Document 7MK4dgR5b25x0OqyvE91w2G06

Aim Ilyjf,, Yul. -(&v>iiip|)K'ih-,iii L pjk U> Wr IIKf* <>2tf)lUrilidiOwvp*uwil Myptoe StKiujr ruMUtal hsrOxfivd Univemity Prw DQt; 11),1OW/untvhygAncfM 1 Risk of Mesothelioma Among Women Living Near Chrysotile Mines Versus US EPA Asbestos Risk Model: Preliminary Findings M. CAMUS1*, J. SIEMIATYCKI2, B, W. CASE3*3, M. DESY2, L. RICHARDSON2 and S. CAMPBELL2 1Science Affairs and Statistics Division, Health Canada 10881 rue Durham, Montreal, Quebec H2C 2G8; 2lNRS-lnstihtt Armartd-Frappier, 531 boulevard des Prairies, Laval. Quebec H7V IB7;3Department ofEpidemiology, Biostatistics and Occupational Health, McGill University and Department of Pathology, Royal Victoria Hospital, 3775 University Street, Montreul, Quebec H3A 2114, Canada Introduction. The risk of asbestos diseases cannot be measured directly in populations with low level chrysolite asbestos exposure. Risk assessments must be used to extrapolate risks from past heavy Industrial asbestos exposures to today's low chrysotile exposures. We tested the US Environmental Protection Agency (EPA) mesothelioma risk model In a population baring experienced relatively high and mostly non-occupational chrysotile exposures. Methods. Female mesotheliomas first diagnosed from 1970 to 1989 in chrysotile asbestos lutniug districts (Asbestos and Thctford) were Identified from the Quebec Tumour Registry and hospital records gathered throughout the province. Diagnoses were reviewed by three pathologists. An International expert panel estimated historical ambient exposure levels In these districts. A 'time-arca-job-famlly exposure* matrix Was derived from these estimates, occupational and cohabitation exposure estimates and a survey of 817 female residents. We applied the EPA mesothelioma incidence model to the population timc-aroa-Job-fimilly exposure matrix and compared this predicted incidence with lhat actually observed. Results. Ambient airborne asbestos exposures were between 0.1 and 3 tibrcs/ml before 1970. The EPA asbestos risk model predicted ISO (range 30-750) female mesotheliomas in Asbestos, while only one case (peritoneal) was observed; 500 cases (range 100-2500) were predicted In Thetrord Mines, while 10 cases (pleural) were observed. These large discrepancies cannot be explained by random or systematic errors. Keywords: nmphibalc; asbestos; chrysotile; cohabitation; linear carcinogenesis model; mesothelioma; neighbourhood; occupational exposure; risk assessment; tnuuolilc INTRODUCTION AND BACKGROUND Cancer risk today at 'low' chrysotile asbestos expos ures (<t fibre/mt in workplaces, <0.0005 fibres/ml in non-occupational settings) cannot be observed by epidemiological or toxicological methods. Low risks must be estimated using quantitative risk assessments (QRAs) lhat extrapolate risks in pest occupational cohorts (30-300 flbres/ml) to exposures today. Since 1980. regulatory authorities have conducted such QRAs In estimate cancer risks related to low asbestos Audior to whom correspondence should be addressed. exposures, targeting mixtures of chrysotile and amphiboles (Nicholson. 1986;HEI-AR, 1991). Regarding mesothelioma, up to four occupational studies have been used for exposure-risk analysis. Unfortunately, `there are serious weaknesses in all four studies, particularly for assessing the effects of chrysotile'(HEI-AR, 1991, chapter C, p, 15). due to ill-defined concentrations of chrysotile and titophibole mixtures. Moreover, the multistage model for exposure-risk modelling was fitted fully lo only one cohort (Peto el al, 1982). The uncertainly of the model is thus large, yet usually discounted. A small region of Canada's Province of Quebec produced most of the world's asbestos until 1954 and remained the world's largest asbestos exporter until 95 96 M. Cumus ct uf. recently. Between 1891 and I960 asbestos fibre emissions and fallout were visible; residents experi enced exposures intermediate between those of past asbestos workers and those of today's urban popu lations. We undertook a research programme to quan tify risks and specify risk factors for asbestos-related diseases in women residing in that chrysolite mining area (Siemiatyckl. 