported by Elwood & Cochrane (1964) and Weiss (1977), there has been no information on factory workers exposed to chrysoti.le only. In the first-mentioned where, in fact, some crocidolite had been used, there were seven cases compared wi.th 3.02 expected; in the latter, the SMR for lung cancer was 0.93 (but only 0.61 for 'all causes'). The mortality of men 20 or more years after first employment in the Rochdale textile plant (Peto 3 ) may eventually provide more comparable data. At face value, the texti.le workers experienced a much higher excess mortality from lung cancer (30 deaths observed, 15.47 expected) than Quebec chrysoti.le miners at s:l.mi.lar exposure levels (.J .C. McDonald et al.~). However, crocidolite was also used at Rochdale, and there is still uncertainty about the fibre concentrations to which the men were exposed. ..,.. See P 637 2 See P 627 .3 See p 829 See P 811 FMSl 04945 590 Smoking J ~ -'*. ,. >7'i* ; ,/ ,_. -~ '"'it:'... ' In 1977, Saracci (1977) reviewed the nature of the asbestos-smoking interaction, as it affected the occurrence of lung cancer.:tJ' He identifi three simple models, though recognizing that there cotild oe others of greater complexity; these were: (1) that the. effects are independent' and simply additive; (2) that asbestos and tobacco act synergistical1y, perhaps even multiplicatively; and (3) that asbestos produces lung . cancer only in those who smoke_:. . :. ;;:YJJ; .~1!:;'-;:Ix;:;.lk' ~-~~1-,_%1 . ,: ; .~ ,;. With the data then available to him, he bad some difficulty in discarding model 3, found nothing to support the additive model, and tentatively concluded that the multiplicative model appeared the most plausible. It should- be noted that in none of the reports at his disposal were both asbestos exposure and smoking adequately quantified. Since then two further sets of results bearing on the question have become available. One based on the large cohort of North- American insulation workers (Hammond et al., 1979) gave relative risks which agreed perfectly with the multiplicative model, as below: Asbestos exposure Never Ever Never smoked Ever smoked 1 10.85 5.17 53.24 The other set of data, based on our most recent findings for Quebec chrysotile miners and millers (J. C. McDonald et al. , 1980) , appear more than additive but less than multiplicative: Nonsmokers Moderate smokers Heavy smokers Asbestos exposure : - i ::: :.:.L ;} .' -L-i-tt-l-e----M-~o-d-e-ra-te-----He-av-y-~-:,.;;~;~~~..:ll -'.i"w~"' 1 2.0 6.9.; .~- . ' '--'' ~~ ~~<..';!: :;:,~ " ... .,. 6.3 7.5 12.8 11.8 13.3 25.0 It may be too much to expect that a single biostatistical model will apply exactly in all circumstances. However, both studies agree on two important points: (1) that the re~tive risk for nonsmokers exposed to asbestos is at least as great as that for smokers and (2) that in absoZute terms most asbestos-related lung cancers occur in those who have smoked. FMSI 04946 EPIDEMIOLOGICAL REVIEW 591 Mesothe"Lioma Since Wagner and his colleagues (1960) reported a concentration of cases of mesothelioma in the crocidolite mi.ning area of the Cape Prov- ince, South Africa,.. epidemiological interest ha& foclissed on the impo~ " tance of fibre type.. This 1ed to para1lel ~esearch by phYsical and;, experimental scientists (see, for example, Pooley, 1973;. Timbrel!, 1973; Wagner & Berry, 1973), which has added greatly to the under-:~$' : standing of factorsthat influence the penetration of fibrous particles and the critical importance of shape and size. It was hardly a surprise that malignant mesothelial tumours would eventually be found ::.JW:'~ associated with other mineral fibres of the required dimensions (Baris et al., 1978, 1979). Clearly, asbestos substitutes must be viewed with fresh caution. In recent reviews of all cases of malignant mesothelioma reported to the end of 1975, including those in industrial and community surveys (J.C. MCDonald, 