Document v1xGa31865d5v941N9LdrxQw6

{ Atm. occvp. Hyg^ Voi. 45, Suppkmetf I. pp. 95-98,2002 > 2002 British Occupational Hygiene Society Pnbiahed by Oxford University Press DOb l&.1093/w4>yg/mdO Risk of Mesothelioma Among Women Living Near Chrysotile Mines Versus US EPA Asbestos Risk Model: Preliminary Findings M. CAMUS1*, J. SIEMIATYCKP, B. W. CASE2-3, M. DESY2, L. RICHARDSON2 and S. CAMPBELL2 'Science Affairs and Statistics Division, Health Canada 16881 me Durham, Montreal, Quebec H2C 2C8; 2INRS-lnstitut Armand-Frappier, 531 boulevard des Prairies, Laval, Quebec H7V1B7; }Departmeni ofEpidemiology, Biostatistics and Occupational Health, McGill University and Department ofPathology, Royal Victoria Hospital, 3775 University Street, Montreal, Quebec H3A 2B4, Canada Introduction. The risk of asbestos diseases cannot be measured directly in populations with low level chrysotile 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 Don-occupational chrysotile exposures. Methods. Female mesotheliomas first diagnosed from 1970 to 1989 in chrysotile asbestos mining districts (Asbestos and Thetford) 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-area-job-family 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 lo the population time-area-job-family exposure matrix and compared this predicted incidence with that actually observed. Results. Ambient airborne asbestos exposures were between 0.1 and 3 Ebrex/ml before 1970. The EPA asbestos risk model predicted 150 (range 30-750) female mesotheliomas in Asbestos, while only one case (peritoneal) was observed; 500 cases (range 100-2500) were predicted in Thetford Mines, while 10 cases (pleural) were observed. These large discrepancies cannot be explained by random or systematic errors. Keywords: amphibole; asbestos; chrysotile; cohabitation; linear carcinogenesis model; mesothelioma; neighbourhood; occupational exposure; risk assessment; tremolite INTRODUCTION AND BACKGROUND Cancer risk today at Tow' chrysotile asbestos expos ures (<1 fibre/ml in workplaces, <0.0005 fibres/ml in nan-occupational settings) cannot be observed by epidemiological or toxicological methods. Low risks must be estimated using quantitative risk assessments (QRAs) that extrapolate risks in past occupational cohorts (30-300 fibres/ml) to exposures today. Since 1980, regulatory authorities have conducted such QRAs to estimate cancer risks related to low asbestos Author 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 ail four studies, particularly for assessing the effects of chrysotile' (HEI-AR, 1991, chapter 6, p. 15), due to ill-defined concentrations of chrysotile and amphi bole mixtures. Moreover, the multistage model for exposure-risk modelling was fitted fully to 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 all-state legal* HWBUI0010302 96 M. Camus et al. recently. Between 1891 and 1980 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 chrysotile mining area (Siemiatycki, 1983; Camus and Siemiatyeki, 1998; Camus et at., 1998; Case et at., 2002). We here present preliminary findings of our validation study of the US Environmental Protection Agency (EPA) mesothelioma model. MATERIALS AND METHODS Core 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 materia] was 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 chrysotile mining districts (Asbestos and Thctford) at the time ofdiagnosis. These made up the observed cases. Risk assessment model and predictions The US EPA (Nicholson, 1986) used the asbestosmesothelioma risk model developed by Berry (Newhouse and Berry, 1976) and Pelo (Peto el ah, 1982): lM(r) -- Xy(t) = Km x c x [(r - tm - 10)3 - (r - tcaS - 10)JJ where X^t) is the standardized mesothelioma inci dence rate, is the gradient of ^(f) per fibre/ml, holding the lime parameters constant, and c is the asbestos fibre concentration [(fibres > 5 jtmymJ] between and t^. The model does not distinguish between pleural and peritoneal mesotheliomas despite their different aetiologies. The EPA estimated the linear exposure-risk gradient to be KM -1 O'8. 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 whole study population of the same birth cohort stratified by 5 yr periods and by mining district over the 1970-1989 period, itself stratified by S 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/nulling 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, 1 day fiber measure ments carried out annually by industrial hygienists since 1974 and two recent exposure surveys (Gibbs et of., 1980; Sdbastien et al., 1986). For earlier periods we assessed the 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 back 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 (Sdbaslien et al, 1989) to the lung burdens of 22 residents without occupa tional exposures (Case and SSbastien, 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 ~1 fibre/ml 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. We 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 -5% of local women had worked in the industry or had mended bags used HWBUI0010303 Mesothelioma n> women living near to chrysolite mines 97 for shipping asbestos. We estimated such past `occu pational exposures' to be-3-15 fibres/ml. 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 wc applied the EPA asbestos-mesothelioma model. the EPA based its estimates were exposed to substan tial levels of amphiboles, thereby tending to over estimate risks in chrysotile-exposed populations. Likewise, the risk could be greater in Thetford Mines than in Asbestos due to the greater iremolite content in some of Thetford'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 (168h/week)ora '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 females 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 et al (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 rates 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 per 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 that predicted by the US EPA model. Although risk assessments should be based 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 went 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; Siemiatycki and Boffetta, 1998). Amphibole fibres are more carcinogenic than chrysotiie fibres for mesothelioma. The cohorts on which Acknowledgements--The authors especially thank Drs Andrew Churg and Victor Reggli, who provided pathological reviews. Die Graham Gibbs, Morton Com and Patrick S dfcaslien and the late Dr William Nicholson who (with B.W.C) formed the expert exposure panel, Louise Nadoa, who assisted in data analysis, and Ms Marie Bcauchemin, who conducted the inter views of proxies for mesothelioma cases in Thetford Mines, Qudbec. This work was supported by a series of grants from Health Canada to Dr Siemizlycki, from NHRDP Canada to Drs Siemiatycki, Case and Patrick Sdbasdcn and by a giant from the Canadian Institutes of Health Research (CDiR) to Drs Case and Siemiatycki. REFERENCES Camus M. (1997) Why experts disagree about risks of cancer due to exposure to environmental asbestos. In Hercberg AM, Krupka I, editors. Statistics, science and public policy: hazards and risks. Kingston, Ontario: McGill -Queen's University Press, pp. 19-25. Camus M. (2001) A ban on asbestos must be based on a comparative risk assessment. Can Med Assoc J: 164:491-4. Cantus M, Stestialycki J. 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