1983; Camus and Sicmiatycki, 1998; Camus etal., 1998; Case etal., 2003). We here present preliminary findings of our validation study of the US Environmental Protection Agency (EPA) mesothelioma model. MATERIALS AND METHODS Case ascertainment We visited hospitals throughout the populated portion of Quebec province. We identified, from hospital records, oncology archives and pathology records, all women aged 30 years or more for which a possible mesothelioma was mentioned in their chart between 1970 and 1989. Diagnosis was reviewed by two pathologists for subjects for whom we could obtain pathological tissue blocks or slides. We accepted all cases classified as 'definite', 'probable' or ' possible' mesothelioma by either of the two pathologists or, if pathology material wns unavail able, by an algorithm based on a 10 point clinical rating score by a third pathologist (B.W.C.) (Case et at., 2002). Through hospital records and interviews of relatives we identified all possible mesotheliomas (pleural or peritoneal) in females residing in Quebec's chiysotilc mining districts (Asbestos and Thetford) at die lime of diagnosis. These made up the observed eases. Risk assessment model and predictions The US EPA (Nicholson, 1986) used the asbestosmesotheiioma risk model developed by Berry (Newhouse and Berry, 1976) and Peto (Peto et of, 1982); - \iW * x c x [(r - rMn - 10)5 - (r - ^ _ 10)J] where X^t) is the standardized mesothelioma inci dence rate, JCM is the gradient of XM(f) per fibre/ml, holding the time parameters constant, and c is the asbestos fibre concentration [(fibres > 5 ttm)/ml] between and f(nil. The model docs not disli nguish between pleural and peritoneal mesotheliomas despite their different aetiologies. The EPA estimated the linear exposure-risk gradient to be tH = 10-*. We applied this model to the exposure histories of the study population. We estimated asbestos exposure levels for each year of a person's lifetime and esti mated the risk for each person surveyed. This risk was then applied to the whale study population of the same birth cohort stratified by 5 yr periods and by mining district over (he 1970-1989 period, itself stratified by 5 yr periods. Historical exposure assessment Asbestos exposure levels in 'fibres/ml' were esti mated for each year and mining town, according to the methods described previously (Camus et at., 1998), and for each of 'three possible exposure circumstances; (i) neighbourhood exposure resulting from asbestos mining/milling emissions; (ii) 'cohabit ation' exposure resulting from dust brought home by asbestos workers; (iii) occupational exposure. The only `hard data' on airborne asbestos levels in the asbestos towns were continuous dust measure ments carried out since 1972, I day fiber measure ments carried out annually by industrial hygienists since 1974 and two recent exposure surveys (Gibbs ef at., 1980; Sdbasticn et ai, 1986). For earlier periods we assessed (he following indirect evidence. 1. Annual production volumes by mining town from 1900 to 1984. 2. Historical information of the industrial and min ing processes. 3. Extrapolations hack to 1900 of the relation between airborne levels, annual production and controls in 1972-1984. 4. Past visible asbestos depositions estimated from a survey of 817 elderly female residents. 5. Aerosol dispersion modelling to estimate air borne asbestos levels in the town of Asbestos before the onset of dust controls. 6. Application of the relation between lung burden and occupational exposure histories of Quebec miners and millers (Sdbastlen et at, 1989) to the lung burdens of 22 residents without occupa tional exposures (Case and Sdbastien, 1989) to estimate their past exposures. 7. Review of these data by a panel of five experts to estimate past `neighbourhood exposures' in the three main mining towns for each calendar year since 1900. Average annual ambient levels would have peaked at -l fibre/m! between 1940 and 1954. The panel thought that true concentrations must have been less than three times smaller or greater than their best estimates. Seventy per cent of the women had lived with an asbestos worker. Wc derived `cohabitation exposure' estimates from a set of 10 autopsies of residents who lived with asbestos workers. We estimated cohabit ation exposures to be 0.1-1.5 fibres/ml above neigh bourhood levels. External sources corroborated these estimates. Our 1989 survey showed that -55b of local women had worked in the industry or had mended bags used Miuclhcliamii in women living newId chrysolite mines W for shipping asbestos. We estimated such past `occu pational exposures' to be-3-15 fibres/mt. Finally, in 1989 we surveyed a representative strati fied sample of 817 elderly female residents in the study agglomerations about their lifetime residential, occupational and cohabitation exposure histories. Combining these histories with estimated past