1978; J.C. McDonald & A~D. McDonald,_l977), the follow- ing conclusions were drawn: . . ..:':\.if~/ (1) The geographical distribution was uneven, with concentrations near dockyards and certain large asbestos plants. Elsewhere the incidence was low, perhaps approaching the 'background' level present before the commercial exploitation of asbestos. (2) Exposure to airborne crocidolite in man had clearly proved far more hazardous than that to chrysotile, although, in anima] experiments, the carcinogenic potential of all types of asbestos and other mineral fibres seemed similar. (3) The status of amosite was uncertain; the substantial incidence of mesothelioma in amosite factory workers conflicted with the apparent infrequency among amosite miners. From 1930 on, amoaite had been used for insulation materials in the USA; and from about 1950 it had become the major constituent. Possibly, this explained the high incidence ., among American insulators. ,. :" Papers submitted to this conference bring much further evidence on these issues. The cohort survey by Hobbs et al. 1 of Australian crocidolite miners identified 30 cases of mesothelioma, 17 (3.3%) among 519 ascertained deaths. The authors note an unusual absence of peritoneal tumours and, indeed, a deficit of abdominal tumours of all types. With only 8% of the cohort dead, it is too soon to est~te the eventual impact of mesothelioma. At a comparable stage in the Quebec chrysotile mining cohort study there had been no deaths from mesothelioma. 1 See p. 615 FMSI 04947 592 The survey of black South African crocidolite mineworkers by Talent et al. 1 is cross-sectional and therefore most difficult to interpret. ~t The very existence of prevalenCe rates for mesothelioma;.,..basea~ on some 68 cases detected in various defined ~oups, is disturbi!ig~i,"4 A IIIOst useful figure is that four cases were found in a representative saJiaple of 236 men examined 21 or more years after f:i.rst exposure .t.:~'ia":prev aleuce rate of 2%. For comparison, we estimated that the"'~averale e ' .prevalence of mesothelioma in Quebec chrysotile mineworkers 'during . years 1965-1977 was roughly 0.05%; and in Canadian gas-mask worbrs''14,f~:':,~.,;i during the years 1965-1976, between 1-2%. These estimates assume that'"~; i-;~~ cases of mesothelioma would be detectable two years before death." It " ;;~, may be recalled that in the Canadian gas-mask cohort, nine (16%) of 56 "" deaths to the end of 1975 were probably due to mesothelioma (A.D. McDonald & J.C. McDonald, 1978); in the current paper by Jones et al. 2 on Nottingham gas-mask workers, 17 (10%) of 166 deaths to the end of 1978 were ascribed to mesothelioma. ; An indication of the possible role of crocidolite is contained in the report by Rossiter & Coles3 au mortality in naval dockyard workers. In a cohort of 6292 employees followed to the end of 1978, there was a . total of 1042 deaths: 28 deaths were from mesothelioma, but only l.3 "'< deaths were from all other asbestos-related diseases. Thi.s suggests"' that the exposure to asbestos was not heavy but was particularly 'liable to cause mesothelioma. The use of crocidolite in the British Navy :.M could well explain this pattern. ,?r::-n>'t"'X-c '-4> .' The same issue is implicit in problems identified by Peto.. in his . paper on mesothelioma in the Rochdale factory. Although the employees are described as 'chrysotile asbestos textile workers', in fact, crocidolite was also used. Without electron microscopic analyses of lung tissue, data from this 'survey will remain difficult to interpret: An analysis is presented by A.D. McDonald 5 of the occupational histories of all known deaths from mesothelioma in the Province of . Quebec between 1960-1968, with special attention to cases dn persons exposed only to chrysotile in mines and mil1s and in workers employed in four factories, two of which had used crocidolite and one amosite for limited