Document nV2E01LMnRQwkYvE2oLz8b56

<vSi5Kft> ggS I PATHOLOGY AND EXPERIMENTAL PATHOLOGY Pathologic Reactions to Chrysotile and Their Mineralogic Correlates Andrew Churg This presentation briefly considers the correlations between pathologic reactions to chrysotile and the corresponding mineral content of the lungs. Most of these comments on the effects of chrysotile are derived from the analysis of the lungs of a series of Quebec chrysotile miners and millers, and a comparison group of shipyard workers and insulators with amphibole exposure. It should be appreciated, however, that there exists considerable epidemiologic evidence, and some mineralogic ev idence, which suggests that processed (milled) chrysotile ore has different biologic properties.1 Thus comments that apply to disease seen in chry sotile mining industry workers may not hold true for individuals with other types of chrysotile exposure. * FATE OF CHRYSOTILE IN THE LUNGS A variety of studies have made it clear that chrysotile and amphiboles differ markedly in their ability to concentrate in lung tissue. Wagner el al.2 hy/e shown experimentally that, in rats constantly exposed to am phiboles, fiber concentration in the lung steadily increases; but with exposure to chrysotile, there is only a brief increase in chrysotile con centration, and this is followed by a leveling off of concentration. Whether this phenomenon reflects proximal deposition in airways be cause of the curled shape of the fibers, dissolution of the fibers in lung tissue juice, or extremely rapid macrophage-mediated fiber removal, is unclear. In any event, mineralogic analysis indicates that a similar phe nomenon must occur in humans. For example, Wagner ft al.3 showed chat, in a series of workers with exposure to both chrysotile and amosite or crocidolite, the amphibole concentration averaged 100 times the chrysotile concentration at the time of examination. I have observed a similar effect in shipyard and insulation workers from the Pacific North west of North America (Table 1). PLAINTIFF'S I EXHIBIT CIIR-225 ! The same process ers. Most of these \ crocidolite, but were e> (referred to, fof convc very minor constituent no pathologic evidence exposure of about 30 ) X 106 fibers/g dry lun) fibers/g dry lung, a tre In a group of chrysoti was about 10:1 (see re that pulmonary tremol exposure than chrysoti the possibility that the in disease. DIFFERENCES AS A FUN OC Much less is know workers exposed to var ucts. We examined a set Tasie 1. Asbe I Population 95th Percentile for 20 males fi the general population ol Vancouver' 7 Long-term resident! of Thet never employed in the asbe! industry1* 9 Thetford chrysotile miners a millers with no asbestos-reL . lung disease* 9 Thetford chrysotile miners a millers with only airway fibrosis' 10 Thetford chrysotile miners millers with asbestosis M Shipyard and insulation workers with asbestosis 5 Thetford chrysotile miners a millers with mesothelioma* 52 Shipyard and insulation workers with mesothelioma not asbestosis * Fibers X 10*/g dry lung. -wr -* * r. t: The same process also occurs in Quebec chrysotile industry work ers.4,5 Most of these workers have not been exposed to amosite and crocidolite, but were exposed to the amphiboles tremolite and actinolite (referred to, for convenience, as tremolite) which form a natural but very minor constituent of the chrysotile ore. In a group of workers with no pathologic evidence of asbestos-related lung disease and an average exposure of about 30 years,5 the mean chrysotile concentration was 23 X 106 fibers/g dry lung and the mean tremolite concentration 58 X 10` fibers/g dry lung, a tremolite-to-chrysotile ratio of about 2:1 (Table 1). In a group of chrysotile workers with mesotheliomas, the mean ratio was about 10:1 (see reference 6, Table 1). These observations suggest that pulmonary tremolite burden may serve as a better marker of total exposure than chrysotile in chrysotile industry workers, and also raise the possibility that the tremolite component of the ore may play a role in disease. DIFFERENCES IN PULMONARY CHRYSOTILE FIBERS AS A FUNCTION OF DIFFERENT TYPES OF OCCUPATIONAL EXPOSURE Much less is known about the chrysotile content of the lungs in workers exposed to various forms of processed (milled) chrysotile prod ucts. We examined a series of 21 workers exposed in shipyard, insulation. Tarle 1. Asbestos Fiber Concentrations in Various Populations' Population Chrysotile Tremolite Amosite 4 Crocidolite 95th Percentile for 20 males from the general population of ^Vancouver' / Long-term residents of Thetford never employed in the asbestos industry10 9 Thetford chrysotile miners and millers with no asbestos-related lung disease* 9 Thetford chrysotile miners and millers with only airway fibrosis' 10 Thetford chrysotile miners and millers with asbestosis 14 Shipyard and insulation workers with asbestosis 5 Thetford chrysotile miners and millers with mesothelioma4 32 Shipyard and insulation workers with mesothelioma but not asbestosis 1.0 (Mean 0.3) 1.7 23 47 74 0.5 64 0.7 1.0 (Mean 0.4) 5.3 58 106 143 0.9 540 0.8 0.01 0 0.06 0.23 0.10 31 0 5 * Fibers X 10'/g dry lung. Values are means except as noted. ..ffigzu I m1 ! $ 56 Accomplishments in Oncology textile, friction products, and manufacturing industries, and found, by comparing fiber concentrations in