Document jNjbxby9mXw5R5OkvB1B7Jw9Z

Pergaroon PII: S0005-4878(98)00007-6 Ann necup Hs'* Vru <2. So I. pp } 5. I9W i' lYir, Rnmh (Vv-p-ii.'itj1 Mumcik Published by Elsevier S^rrst-T L:J V!! rschs rtNcrvrd r- -o. 'r, (i'.mi HrU'i: Invited Editorial Unfinished Business: The Asbestos Textiles Mystery J. CORBETT MCDONALD Department of Occupational and Environmental Medicine, National Heart and Lung Institute, Imperial College. Dovehouse Street. London Sff3 6LY, U.K. It would be naive to hope, let alone suggest, that in consequence of the recent papers published in Annals on the Quebec chrysotile cohort--the most recent in this issue--that peace may now break out between the warring factions of `chrysophiles' and `chrysophobes' (see McDonald and McDonald. 1997). There are encouraging signs, nevertheless, that the distance between the two camps is less than it used to be; it now- seems fairly widely accepted that the car cinogenicity of the amphiboles, crocidolite in particu lar. is appreciably greater than of chrysotile and that contamination of the latter by fibrous tremolite may w ell have a disproportionate effect. There is also prob ably general agreement that the very high risks of lung cancer among workers in the manufacture of asbestos textiles have yet to be convincingly explained. This gap in knowledge is serious for until the mystery is resolved the future industrial use of mineral fibres-- natural or man made--must be subject to a nagging uncertainty. We would be wise therefore to examine this question in some detail. The problem first came to light in 1983 with the publication in that year of two independent cohort mortality studies (Dement et al., 1983a part 1; Dement el a!.. 1983b part II; McDonald cl al., 1983a) with closely similar findings on exposure response for lung cancer among employees of an asbestos textile plant in Charleston, South Carolina. This was the plant, incidentally, from which an autopsy on an employee gave the first evidence of a link between asbestosis and lung cancer (Lynch and Smith. 1935). The study by Dement el al., was of a cohort of 1261 white males employed for one month or more between 1940 and 1975. There were 35 deaths from lung cancer before the end of 1975 for a SMR against US rates of 1.50; 29 of the 35 occurred twenty or more years after initial employment (SMR 3.39). The study of McDonald el Received 19 December 1997. al., was of a cohort of 2545 men. black or white, employed for one month or more between 1938 and 1958 followed to the end of 1977 by which time there had been 66 deaths ascribed to lung cancer. The over all SMR was not calculated but among men employed twenty years or more there were 59 lung cancer deaths; taking account of race, the SMR against South Carolina rates was 2.00. The differing constitution of the two cohorts, and of the mortality ones used for reference were quite sufficient to explain the relatively minor difference in lung cancer SMRs. Of greater importance was the fact that in both studies exposure response relationships were inves tigated with almost the same results. Not surprisingly the exposure estimates used in the two studies were also similar since both had essentially the same base, namely over 5000 impinger samples taker, since 1930 by the Metropolitan Life Insurance Company (1930-- 1939). the US Public Health Service (1968-1971) and the company itself from 1930 onw ards. Dement ei al.. 1983a. (part I) estimated the relevant exposure levels to range from 3 to 78 fibres cc with typical levels well above 10 fibres cc. although these estimates were all obtained by conversion from dust particie measure ment (mpef)- Apart from the preparation area where a conversion factor of 8 was used. 2.5 was applied elsewhere. In the study of McDonald et al.. no con version from particle to fibre counts was attempted. Instead, for comparison of the two studies, both SMRs and RRs (relative risks) were calculated in relation to accumulated exposure (mpcf.y) for white men only, 15 years or more from first employment. The resulting relationships were essentially linear and expressed by quite similar equations, thus:- Dement et al., RR = !+0.069 mpcf.y; McDonald et al., RR = 1 +0.051 mpcf.y Apart from very small amounts of amosite acquired for experimental purposes in the late 1950s and less than 2000 lbs of crocidolite yarn imported annually at one location from the early 1950s until 1972. only chrysotile, mainly from Thetford Mines. Quebec. L>;;. HWBUI0007963 4 J. C- McDonald also from Rhodesia, was used in the plant during the relevant period. That these findings were specific to asbestos textiles manufacture and probably to chrysotile is supported by two other cohort studies in this industry. In parallel with the Charleston survey, another very similar in design was made at a plant in Mannheim, Pennsyl vania, owned by the same company, which used mainly chrysotile but also small quantities of amosite and crocidolite (McDonald et al., 1983b). The exposure response relationship for lung cancer mortality at Mannheim (RR = 1 +0.051 mpcf.y) was virtually identical to that in Charleston (RR = 1 +0.059 mpcf.y) but, whereas only one death from mesothelioma was observed in the latter, at least 14 were noted in the former. Less easily compared with these two investigations of American textile plants was that by Peto et al. (1985) of the textile factory at Rochdale. This factory which also used