periods. There were 22 cases in the latter three factories:;;. compared Wi.th 10 cases from the mines and mills, where the workforce was some eight times larger. After exclusion of cases attributable to asbestos (almost all in men), the remaining incidence was similar in the two sexes and might conceivably have had some other etiology. ...,.': ':- ~ '< See P 723 2 See p. 637 .. See P 713 See P 703 5 See P 673 FMSI 04948 EPIDEMIOLOGICAL REVIEW 593 Lastly, two important sets of data describe results from Dr P' .D. Pooley's laboratory on the mineral fibre content of lung from cases of mesothelioma and controls obtained from (a) the 1976 national survey in the UK and (b) national surveys in the US and Canada in 1972~,:~t L11 the " first of these, reported by Jones et al ..c~, 108 cases (86 coufiriaectr' apd '56 'controls' were investigated. ''The authors were &Ware" tha.t. '1:heir'' ' 'controls' were unsatisfactory and may nat be wholly comparable' with the case series. In the North American study (A.D. li:Donalc12 ), 100 care- , fully matched case-control pairs were submitted to Dr Pooley,' and the results for 37 pairs are so far available. In both studies, the. labor- atory examined the specimens without knowledge of their provenance. The results from these surveys are shown side by side in Table , 1. In neither is there any difference between cases and controls in the distribution of chrysotile; the levels are considerably higher~: howeverP in the American series. In both studies amosite is present in much larger quantities, in the cases than in the, controls,, whereas crocid-. olite is more in evidence in the UK. These. findings reflect the relatively low levels of importation of crocidolite to North America and, indeed, the apparently lower incidence of mesothelioma on that;:;;: continent (J.C. McDonald &A.D. McDonald, 1977). The figures so far' available thus support the hypothesis, that amosite has played an impo%-- tant part in the etiology of American mesotheliomas and goes some way to cowiter the doubts expressed by Nicholson et al. 3 -- - - ..,. ,.; ,. ? ~. ,: ' :: Table 1- Distribution(%) of chrysotile, crocidolite'and amosite in lung tissue from mesothelioma cases and controls in North America and I , the_ United Kingdo~ F1bNS ( 101 ) Chrysot1le Crac1clllUte Mas1te 1 per 1 dried lung tis- Merica lilt Merica Ul Merica Ill cu.. Controls c.... Controls !!!! ~ ~ ~ .E!!!! ~ !!!! ~ N11 30 40 21 70 11 10 3t 31 54 20 61,.. . <1 ~~r-~1 < 10 I 10 < 100 11 15 .51 59 24 19 14 11 31 54 11 9 11 1t a0 50 30 :Ill 'D 21 20 11 'D 11 43 03 '"t~:>..: zt 31 11 0 11 0 ~1L looor_.. I 6 0a 0 0 13 4' 0 z " Nortll Merica - 37 case-cantrol pat" (A.D. lldlana14, p. Unit8d lt..,.._- 1118 cues - 5I aMtrOis (~ .tal., p. 637) ....' ~ 1 See p. 187 2 See p. 681 3 See p. 823. FMS\ 04949 594 MCDQNAU) Otizer. maZignancies. >'"~' ,;:.::'il.( ' ,+..,.:,_ J::;:"1;f~%c,, ; ~ -~~ .r~~~>:li~~<~~- ~i~--~~-Ji~,t;;-~::t~ Gastrointes-tinal. cancers.- Since those~ ~le' asb'estos fibres may .well swallow even more, it is reasonable to suppose that this might'Ci'*'; lead to malignant disease of the gastrointestinal tractJ >'I In some ~;~~1 industrial populations a substantial risk has 'been demonstrated, e.g;.:;:: in insulation workers in Belfast and in North America and in American'7'' amosite factory workers; in other groups, however, there has been no excess, e.g., in London factory workers, Finnish anthophyllite miners and Rochdale textile workers. The studies of Quebec chrysotile miners and millers have also been difficult to interpret; for example, there was substantial excess mortality from cancer of the oesophagus and stomach in the most heavily exposed men, but no systematic exposure- response relationship; and differences between the two main mining areas were not' readily explained by dust exposure. . - .. In a careful review of the subject, Miller (1978) concluded that, despite irregularities and inconsistencies, the weight of evidence pointed to a causal relationship, affecting all sites ill the gastro-'7' intestinal tract. He doubted whether further data of the kind antic- ipated would clarify the situation. There appear to be unrecognized f,: factors of importance, perhaps in the diet, which are not beirig taken into account: it is as though the effects of asbestos on the respiratory tract were being studied in ignorance of tobacco. Identification of the missing link could have similar importance. La.Pyngeal cancer.