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TII35 RENDIX CORPORATION CORPORATE ENGINEERING STAFF SOUTHFIELD, MICHIGAN HEALTH-HAZARDS OF ASBESTOS A REVIEW OF THE MEDICAL LITERATURE Prepared By: Jacob W. Tawiah / cc / December 11, 1975 HWMR0033666 EXECUTIVE SUMMARY HEALTH-HAZARDS OF ASBESTOS A, CURRENT MEDICAL KNOWLEDGE 1. Nature of Asbestos-Related Diseases Present medical knowledge associates asbestos with three primary diseases: Asbestosis; Bronchogenic (lung) Cancer; and Mesothelioma., a rare form of cancer. All three diseases affect the lungs and in the case of mesothelioma, the abdominal cavity may also be affected. Asbestosis can cause death but it is not always fatal, bronchogenic cancer is fatal and mesothelioma is the most deadly of them all. 2. Is there a safe exposure level? ' There is general agreement that the.risk of developing one of the asbestos-related diseases Is positively correlated with the intensity and duration of exposure to asbestos .dust. ' . However, there is no conclusive proof of a safe threshold level of exposure. If and when such a threshold level is determined.present indications are that it will vary from type of asbestos fiber to type of asbestos fiber; from occupation to occupation; and from disease to disease. 3. What is the relationship between asbestosis and lung cancer? There are reported cases of lung cancer victims showing symptoms of asbestosis, but if an individual does not smoke, asbestosis does not lead to lung cancer. The medical evidence is that asbestosis do occur irrespective of one's smoking habits while an excess risk of lung cancer has thus far been only associated with cigarette smokers. 4.- What are the relative risks following exposure to only one variety of asbestos? . All commercial forms of asbestos cause asbestosis, bronchogenic cancer and mesothelioma. However, the risk is greatest with crocidolite, less with amosite and perhaps, still less with chrysotile/^k) 5. What is. the mechanism of disease causation in asbestos-related diseases? Existing evidence appear to indicate that extracellular processes and the physical features of fibers constitute a major part of the causation of the lung diseases associated with exposure to asbestos dust. The fiber diameter appear to be the controlling factor in the causation of disease. HWMR0033667 The association of "asbestos-caused" cancer with cigarette smoking, . coupled with the physical nature of the process of disease causation, as present studies indicate; perhaps, permits the speculation that asbestos fibers or other fibers of similar physical dimensions, once in the lungs act only as a mechanical confactor in enhancing retention, inhibiting clearance and modifying the distribution of inhaled insol uble cigarette smoke particles which are proven to be carcinogenic. It may be inferred, therefore, that other insoluble particulate matter of similar physical dimensions, as asbestos may be equally cocarcino- genic as asbestos. 6. What other causes of mesothelioma are there? There have been reported cases of mesothelioma that cannot be linked to asbestos but there are no known other cuases of the disease other than exposure to asbestos dust. 7. Can asbestos cause other diseases? Yes. There is ample evidence of an association between pleural plaques and.all types of exposure to asbestos, and to all types of asbestos fiber. Asbestos is not the only cause of plaques but it is the most common. (33) 8. Is it possible to detect' asbestosis early enough to permit a cure? With regular x-ray examinations it is possible to detect the onset of . asbestosis to at least permit its control. However, the latent period of asbestos-related diseases is estimated to be about 20 years.. COMMENTARY There is no doubt that the inhalation of substantial amounts of asbestos can lead to increased rates of various types of lung disease,, including two forms of cancer. The medical literature is full of solid evidence linking asbestos to disease. Eliminating the emission of asbestos dust into the working environment appears to be an obvious way of dealing with the problem. This, however, may not be the most feasible approach in light of economic consider ations. It then becomes necessary to examine what other alternatives exist. There is strong evidence to indicate that all the diseases associated with asbestos is exacerbated by cigarette smoking. In fact, the evidence is that there is no excess risk of bronchogenic cancer in asbestos workers who do not smoke. In this case it appears that' asbestos is merely a catalyst to the causation, of bronchogenic cancer and the primary carcinogen is cigarette smoke. Ah alternative solution, to the problem that perhaps would be economically attractive to all concerned may thus be. a requirement that workers in the asbestos industry be non-smokers. This option becomes even more attractive when recognition is taken of the fact that existing evidence, even though inconclusive at this time, indicates that other fibers with certain physical, dimensions (below 3 yx. m diameter) irrespective of chemical composition may have the same effect as asbestos. ' HWMR0033668 3 In the self interest of Bendix the apparently physical nature of the mechanism of disease causation of asbestos fibers should be.carefully considered in our search for alternate material for our brake lining