exposure levels, we estimated a historical townyear-exposure matrix to which we applied the BPA asbestos-mesothelioma model. the BPA based its estimates were exposed to substan tial levels of ampbiboles, thereby tending to over estimate risks iu chrysotile-exposed populations. Likewise, the risk could be greater in Thetford Minos than in Asbestos due to the greater tremolite content in some of Thelford's mines (McDonald and McDonald, 1997). Another possible explanation is that the model itself may be wrong in form or in its parameter estimates. Finally, the exposure-effect relationship may be non-linear. RESULTS The average cumulative exposure of the study population from all sources was 25 fibres/ml yr (168 h/week) or a 'worker-equivalent exposure' of 105 fibres/ml yr [plausible interval (PI) 21-525 fibres/ml yr). Over the 1970-1989 study period the study base totaled 221375 person yr, for which the EPA model predicted 150 (PI 30-750) mesotheli omas in remates in Asbestos and 500 (PI 100-2500) in females in Thetford Mines. In comparison, a single mesothelioma (peritoneal) occurred in the Asbestos district. Ten mesotheliomas (all pleural) were observed in females in the Thetford Mines district. More detailed exposure information is given in Case trial. (2002). The risk of mesothelioma (pleural and peritoneal) was overestimated 150-fold (PI 30-750) in the Asbestos area, 35-fold (PI 7-175) in the Thetford Mines area and 50-fold (PI 10-250) in both areas combined. The mesothelioma incidence rales were 67.5 per million person yr in the Thetford area (95% Cl 32.4-124.1 per million person yr) and 13.7 per million person yr in the Asbestos area (95% Cl 0.35-76.2 per million person yr). In comparison, mesothelioma incidence among Quebec women was about 4 pci million person yr. DISCUSSION AND CONCLUSIONS We observed an excess of mesotheliomas in this population relative to the female population of Quebec. Still, the observed Incidence was orders of magnitude smaller than (hat predicted by the US EPA model. Although risk assessments should be bused on conservative or precautionary assumptions, a two order of magnitude overshoot for chrysolite expos ures could be an overkill that would hinder risk management if it wont unrecognized, particularly when comparing the risks of chrysolite to the risks of substitute fibres (Camus, 2001). There are several possible reasons for the discrep ancy between the EPA and our observations and between the risk in Asbestos and Thetford Mines (Camus, 1997; Siemiaiycki and Boffetla, 1998). Amphibotc fibres are more carcinogenic than chryso lite fibres for mesothelioma. The cohorts on which AcktwvrUilgemtmit--The authors especially thunk Dn Andrew Churg and Victor Roggll, who provided pathological reviews, Dre Graham Gibbs, Morton Corn and Patrick Sihtstiw and the late Dr William Nicholson who (with B.W.C.) formed (he expert exposure panel, Louise Nadon. who assisted la date analysis, and Ms Marie Beauchemin, who conducted (he inter views of proxies for mesothelioma eor in Thetford Mines, Quebec. This work was supported by a scries of grants from Health Canada lo Dr Siemiaiycki, from NHRDP Canada to Drs Siemiaiycki, Case and Patrick Sdfcostlen and by a grant from Uiq Canadian Institutes ofHealth Research (CIHR) lo Das Case and Siemiaiycki. REFERENCES Camus M. (1997) Why expert* disagree about risks of cancer due (exposure lo environmental asbestos, In Hwzberg AM* Knipko 1, editors. Statistics, science and public policy: hazard* and riskt. Kingston, Ontario; McGilKJueen'a University Press, pp. 19-25. Camus M. (2001) A ban on asbestos must be based on a comparative risk assessment. Cun Mod Assoc J; 164:491-4. Camus M, Siemiaiycki J. (1998) Nonoccupationol exposure lo chrysotiJc asbestos and the risk of lung cancer idler iresponse], N Engl J Med; 339: JOOZ. Cantus M, Siemiaiycki J, Meek 8. (199B) Ncnaucupdionnf exposure to chrysolite asbestos and the risk of lung cancer. NBngIJMcd; 3311: 1563-7j. Case BW, Sdbastien P. (1989) Fibre levels in lung and correla tion wilhtirsamplcs. In Bigncm J, Pcio J, Saracci R, editors. IA8C monographs on the evaluation of carcinogenic risk to humans: no. 90. Non-occupational exposure to mineral fibres. Lyon, France; International Agency for Research on Cancer, pp. 207-18. Case BW, Camus M, Richardson U Parent M-, Dday M, Siemiaiycki J. (2002) Preliminary findings forpleural meao* ibcUoma among women in die Quebec chrysolite mining regions. Ann Occup Hyg; 46 (suppl. O; 128-31. 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