- Some studies have shown an association between asbestos exposure and cancer of the larynx; others have not. In the cohort of insulation workers studied by Selikoff et al. (1979), nine deaths were recorded, compared with 4. 7 expected. In London factory workers (Newhouse & Berry, 1973), there were two cases and 0.4 expected. In Quebec chrysotile workers (J.C. MCDonald et al., 1980), 17 cases were observed and 16.1 expected; however, there was a direct relationshipc here with smoking. An excess of laryngeal cancer in Italian chrysotile miners is difficult to interpret as the mine is located in a province. with a very high incidence of the disease (Rubino et al . 1979). A. case-control study in Liverpool by Stell & McGill (1973) showed a very "' high relative risk (14.5), but the inquiries were not made blind, and it is difficult to accept that only 3% of control subjects in that city had been exposed occupationally to asbestos. In a smaller case-control study in Toronto by Shettigara & Morgan (1975), also not made blind, an association was found with both asbestos exposure and smoking. Newhouse et al. 1 now report the results of a substantial case-control survey from the London area, based on living subjects. Neither patients nor interviewer were aware of the diagnosis at the time of the inquiry, and the control series seems particularly appropriate. The cancer patients smoked more heavily than the controls but had not been any more frequently exposed to asbestos. 1 See p. 687 FMSI 04950 EPIDEMiou:x;ICAL REVIEW , ~ '~ -:~~J~t;';;-~ ~, ,:;-_,..:~--~Li;~ ,~~~: ~ Othezo sites.- In the most -recent repo-rt by Sellkoff et al.. car1Ceron North Ame-rican~ ~ulation wrtte-rs,. 922 deaths f-rom recorded on death certi~icate, s,. c o m p 1<: ar e ' d ; with 13~9~,li"1'~*'",'!~-;. t,~d~ -f~;,?~\ . 602.3 respir excess, atory o 472.2 were asc-ribed r alimentarY tracts.. to.TmheerseotthheUliso. m-raeom&rinto~ac.a ncer "'excess 130.1 deaths f-rom mal.ignalr.t disease at other sites (SMa~.~:J.:9). : Review of 'best available information (autopsy, surgical., cl.irdkl.)~ reduced : the ratio to 1.4, but the effect of similar review o~ 811 death certif- icates in the us, f-rom which the 'expected' figures were calculated, is of course unknown. Indeed, it may be questioned whether nat:i.onal rates for a large country, such as the USA, provide a fair basis of comparison for a specific and unevenly distributed occupational group such as insulation workers. In our owD. cohort study of chrysotile miners and millers the comparable mortality from i:ancer at other sites .was: . observed, 304; expected, 285.8 (SMR,. 1.06). Whether there are other organs in which malignant disease is induced by asbestos must be consid- ered, but the diagnostic problems (see Selikoff et a1., .1979) seem well- nigh insuperable and the pathogenic mechanisms c o r r e s pon . ... d i n g l y....