composition. P.S: SEE ATTACHMENT A FOR SUPPORTING DETAIL AND BIBLIOGRAPHY OF THE MEDICAL LITERATURE REVIEWED. ' HWMR0033669 ATTACHMENT A HEALTH-HAZARDS OF ASBESTOS A REVIEW OF THE MEDICAL LITERATURE ASBESTOS-RELATED DISEASES . . Three primary diseases are known to be caused or induced by the exposure to and inhalation of asbestos fibers in industrial environments.. They are; asbestosis; bronchogenic (lung) cancer; and mesothelioma, an extremely rare form of cancer which affects the lining of the pleural (lung) cavity or the peritoneal (abdominal) cavity. . - Asbestosis . This is. the most common of the three asbestos-related diseases. It is one of the lung diseases classified as "pneumoconioses.'" Among others . arc cil.icocic, from crystalline cilice duct; byccinocie from cotton dust, talcosis from talc; and anthracosis from coal dust. Asbestosis is a non-malignant fribotlc. lung condition which shows a high frequency of occurrence in populations exposed to asbestos dust, if the dust con centration ' is high or the duration of exposure is long, When an asbestos fiber is inhaled into the body and it. is not captured and eliminated by the normal cleansing mechanisms, two different actions can occur. It can be encapsulated with iron-rich protein - in which case it is then referred to' as an "asbestos body" or "ferruginous body." Or, it can remain in a naked- state-uncoated. For all ;intents and purposes, the asbestos fiber if coated is harmless. On the other hand, If the fiber remains in a naked state in the lung, then an almost uncontrolled growth of cells may begin, resulting in the formation of collagen, or scar tissue. When collagen forms in the lungs, it alters the normal tissue so that it no longer functions properly. When, this biological reaction occurs, the body's vital capacity is greatly reduced and the oxygen-carbon dioxide exchange function within ' the lungs is altered. The overall effect is poor ventilation and labored breathing, which are signs of asbestosis. Other physical symptoms of asbestosis are rales - unusual sounds produced in the chest cavity, and finger clubbing. (^a) Asbestosis has been shown in numer^jis studies to cause death but it is not necessarily always fatal. ^ ' All the commercially significant varieties of asbestos; chrysotile, amosite, croeidolite and anthophyllite, have been shown to cause asbestosis. (^"9) However, there is considerable evidence to suggest that the risk is greatest with croeidolite, less with amosite and perhaps still less with chrysotile.(10a,b, 11, 12) . ' While exact dose-response relationships are not well established, there is general agreement that there exists.a positive correlation between intensity of exposure and the frequency of occurrence of asbestosis. HWMR0033670 2- - Studies indicate that pulmonary fibrosis is augmented in asbestos workers by cigarette smoking. (-^) xt has also been shown that the risk of death from asbestosis may be increased by cigarette smoking. (14) Bronchogenic (lung) Cancer: . A high frequency of bronchogenic cancer greater than that expected on the basis of the general male population has been shown to be manifested among persons who have had exposure to asbestos in indus trial settings. (15-18) studies (19-25) have shown that all types of asbestos can give rise to an excess of bronchogenic cancer under some circumstances. It has been forcefully demonstrated that the risk of bronchogenic cancer is greatest with crocidolite, less with amosite and perhaps, still less with chrysotile. Evidence from studies using dust exposure assessments has' generally shown that the excess risk of bronchogenic cancer is related to dose and duration of exposure. Perhaps the most significant conditional factor asso ciated with the excess risk of bronchogenic cancer related to indus trial exposure to asbestos is the requirement of cigarette.smoking. Existing evidence indicates that non-smokers do not show any excess risk of bronchogenic cancer regardless of their exposure to asbestos. (26, 27). ' The biological mechanisms involved in the development of bronchogenic cancer and mesothelioma are not .yet clearly established. However, evidence based on studies thus far conducted on this subject permits reasonable speculation on a probable course of events. . In a study, conducted by M. F. Stanton (^^) of the Laboratory of Pathology, National Center Institute, Bethesda, U.S.A., various structural forms of asbestos, fibrous glass and aluminum oxide were tested for carcinogenicity on the pleura (lung) of rats. .Results ' from all three materials indicate- that carcinogenicity is related primarily to fibrous structure rather than to physicochemical pro perties. A comparison of the dimensional distribution of fibers in those samples of asbestos and glass producing high and low tumor Incidence indicate that carcinogenicity may be related to fibers below 2.5 m (micron) in diameter and between 10 to 80.yYin in length. . Another study by V. Tirabrell ('^of he mrc Pneumoconiosis Unit, Llandough Hospital, Penarth, UK. concluded that "extracellular processes and the physical features of . fibers appear to constitute a major part.of the etiology (causation) of the lung diseases associated with exposure to asbestos dust, including the cancers. -The biological exposures which different types of asbestos fibers produce when inhaled seem to