Document 8VNN7EXJYBjOm9M7g3pv9Y1RZ

American Journal of Industrial Medicine 14:241-243 (1988) LETTER TO THE EDITOR Response to Dr. Dunnigan's Commentary It would be inappropriate and presumptuous of me to comment on testimony in litigation and the consequent outcome, as addressed in the commentary of Dr. Jacques Dunnigan (1988). A discussion of the question posed by Dr. Dunnigan is a most appropriate subject for an expanded dialogue in the Journal. Clearly, the role of chrysotile in the pathogenesis of mesothelioma is an important health and public policy issue. Dr. Dunnigan summarized the relevant epidemiological information most appropriately. Succinctly stated, a substantial body of recent epidemiological evidence fails to establish an association of mesothelioma with exposure to commer cially processed chrysotile, although a small number of cases have developed among miners and millers of chrysotile ores in Quebec, Canada [McDonald et al., 1980; Churg et al., 1984], It is unclear whether the occurrence of mesothelioma in these workers is, in fact, unique to this asbestos mining region, for studies in Italy [Rubino, 1979], South Africa [Wagner, 1966], Soviet Union [Kogan et al., 1972], and China [Craighead, unpublished data] fail to demonstrate an increased prevalence of mesotheliomas among miners in these countries. The contemporary literature suggests, but does not prove, that a contaminant of some chrysotile ores, tremolite asbestos, causes mesotheliomas in miners and millers in Canada [Churg et al., 1984; Pooley et al., 1986; Churg, 1986]. This claim is based largely on circumstantial evidence, i.e., the prevalence of mesotheliomas among persons environmentally exposed to tremolite in Cyprus and Greece [Yazicioglu et al., 1980; Wagner, 1986; Langer et al., 1987] and the occurrence of a few cases of mesothelioma among vermiculite miners in Montana [Amandus et al., 1985], Of course, there are other possible explanations and the issue will remain unresolved in the absence of long-term epidemiological studies conducted on populations exposed to pure tremolite. Since knowledgeable scientists might disagree on this issue, it seems appropriate to maintain an open, objective posture, while additional informa tion accumulates. Animal studies are of little assistance in resolving the question. Although tremolite causes mesotheliomas in rats [Wagner et al., 1982], anthophyllite asbestos, fiberglass, and aluminum "whiskers" also induce tumors in animals [Stanton et al., 1972; Stanton, 1981]. These latter materials are not believed to cause mesotheliomas in man. The experimental work does demonstrate that a variety of fibrous materials Address reprint requests to John M.Craighead, MD, Chairman. Department of Pathology, The University of Vermont, Medical Alumni Building, Burlington, VT 05405-0068. Accepted for publication February 12, 1988. 1988 Alan R. Liss, Inc. 242 Craighead possess the capacity to produce neoplastic responses in the body cavities of animals having the features of mesotheliomas in man [Craighead, 1987], The mineralogy of tremolite is complex, for particulates vary considerably from nonfibrous to asbestiform in aspect ratio [Craighead, 1987]. If the Stanton hypothesis is correct [Stanton et a!., 1972; Stanton, 1981], only those tremolite fibers with high aspect ratios would be expected to produce tumors in man. It is generally assumed that the cruder forms of tremolite are removed during the milling of chrysotile [Churg et al., 1987], However, recent analytical studies indicate that tremolite fibers accumulate in the lungs of those who work with processed chrysotile [Pooley et al., 1986; Churg, 1986]. With possible exceptions, workers in these occupational groups have not developed mesothelioma. While the tremolite fibers are similar to tremolite in Canadian chrysotile ores, the concentrations in the lungs of workers are substantially lower than those found in the lungs of miners, millers, and residents of mining towns in Quebec. Assuming the correctness of these observations, the evidence argues either against a role for tremolite in the induction of mesothelioma, or for a threshold below which tremolite has no capacity to produce mesotheliomas (regardless of the aspect ratio and configuration of the fibers). Commercial amphibole asbestos clearly is the major cause of mesotheliomas in the