the workers to concentrations in a nonexposed population, that tremolite as well as chrysotile nytst have been present in the various end products.7 The pulmonary ratio of tremolite-to-chrysotile in Quebec chrysotile industry workers is fairly constant;s,` however, in workers exposed to processed products, the ratio varies widely and the marked residual predominance of tremolite is not seen in their lungs,7 suggesting that processing of the original fibers for different commercial applications results in removal of tremolite from the final product. If tremolite really is important in the genesis of me sothelioma, the relative lack of tremolite may account for the virtual absence of mesotheliomas in those exposed to chrysotile in the textile and friction products industries. One additional interesting point which emerged from this study was the observation that there were marked differences in the sizes of chry sotile and tremolite fibers found in workers with exposure in different types of industries. The shortest fibers were found in shipyard workers; the longest in textile, brake, and manufacturing workers; and fibers of intermediate length in insulators. It is possible that these length dif ferences will be found to correlate with epidemiologic evidence of dif ferent disease rates in different chrysotile-using industries.* Incidentally, analysis of fiber length proved to be the most reliable method of de termining mineralogically whether an individual had been exposed to chrysotile by breathing urban air or in an asbestos-using occupation; fibers in the occupationally exposed group were distinctly longer (Table 2). RELATIONSHIP OF ASBESTOS FIBERS IN VARIOUS POPULATIONS TO DISEASE PATTERNS Table 1 shows concentrations of chrysotile and tremolite in various chrysotile-exposed populations, and a comparison group of amosite and crocidolite-exposed shipyard and insulation workers. Because, as noted, everyone in the population is exposed to all these forms of asbestos by breathing urban air, reference ("background") values for the general population of Vancouver are also recorded. A number of interesting conclusions emerge from these data. One conclusion is that, on average, increasing amounts of fibrosis in the lung are associated with increased burdens of chrysotile/tremolite, a finding Table 2. Geometric Mean Fiber Lengths (urn) in Various Populations Population Chrysotile Tremolite General population of Vancouver' Long-term Thetford resident*" Thetford chrysotile miners and millers' Workers exposed to processed chrysotile' 1.3 2.4 2.5 2.5 1.6 2.1 2.1 2.5 I I I i which has previousl t cidolite,2 but not sh< data with regard to Another ftnporte exposure, chrysotile in humans. There is of pleural mesothelii I during the period 19 14I ponents and no amos i f sotile ratio and the ' {Ij mesothelioma is stri with only fibrosis, an olite in the genesis o An additional ol disease is seen at mi I crocidolite compared J that much less amosi required to produce e even applies to those olite seen in the serie in Table 1 would, if t range for both mesol mine dust appears to whether this is also trt The epidemiologic evi implies that such fibe A last conclusion, to current controversy very low levels of asbi from the data shown town of Thetford Mi: industry.10 These indi years to a lifetime. Th were elevated some 10 of Vancouver, a popuh of background atmosp! thermore, the mean siz were considerably Ion but were quite similai workers (Table 2). Nont disease, and a variety c that there is no increat idents of the asbestos therefore, that asbesto considerably longer (a: than those carried by t which has previously documented in those exposed to amosite'and cro- cidolite,* but not shown for chrysotile. We are currently analyzing this data with regard to severity of asbestosis. Another important conclusion is that, at sufficiently high levels of exposure, chrysotile ore must be judged capable of causing mesothelioma in humans. There is no other explanation for the fact that, of six cases of pleural mesothelioma in Thetford chrysotile workers analyzed by us during the period 1980-1984,` five contained only chrysotile ore com ponents and no amosite or crocidolite. The very high tremolite-to-chrysotile ratio and the very large lung burden of tremolite in those with mesothelioma is striking when compared to those with no disease or with only fibrosis, and certainly raises the possibility of a role for trem olite in the genesis of mesothelioma. An additional observation is that, for any of the diseases listed, disease is seen at much lower pulmonary concentrations of amosite/ crocidolite compared to chrysotile/tremolite (Table 1). Thus it appears that much less amosite/crocidolite compared to chrysotile/tremolite is required to produce either asbestosis or mesothelioma. This conclusion even applies to those with no disease: the levels of chrysotile and trem olite seen in the series of nine chrysotile miners without disease* cited in Table 1 would, if the fibers were amosite and crocidolite, be in the range for both mesothelioma and asbestosis. Thus Quebec chrysotile mine dust appears to be relatively innocuous. It is unclear, however, whether this is also true of certain types of processed chrysotile products. The epidemiologic evidence in regard to the textile industry in'particular implies that such fibers may be considerably more dangerous.