-\ obscure. Asbestosis Pulmonary and pleural fibf>rr-o-':s. is"'"''' hav~ been .._,_:t~-~h,~ coliliaml causes of dis-. . ability, and less f-requently of mortality, in asbestos workers i.n"'~y. countries (e.g., Lopez-Areal Del Amo 1 ). The early detection~~; removal from exposure of affected workers, biological monitoring systems '"" and the definition of hygiene standards, are preventive measures which all rely on epidemiological understanding. Considerable effort has .. been put in recent years into the development of radiological, physio- logical and clinical tests for the presence of disease manifestations and into standardizing them for epidemiological surveys. Even so, problems of inter- and intra-observer er-ror and subject variation remain enormous; the specificity and sensitivity of tests inevitably confli~t; .L and their validity. is largely unmeasured. Peto (1978), in discussing )~~;J~.:;: ,:. the lack of information on the prognostic significance of crepitations, ,g\~F states: 'if data on severe disability or death are sufficient to '' evaluate the significance of the sign, they wi11 al.so' be sufficient: to assess the serious risk directly, so there may be ~ttie advantage ~ considering the prevalence of such a sign in f-raming.~_'bYsiene standard'. This lack of information on prognostic significance applies to virtually every sign and symptom used in studies of asbestosis. The current paper by Liddell2 is therefore something of a landmark. It summarizes results of his more extensive studies on the relation between radiological findings in Quebec chrysotile workers while still employed and their subsequent mortality. While it is true that the findings ~' ' '< '"'- ~c, 0 k,-> ; See p. 201 2 See p. 667 FMSI 04951 s96 . i::: ;:~f:ll~f~~~~~. c.: ~ ,,:;;~~s;:i~i~ convincingly validate the UICC/Ci.DCinnati classification (and by inference, the. n.o U/C.:rsystem aiso)~ they do so in a relative'ra1:ne.r than in an absolute' sense:.';. ThU.~'''it Was the~use of the' cl&s................ scales by a specific' 8r0up""' of sii: readers. oQ. ...... unlqiie"" samitle" of" chest radiographs which was validated, rather than any particular Zevel of reading. Peto' s reservation therefore. stands: until~ si8ns and symptoms can be recorded and interpreted objectively; mertality"'may still be the most reliable basis for hygiene standards. ~ L ' ;<;r :1;;;~ Yll:. The paper submitted by Berry1 deals with validation of another kind, that of compensation procedures under the Industrial Injuries Act in the UK. As in a silll:Uar study some years ago (McVittie, 1965), the observed, mortality was between tfiO and three times expectation: 52% of; the excess was due~'to lUng 'cancer, 32% to asbestosis, 14% to mesothelioma and 3% to othei cancers. Despite the special nature of the study , material, the very low figure for gastrointestinal and other cancersis worth noting .. ..;......~ ; ...... ~ y: '" "> :::' ' The finding of pleural plaques in general populatil:ns raises anal.:. ~ ogous questions as to their significance. Localized areas of pl.eural :;~~;.~:;:;:; ... >-'thickening may or may not be calcified and calcified areas of pleura may . :1f" ;:f~J or may not be thickened. The endemic phenomenon in question is mainly r:~'/,"' one of 'calcified plaques r' and while they bave certainly occurred in<(: . areas where asbestos ..is found, they are also found elsewhere. Indeedt the evidence that there is any causal relationship between pleural ' calcification. and mineral fibre pezo se is unconvincing. Nevertheless.~ some environmental mineral, often closely associated -wtl:h asbestos deposits, must surely be implicated (see for example Gibbs, 1979). We certainly need to know more about the etiology and prognostic import.- ance of these mysterious changes. ..' ;.4~~' ::. ; ;:~ ~>, (!~_} . ;SOME METHODOLOGICAL POINTS;,~.,',"_";"!