United States today [Craighead, 1987]. However, the issue of a mesothelioma threshold for amphibole asbestos is an important, unresolved matter. The EPA's claim that thresholds do not exist for asbestos, regardless of type, is a posture based on regulatory, not scientific considerations. The available data do not allow one to calculate a definable threshold but substantial circumstantial epidemiological evi dence suggests that there are, in fact, thresholds below which mesotheliomas do not develop. In view of the exceedingly rare occurrence of an alleged mesothelioma in individuals working with processed, commercial chrysotile (and the background of exposure to commercial amphiboles in many of these cases) [Berry, 1986], I conclude that exposure to processed chrysotile has not been shown clearly to cause mesothe liomas. This conclusion is obviously contrary to widely publicized Federal policy, but it is clearly consistent with the existing scientific data. It is unfortunate that scientific considerations have not played a more important role in establishing public policy. John M. Craighead, MD Department of Pathology, The University of Vermont, Burlington, VT 05405-0068 REFERENCES Amandus HE, Wheeler R, Armstrong B (1985): Mortality of vermiculite miners exposed to tremolite. In "Sixth International Symposium on Inhaled Particles." pp. 81-82. Berry G (1986): Chrysotile and mesothelioma. In Fortner JG, Wagner JC, (eds): "In Accomplishments in Oncology, The Biological Effects of Chrysotile." Philadelphia: J.B. Lippincott Co., pp. 123-132. Churg A (1986): Pathologic reactions to chrysotile and their mineralogic correlates. In Fortner JG, Wagner JC, (eds): "Accomplishments in Oncology, The Biological Effects of Chrysotile." Philadelphia: J.B. Lippincott Co., pp. 54-58. Churg A, Wiggs B (1987): Letter to the editor. Am J Ind Med 12:117-118. Response to Dr. Dunnigan's Commentary 243 Churg A, Wiggs B, Depaoli L, Kampe S, Stevens B (1984): Lung asbestos content in chrysotile workers with mesothelioma. Am Rev Respir Dis 130:1042-1045. Craighead JE (1987): Current pathogenetic concepts of diffuse malignant mesothelioma. Human Pathol 18:544-557. Craighead JE, Akley NJ, Gould LB, Libbus BL (1987): Characteristics of tumors and tumor cells cultured from experimental asbestos-induced mesotheliomas in rats. Am J Pathol. In press. Craighead JE, Kleinerman J, Abraham JL, Gibbs AR (1987): Diseases associated with exposure to silica and non-fibrous silicate minerals. Arch of Pathol Lab Med. Submitted for publication. Dunnigan J (1988): Linking chrysotile asbestos with mesothelioma. Am J Ind Med 14:205-209. Kogan FM, Guslnikova NA, Gutevskaya MR (1972): The cancer mortality rate among workers of asbestos industry of the Urals (in Russian). Gig Sanit 37:29-32. Langer AM, Nolan RP, Constantopoulos SH, Moutsopoulos HM (1987): Association of Metsovo lung and pleural mesothelioma with exposure to tremolite-containing whitewash. Lancet 1:965-967. McDonald AD, McDonald JC (1980): Malignant mesothelioma in North America. Cancer 46: 1650-1656. Pooley FD, Mitha R (1986): Fiber types, concentrations and characteristics found in lung tissues of chrysotile-exposed cases and controls. In Fortner JG, Wagner JC, (eds): "Accomplishments in Oncology, The Biological Effects of Chrysotile." Philadelphia: J.B. Lippincott Co. pp. 1-18. Rubino GF, Piolatto G, Newhouse ML, Scansetti G, Aresetti GA, Murray R (1979): Mortality of chrysotile asbestos workers at the Balangero mine, northern Italy. Br J Ind Med 36:187-194. Stanton MF, Layard M, Tegeris A (1981): Relation of particle dimension to carcinogenicity in amphibole asbestoses and other fibrous minerals. JNCI 67:965-975. Stanton MF, Wrench C (1972); Mechanisms of mesothelioma induction with asbestos and fibrous glass. JNCI 48:797-821. Wagner JC (1966): Epidemiology of diffuse mesothelial tumors: Evidence of an association from studies in South Africa and the United Kingdom. Ann NY Acad Sci 132:575-578. Wagner JC (1986): Mesothelioma and mineral fibers. Cancer 10:1905-1911. Wagner JC, Chamberlain M, Brown RC, Berry G, Pooley FD, Davies R, Griffiths DM (1982): Biological effects of tremolite. Br J Cancer 45:352-360. Yazicioglu S, Ilcayto R, Balci K, Sayli BS, Yorulmaz B (1980): Pleural calcification, pleural mesotheliomas, and bronchial cancers caused by tremolite dust. Thorax 1980;35:564-569.