* A last conclusion, and one which is particularly interesting in regard to current controversies in North America about the dangers of inhaling very low levels of asbestos in public buildings such as schools, emerges from the data shown in Table 1 on seven long-term residents of the town tff Thetford Mines who were never employed in the chrysotile industry.10 These individuals lived in Thetford for anywhere from 25 years to a lifetime. Their mean chrysotile and tremolite concentrations were elevated some 10 to 15 times over those of the general population of Vancouver, a population which is probably reasonably representative of background atmospheric exposure to asbestos in North America. Fur thermore, the mean sizes of fibers in the lungs of the Thetford residents were considerably longer than those of the population of Vancouver, but were quite similar to the fibers found in the chrysotile industry workers (Table 2). Nonetheless, these individuals had no asbestos-related disease, and a variety of epidemiologic studies have shown quite clearly that there is no increased incidence of mesothelioma in long-term res idents of the asbestos mining townships.' The data just cited imply, therefore, that asbestos burdens composed of considerably more and considerably longer (and, hence, theoretically more dangerous) fibers than those carried by the general population of North America do not 58 Accomplithmenti in Oncology produce disease. These observations should produce reassurance about the lack of danger from exposure to very low levels of asbestos in public buildings or urban air. SUMMARY In chrysotile industry workers, tremolite concentration exceeds chrysotile concentration by large ratios. In those exposed to processed chrysotile products, tremolite is also present, but the chrysotile-to- tremolite ratios in the lung suggest that tremolite is removed in milling the chrysotile ore. Chrysotile and tremolite concentrations are higher in those with asbestosis than those without. Analysis of lung tissue indicates that chrysotile mine dust can induce mesothelioma in humans, but extremely high lung burdens appear to be required for this process. In such workers, the ratio of tremolite-to-chrysotile is much higher than & in those with parenchymal fibrosis, raising the possibility that tremolite 1.< is important in the genesis of mesothelioma. For both mesothelioma and asbestosis, the disease appears at much lower lung burdens of amosite/ crocidolite than chrysotile/tremolite. Long-term residents of Thetford Mines, a chrysotile mining town, carry lung burdens that are composed of more fibers and longer fibers than residents of most North American 'j cities, but residents of the town of Thetford who have not worked in the chrysotile industry do not have elevated lung cancer or mesothelioma rates. These observations imply that the burden of asbestos which the general population carries as a result of exposure in public buildings will not produce disease. ,. ACKNOWLEDGMENT t Supported by grants MT6907 and MA7820 from the Medical Research Council of Canada and grants from the National Cancer Institute of Canada. REFERENCES lVMcDonald JC, Liddell FDK, Gibbs GW, Eyssen GE, McDonald AD. Dust exposure and mortality in chrysotile mining, 1910-1975. BrJ Indus! Med 1980; 37:11-24. 2. Wagner JC, Berry G, Skidmore JW, Timbrel! V. The effect of the inhalation of asbestos in rats. Br J Cancer 1974; 29:252-259. 3. Wagner JC, Pooley FD, Berry Cttol.A pathological and mineralogica) study of asbestosrelated deaths in the United Kingdom in 1977. Ann Occup Hyg 1982; 26:423-431. 4. Rowlands N, Gibbs GW, McDonald AD. Asbestos fibers in the lungs of chrysotile miners and millers: A preliminary report. Ann Occup Hyg 1982; 26:411-415. 5. Churg A. Asbestos fiber content of the lungs in patients with and without asbestos airways disease. Am Rev Respir Dis 1983; 127:470-473. 6. Churg A, Wiggs B, DePaoli L, Kampe B, Stevens B. Lung asbestos content in chrysotile workers with mesothelioma. Am Rev Respir Dis 1984; 130:1042-1045. 7. Churg A. Fiber size and number in chrysotile miners, users of processed chrysotile ore, and members of the general population. Am J Indust Med 1986; 9:143-152. 8. Becklake MR. Occupational lung disease: Past record and future trend using the asbestos case as an example. Clin Invest Med 1983; 6:305-317. 9. McDonald JC. Health implications of environmental exposure to asbestos. Environ Hlth Perspec! 1985; 62:319-328. 10. Churg A. Lung asbestos content in long-term residents of a chrysotile mining town. Am Rev Respir Dis 1986; 134:125-127. t Pulmonary F in Chrysoti Francis H. Y. ( John Dem .Asbestos exposure increased mortality frc pleural and peritonea the gastrointestinal tr asbestos-associated di asbestos type and thei In recent years, tl estimate risks for asb dose-response scale.1 from mortality data re; inaccurate compared l fatal conditions. Asbes thus, it may nut be ret mortality data have pi atively low levels of tempted to increase th observing pathologic proach enables detect significance but woult pathogenesis of asbesl derived from a cohort viously studied epider determining exposure old level) and in demot we present correlation mulative exposure, an M The Workplace and Esti; The plant under s terials for steam engim