~i~~~)&~~~'>~~;~"''"" '1:~::'" ' Four papers in this section deal with problems whicb'may be loosely. classified as methodological. Lewinsohn et al. 2 describe preliminary.: ' phases in a sttidy of mesothelioma cases in the Connecticut Tumor Registry, .. which has still to overcome serious problems of diagnostic reliability ,, and in recor4ing asbestos exposure. Perdrizet et al. 3 discuss the objectives and achievements of the French mesotheliomaregister, init- iated in 1975. As a measure of disease incidence, the procedure .. See P 603 2 See p. 655 3 See P 697 f, ' FMSI 04952 EPIDEMIOLOGICAL REVIEW 597 . .;' failed to secure the universal collaboration of French pathologists. On the other hand, it; appears to be 1eading to a wider recognition of mesothelioma as a disease entity and to better diagnostic standard- .. ization. For all its imperfections, ..the authors believe that the. register will enable useful etiological observations to be made" specially if backed by tissue analyses. . Di Menza et al. 1 investigated the important question of whether valid information on past asbestos exposure is obtainable frODl micro-:.;; scopic examination of lung washings. Their data showed good correlation between the presence of ferruginous bodies and a definite history of exposure. Other relationships were inconclusive. More information might be obtained if time since last exposure were taken into account. Liddell's paper1 on latent periods in lung cancer mortality stems frODl the frequent suggestion that the period between first exposure and appearance of the tumour is related inversely to dose. His analysis, based upon the experience of Quebec cbrysoti.le workers, showed no evidence of this relationship. The question is of more than academic importance, since the presence of such a. relationship would greatly complicate efforts to define exposure-response models and to establish hygiene standards.. ~~c .,":"'' ;,l,t & IMPORTANCE OF CONTROL Faced with an environmental hazard, several strategies are possible: simple steps to minimize the effects, application of hygiene standards, or complete ban (with or without substitutes). The public and their governments make these decisions on the basis of their appreciation of what scientists tell them about vari.ous aspects of c:;ost and benefit . Epidemiology bas done much to identify and explain the health effects of asbestos - indeed feW environmenta1 problems have been studied so extensively; it bas not done so well in putting the risks into proper perspective or in evaluating the control options. It would be invidious to identify the incompetent and mis1eadng estimates and unfair to blame it all on the news media, vested interests or political pres- sures. The fact remains that more than 40 years after the introduction of hygiene standards and 15 years after the 1964 New York Conference, few if any industrial countries have reliable or comprehensive data on the health costs of asbestos, and there is next to no information on what control measures have achieved. There are a few exceptions; for example, Hammond et al. (1979) demonstrated that asbestos worker&wbo gave up smoking had substantially lower death rates than those who . : continued. Or again, Becklak.e et al. (1979) studied the effect of removal of asbestos workers from further exposure, with less encouraging results. The need for better data on the importance and effectiveness of control is a challenge for epidemiological research. See p. 609 2 See p. 661 FMSI 04953 ' 598 ~,~~~~:;:;~F~L-- ;tJ-~~,l~;-~df.' Several important etiologi~- questions seem DOW settled. Lung cancer is caused by all kinds of asbestos,:. wi.thout for any other factor. The interaction between smoking and asbestos is at least additive and in some circumstances multiplicative. The amphiboles appear to carry a higher risk of lung cancer than chrysoti1e; however, there are sti11 no comparable data on exposure-response relation-: ships with different fibre types or in various industrial circumstances. The risk of mesothelioma after chrysotile exposure appears small, and most asbestos-related cases are probably due to crocidolite or amosite. A low incidence of this tumour, of unknown etiology, antedated the commercial -use of asbestos and probably coutiuues:,!fw,,tThe implications of fibre size and shape, rather than type pe:r --Be, deserve attention. The causal association with other cancers ~ notabiy_ of- the upper gastrointestinal tract and larynx - is less consistent and suggest a role for other unidentified factors. A major difficulty in the study of the pleural and parenchymal. changes of asbestosis lies in the standardization of tests and in " defining their prognostic significance. The ILO U/C radiological classification has now been validated in terms of mortality in chryso~ tile workers, but the findings cannot be generalized. The etiology and-, significance of pleural calcification is still unknown. The present and future impact of asbestos-related disease on the community remains controversial, and few estimates are based on adequately representative data. Evidence of the effectiveness. of environmental ana other control measures is equally deficient. _t '. ,_. Il semble que plusieurs questions etiologiques importautes scient mainteuaut resolues. Le cancer du poumou est provoque par toutes les varietes d'amiaute sans que !'intervention d'un autre facteur soit necessaire. Les interactions entre l'usage du tabac et l'amiaute sont pour le moins additives et. dans certains cas; multiplicative&. Les amphiboles paraissent comporter un plus fort risque de cancer du poumon que le chrysotile; mais il n'existe toujours pas de donnees comparables sur les relations exposition-effet avec different& types de fibres ou dans diverses situations industrielles. FMSI 04954 .. EPIDEMIOLOGICAL REVIEW 599 :~;;:_:c > ,. - > ' Le risque de mesotbeliome apres exposition au chrysotile semble faible, et 1a plupart des 'Cis lies~ a l' amiante sont probablement dus a . 1 la croc:idolite ou a 1' amosite. . .. Une. faible incidence de cette . i::umeur, ::.:4..! d' etiologie inc:onnue, precedait 1 'utilisation commerciale de 1. '~ante.;.:;.tf~< ;')~7~ et subsiste probablement. I.es effets de 1a taille et cle.la.forme del! ~:i11'1:{:';y,:'2:' fibres, plutot que de la varied elle-meme, miritent attention. I.'asso~ ciation causale avec d'autres cancers - ceux des voies digestivessupe~ rieures et du larynx notamment - est mains reguliere et laisse supposer !'intervention d'autres facteurs non identifies. L'une des grandes difficultes de !'etude des lesions pleurales et parenchymateuses dues a l'amiantose reside dans la normalisation des~ tests et 1a determination de leur signification pronostique. La clas- sification radiologique BIT U/C a maintenant ete V&lidie en ce qui concerne la mortaliti des travaill~urs exposes au crysotile, mais on ne saurait generaliser ces observations. I.' etiologie et la signification de la calcification pleurale demeurent inc:onnues ~ :. .. \.,.,<;, '. "" . t :~.:- .- . - .-~~~.:;~.<::_,::---_:..~,~: . ~ :..:{.;.}" Les repercussions actuelles et futures des maladies liees a l'amiante sur la collectivite restent matiere a controverse, et peu d'estimations reposent sur des donnees suffisamment representatives. I.es indices de 1' efficacite des mesures de lutte enyironnementales ou autres sont . egalement insuffisants. .. .. Baris, Y.I., Sabin, A.A., Ozesmi, M., Kerse, I., Ozen, E., Kola~an, B., AltinOrs, M. & GOktepeli, A. (1978) An outbreak of pleural meso!;helioma and chronic fibrosing pleurisy in the village of Karain/ . Urglip in Anatolia. Thora:::, 33, 181-192 Baris, Y.I., Artvi.nl.i., M. & Sahi.n, A.A. (1979) Environmental mesothelioma in Turkey. Ann. N.r. Acad. Sci.:~ 330, 423-432 Becklake, M.R. L:i:ddell, F.D.K. Manfreda, J. & McDonald, J.C. (1979). Radiological changes after withdrawal from asbestos exposure. BP. J. ind. Med., 36, 23-28 Bogovski, P., Gilson, J.C., Timbrel!, V. & Wagner, J.C., eds (1973) BioZogicaZ Effect;s of Asbes"tos (IARC Scien"tific PubU.cat;ions No. 8), Lyon, International Agency for Research on Cancer, pp. 341-346 Elwood, P.C. & Cochrane, A.L. (1964) A follow-up study of workers from an asbestos factory. Br. J. ind. Med., 21, 304-307 FMSI 04955 600 t'COCl'W.D T" :f-,, :". ~r :-. Enterline, P.E. & Henderson, V. (1973) tory cancer in the asbestos indUstey~ 312-317 Gibbs, G.W. (1979) Etiology of pleural calcification: Quebec chrysotile asbestos miners and millers. HeaZth6 34, 76-83 Hammond, E.C., Selikoff, I.J. & Seidman, H. (1979) Asbestos exposure, cigarette smoking and death rates. Ann. N.Y. Aaad. Sci. 6 330, , 473-490 .; IARC (1977) IARC Monogzoaphs on the EvaZuation of the Carcinogenic iI Risk of ChemicaZs to M:zn, Vol. 14, Asbestos, Lyon, International ' Agency for Research on Cancer . -~ a ;,,:.:. , ; ;: ~ McDonald, A.'n." &-.lknoria!d~ J.C. (1978),, Mesothelioma after croddolite I exposure during gas-mask manufacture. Environ. Res:~~l?