mainly Canadian or Rhodesian chrysotile, but an important amount of crocidolite in addition, gave very similar findings for both lung cancer risk and mesothelioma incidence to those from Mannheim. At the time of publication of these various studies it was immediately clear that the slope of the exposure response lines for lune cancer in the textile industry was some 50 times steeper than that observed in Quebec chrysotile miners and millers where exposures were very much higher and for whom an equation of RR = 1 +0.016mpcf.y for lung cancer risk had been estimated (McDonald et al., 1980). Various possible explanations were considered of which the main were errors in exposure estimation in mining and milling and/or textile manufacture, differences in fibre size distributions, differences in smoking habit, and con ceivably the effect of mineral oils sometimes used in textile plants for spraying to reduce dust and to facili tate spinning. However, with the possible exception of the last mentioned, none of these explanations seemed capable of reducing the difference in risk to below 10 fold. In contrast, it was evident that the mystery applied to lung cancer only; certainly at Charleston where no important amount of commercial amphiboles were used, the one case of mesothelioma in over 500 deaths from all causes (2/1000) was entirely in line with the 10 cases from nearly 5000 deaths from all causes (2/1000) in the Quebec cohort (McDonald et al., 1980). Since the discovery of the problem in the early 1980s, additional information has come to light which has done more to clarify the mystery than to explain it. It is now fairly clear, for example, that so far as chrysotile exposure is concerned, textile manufacture is the exception; available data for asbestos cement and friction products manufacture all approximate to that for mining and milling (Hughes, 1994). The mortality experience of both the Charleston cohort (Dement el al., 1994) and Quebec cohort (Liddell et al., 1997) have been updated and if anything estimates of lung cancer risk in the former have increased and in the latter decreased (see also Stayner et al.. 1997). On the other hand, there were now two mesothelioma deaths out of 1259 from all causes (2 1000) m the Charleston cohort compared with 38 of 8009 (5 1000) in the Quebec cohort (McDonald et al., 1997). More revealing, however, are two investigations using lung burden analysis. In the first of these (Sebastien et al., 1989), 161 lung tissue samples taken at necropsy from cohort members--72 from Charleston and 89 from Thetford Mines. Quebec--were analysed by trans mission electron microscopy. Statistical analyses of asbestos fibre concentration in lung tissue, with allow ance for duration of employment and time from last employment to death, indicated that the Quebec/ Charleston ratios for chrysotile concentrations were even higher than those for estimated dust exposure (mpcf). After allowance for the fact that the pro portion of tremolite in dust was estimated to be higher in Thetford Mines than in Charleston, the Quebec/ Charleston ratios for tremolite were much the same as for chrysotile. Altogether over 4000 chrysotile and tremolite fibres were identified and their length and width measured. With the exception of tremolite fibres over 20 pm in length, the distributions of lengths and widths for both fibre types were closely similar for the two cohorts. Of 175 tremolite fibres from Charleston. 4 (2.2%) were longer than 20/an compared with only 1 of 405 (0.2%) from Thetford--a difference easily due to chance. The other fibre burden study, published very recently (Green et al., 1997), entailed the analysis of lung tissue taken at autopsy from 54 members of the Dement cohort from Charleston and, for comparison, 34 other autopsies adequately matched for sex, age, hospital and year of death. The geometric mean con centration of chrysotile fibres per microgram of dried lung was higher in cohort members (33.45) than refer ents (6.71) and, of tremolite, much higher (3.56 vs. 0.26). There was also some evidence in the asbestos w orkers that fibre concentration was related to a score of fibrotic changes graded on tissue sections, with tremolite providing a better prediction of fibrosis than chrysotile. In the absence of denominators and times since last exposure and obvious uncertainty about the representativeness of this small series, further interpretation is difficult. In summary, then, we have strong and consistent evidence that in terms of exposure response the risk of lung cancer, but not of mesothelioma, was much higher--perhaps 50 times higher--in textile workers than in workers in mining and milling, or in the manu facture of asbestos cement or friction products, for all intents and purposes all exposed only to commercial chrysotile. There is nothing to suggest that the esti mates of cumulative exposures in the relevant cohorts were seriously in error although questions of peak exposures and fibre size distributions in ambient air have not been examined. There remain two hypoth eses, neither of which are well supported, the first concerning fibre length and the other the use of min- HWBUI0007964 f :r ft'i' 1997). o mesothelioma , (2Jttg) in the iofMBs/iooo) ai,rff/), More ations using lung (Sebastien et al., at necropsy from :on and 89 from alysed by trans;tical analyses of issue, with allowtd time from last nat the Quebec/ centrations were :d dust exposure ct that the prolated to be higher ;on, the Quebec/ much the same 00 chrysotile and their length and of tremolite fibres ns of lengths and :!y similar for the rom Charleston, npared with only difference easily published very d thjgkalysis of f of the . for comparison, bed for sex, age, netric mean conrogram of dried 33.45) than referhigher (3.56 vs. ; in the asbestos related to a score ie sections, with n of fibrosis than nators and times rtainty about the series, further 1 and consistent esponse the risk ioma, was much,,__ i textile workers or in the manuproducts, for all y to commercial est that the estirelevant cohorts lestions of peak s in ambient air ain two hypothportj^Mte first - thewHp min Invited Editorial. Unfinished business: the asbestos textiles mystery 5 eral oil spray. If fibre length is responsible theiTthe recent evidence (McDonald and McDonald. 1997) that the carcinogenicity of commercial chrysotile lar gely depends on its tremolite content must be taken into account. From the findings of Sebastien et al. (1989), it is clear that the dust to which textile workers were exposed contained relatively lower proportions of tremolite than that experienced by mine workers. Ofcourse, this might not be true of very long tremolite fibres (i.e. >20 pm) so a study to evaluate this possi bility has now been initiated. Acceptance of this hypothesis, however, would have two implications: first, that long fibres determine the risk of lung cancer but not of mesothelioma; second, that such fibres are specific to the textile process since they would other wise surely have been present in sufficient quantity in the much higher airborne dust levels of the Quebec mills. The mineral oil hypothesis also has its problems. Spraying was not used in the Rochdale plant until 1974 and it seems probable that persons employed before then were already at high risk of lung cancer. In the Charleston plant, an attempt was made by Dement et al. (1994) to assess risk among employees in relation to probable level ofoil contamination. This analysis showed only a twofold difference at most but, as oil spray was applied very early in the process, the extent to which levels of exposure were correctly assigned is open to doubt. It has also been stated that mineral oils have not been shown to induce lung cancer in workers exposed to machining oils (Stayner et al., 1997). It is known, however, that cheap oils of varying quality and purity were used, and there is evidence that some such oils have probably caused lung and skin cancer in both the UK and the USA (1ARC, 1987). Thus we are left with an unexplained mystery of very considerable scientific and practical importance which directly affects the future use of both natural and manmade mineral fibres. The question was ident ified epidemiologically 15 years ago and despite fur ther studies remains unsolved. Without a far greater contribution from physical scientists--including occu pational hygienists--on qualitative and quantitative differences in the nature of the relevant exposures and of experimental toxicologists in testing potential hypotheses, the question may never be answered. REFERENCES Dement, J. M. et al. (1994) Follow-up study of chrysotile asbestos textile workers: cohort mortality and case-control analyses. Am. J. Ind. Med. 26,431-447. Dement, J. M. et al. (1983) Exposures and mortality among chrysotile asbestos workers. Part 1: exposure estimates. Am. J. Ind. Med. 4, 399-419. Dement, I. M. el ai. (1983) Exposures and mortality among chrysotile asbestos workers. Part 11: mortality. Am. J. Ind. Med. 4,421-433. Green, F. H. Y. et al. (1997) Exposure and mineralogical correlates of pulmonary fibrosis in chrysotile asbestos wor kers. Ocatp. Ear. Med. 54, 549-559. Hughes, 5. M. (1994) Human evidence: lung cancer mortality risk from chrvsotile exposure. Ann. occup. Hrg. 38, 555-- 560. IARC Monographs. (1987) Supplement 7. pp. 252-254. Liddell, F. D. K. etal. (1997) The 1891-1920 birth cohort of Quebec chrysotile miners and millers: development from 1904 and mortality to 1992. Ann. occup. h'yg. 41, 13-36. Lynch. K. M. and Smith, W. A. (1935) Pulmonary asbestosis III: carcinoma of the lung in asbestos-silicosis. Am. J. Cancer 24, 56-64. McDonald. A. D. et al. (1997) Mesothelioma in Quebec chrysotile miners and millers: epidemiology and aetiology. Ann. occup. Hyg. 41. 707-719. McDonald. A. D. et al. (1983) Dust exposure and mortality in an American chrysotile textile plant. Br. J. Ind. Med. 40. 361-367. McDonald. A. D. et al. (1983) Dust exposure and mortality in an American factory using chrysotile, amosite, and crocidolite in mainly textile manufacture. Br. J. Ind. Med. 40, 368-374. McDonald. J. C. et al. (1980) Dust exposure and mortality in chrysotile mining. 1910-75. Br. J. Ind. Med. 37, 11-24. McDonald. J. C. and McDonald. A. D. (1997) Chrysotile. tremolite and carcinogenicity. Ann. occup. Hyg. 41, 699705. Peto, J. et al. (1985) Relationship of mortality to measures of environmental asbestos pollution in an asbestos textile factory. Ann. occup. Hyg. 29, 305-355. Sebastien. P. et al. (1989) Respiratory cancer in chrysotile textile and mining industries: exposure inferences from lung analysis. Br. J. Ind. Med. 46, 180-187. Stayner. L. et al. (1997) Exposure-response analysis of risk of respiratory disease associated with occupational exposure to chrysotile asbestos. Occup. Env. Med. 54,646652. HWBUI0007965