~ 340-346' . '. 4:..~~....-->~iH';,4,~p-"~- _;;';~ McDonald, J. c. (1978) &r:posuzoe reZcrti.onships and malignant mesotheU.oma. .: ' .. I In: Glen, H.W., ed., Pr-oceedings of Asbestos Synrposi.um6 Johan:rtssbuxtg~. -~: I 1977, Randburg, National Institute for Metallurgy, pp. 6]...,]9 ,~::tJ~:?~;.i..;~.:': , McDonald,. J .c. (1980) . .. *' .;j;;..~,-; ,1':,. ~.,_ Asbestos and lung cancer-: has the caseoeen :''~~/f:{;, :, -:, _,~~/t, . <i:, proven? Chest (in press) :,>E.:... ,<.;,::.. : :: j :"i:<~--~ McDonald, J .c. & McDonald, A.D. (1977) Epidemiology of mesothelioma . ~-.~'; ,,..,".: from estimated incidence. Prev. Med. 6 6, 426-446 McDonald, J.C., Liddell, F.D.K., Gibbs, G.W., Eyssen, G.E. & McDonald,. A.D. (1980) Dust exposure and mortality in chrysotile mining, 1910-75. Bzo. J. i.nd. Med. 6 37, ll-24 McVittie, J .C. (1965) Asbestosis in Great Britain. Ann. N.Y. Aaad. Sci., 132, 128-138 Miller, A.B. (1978) Asbestos fiber dust and gastrointestinal ~g~ nancies. Review of literature with regard to a cause/effect rela- tionship. Newhouse, M.L. J. chron. Dis., 31, & Berry, G. (1973) 23-33 Asbestos and laryngeal ~!~c'aH~.n"c"e'''r'-".' _:"'f;...~;.;. ~ Lancet;, ,ii, 615 .,. ~ ;~_ :~,:~:_:t~~?.. . ,,. ". Peto, J. (1978) The hygiene standard for chrysotile asbestos . Lancet~ i, 484-489 ,. t , - , ; Pooley, F.D. (1973) MesotheUoma i.n reZati.on to e:r:posuzoe. In: Bogovski, P., Gilson, J.C., Timbrel!, V. & Wagner, J.C., eds, BioZogi.caZ Effects of Asbestos (IARC Scienti.fi.c PubUcations No. 8), Lyon, International Agency for Research on Cancer, pp. 222- 225 Rubino, G.F., Piolatto, G., Newhouse, M.L., Scansetti, G., Aresini, 'G; A. & Murray, R. (1979) Mortality of chrysotile asbestos workers at the Balangero Mine, Northern Italy. Bzo. J. i.nd. Med. ~ 36, 187-194 J,. I fMSl 04956 .. EPIDEMIOLOGICAL REVIEW .~-f'';'.:::. . 601 Saracci, R. (1977) Asbestos and lung cancer: an analysis ~I epidemiological evidence on the asbestos-smoking 1n~eJ"ac:~1.on. Int. J. Ca:ncn11 20, 323-33~ Selikoff, I..J., Hammond, E.C. & Seidman, H. (1979 Mortality expei-1..:... ences of insulation workers in the United States and c;anada, 1943- . . 1976. Ann. N.Y. Aead. Sci. 11 330, 91-116 Shettigara, P.T. & Morgan, R.W. (1975) Asbestos, smoking and laryngeal cancer. Arch. environ. Hea"Lth11 30, 517-519 ..Stell, P.M. & McGill, T. (1973) Asbestos and laryngeal cancer. .Lancet11 ii, 416-417 ' ., ,.. ,. . '. Timbrell, V. (1973) Physica1. faoto'Z's as etiotogicaZ mechanisms. In: Bogovski, P. , Gilson, .J.C. , Tim.brell., V. & Wagner, .J. C. , eds, Biotogicat. Effects of Asbeatos (IARC Scientific Publications No. 8) , Lyon, International. Agency for Research on Cancer, pp. 295-303 UICC Working Group on. Asbestos Cancers (1965) Report. BZ'. J. ind. Med. 11 22, 165-171. . Wagner, J.C. & Berry, G. (1973) InfOZ'I'I'1ation obtained fzoom animal e:r:pezoiments. In: Bogovski, P., Gilson, J.C., Tim.brel1, v. & Wagner, J.C., eds, BiotogicaZ Effects of Asbestos (IARC Scientific PubUcations No. 8), Lyon, Internationa1 Agency for Research on. Cancer, pp. 285-288 Wagner, J.C., Sleggs, c.~. & Marchand, P. (1960) Diffuse pleural meso- thelioma and asbestos exposure in the North Western Cape Province. Bze. J. ind. Med. 11 17, 26Q-271 Weiss, W. (1977) Mortality of a cohort exposed to chrysotile asbestos. J. oaaup. Med. 11 19, 737-740 .I i ' FMS\ 04957