be governed largely by the aerodynamic properties of the fibers. The physical characteristics of the fibers which form the basis of these suggested expla nations are fiber diameter, fiber length and fiber morpho logy, the central parameter being fiber diameter." . . HWMR0033671 3- Further evidence supporting the thesis of physical processes as etiological (causation) mechanisms of asbestos-related cancers is provided by Dr. Edward A, Martell of the National Center for Atmos pheric Research. In two articles (30,31) published in 1974 and 1975, Dr. Kartell asserted and provided evidence to support the following: .' . ''Airborne 210 Pb is concentrated on small Aitken particles which.accumulate on tobacco trichomes. Tobacco curing and the combustion of trichomes in burning cigarettes produce insoluble particles of high 210pb radioactivity . which.are inhaled and deposited in the bronchi of smokers. The subsequent ingrowth of 210po results in high local alpha irradiation which may account for bronchial cancer among smokers." . The significance of this finding is that coupled with the cited evi dence of the physical nature of the causation of asbestos-related cancers, and other related facts, the suspected carcinogenicity of asbestos (or fibers of an appropriate physical dimensions) may be subject to reinterpretation. It has been observed by Selikoff et al (26,27) that bronchial carcinoma deaths among asbestos workers who smoke cigarettes are about eight times that expected for cigarette smokers in general, whereas there were no excess bronchial carcinomas among asbestos workers who did not smoke. It thus follows that asbestos is not a primary carcinogen. It is indeed a cocarcinogen. . .. It may be concluded, therefore, that it is likely that an accumulation of the small asbestos fibers (or other similar fibers) in the lungs of the workers acts only as a mechanical cofactor in enhancing retention, inhibiting clearance, and modifying the distribution of inhaled insoluble alpha-emitting radioactive particles from cigarette smoke which are proven to be carcinogenic. Mesothelioma Mesothelioma is the third asbestos-related disease. It is an extremely rare form of cancer which affects the lining of the lung cavity and of the abdominal cavity. Mesothelioma is by far the most serious of the three diseases because at the present time, once it is diagnosed, it is inevitably fatal -- there is no known treatment. Death usually occurs within 18 months after diagnosis. Although there are reported cases of mesothelioma that can not be linked to asbestos, asbestos remains the prime suspect as the carcinogenic agent. HWMR0033672 . -4- According to P. C. Elmes , the tumor usually starts In the pleura (lung), but a small proportion starts in the peritoneum (abdomen). In either case, pain is usually the first symptom, followed later by breathlessness and loss of weight. The time course of the disease is short, "averaging.13-14 months for the pleural cases and six months for the peritoneal." Even though the evidence (2^) is not conclusive, it appears that cigarette smoking aggravates the occurence of mesothelioma. The causation of this disease in so far as it relates to the role of asbestos, is similar to bronchial cancers as previously described. HWMR0033673 REFERENCES 1. Merewether, E.R.A., and Price, C.W. "Report on Effects of Asbestos Dust on the Lungs and Dust Suppression in the Asbestos Industry." Her Majesty's Stationary Office, London, 1930. 2. Sayers, R.R., and Dreesen, W.C. "Asbestosis." American Journal of Public Health, 29, 205; 1939. ' 3a. Johns-Manville Corporation, "Asbestos and Health" Environmental Facts/ Asbestos, March 1974. 3b. Selikoff, I.J., Churg, J., and Hammond, E.C., "The Occurrence of Asbestosis Among Insulation Workers in the United States," Ann. N.Y. Acad. Sci. 132, 139; 1965. . (4 through 9 were .presented at IARC Conference on Biological Effects of Asbestos, Lyon, France, 1972) 4. McDonald,. J.D., "Asbestosis in Chrysotile Mines and Mills" 5. Sluis-Cremer, G.K., and duToit, R.S.J., "Amosite and Crocidolite Mining and Milling as Causes of Asbestosis." 6. Ahlman, K, et al; "Anthophyllite Mining and Milling as a Cause of Asbestosis." 7. Smifixer, W.J., and Lewinsohn, H.C., "Asbestosis in Textile Manufacturing." 8. Cooper, W.C., and Miedema, J., "Asbestosis in the Manufacture of Insulating Materials." ' 9,. Enterline, P.E., and Weill, H., "Asbestosis in Asbestos Cement Workers." 10a. Timbrell, V., "The Inhalation of Fibers." Proceedings of the International Conference on Pneumoconiosis, D.ept, of Mines, Republic of South Africa, 1969. . 10b. Report of the Advisory Committee on Asbestos Cancers.to the Director of the International Agency for Research on Cancer, October 6, 1972. 11. Wagner, J.C., and Skidmore, J.W., "Asbestos Dust Deposition and Retention in Rats." Ann. N.Y. Acad, Sci., 132, 77, 1965. 12. Wagner, J.C, "Asbestosis in Experimental Animals," British Journal of Industrial Medicine, 20, 1, 1963. 13., Weiss, W., "Cigarette Smoking, Asbestosis and Pulmonary Fibrosis." Amer. Rev. of Respiratory Diseases, 104, 223-227, 1971. HWMR0033674 REFERENCES PAGE 2 14. Auerbach, 0. et al; "Smoking Habits and Age in Relation to Pulmonary Changes; Rupture of Aveolar Sep turns, Fibrosis, and Thickening-of Walls of Small Arteries and Arterioles." New England Journal of Medicine 269, 1045-1054, 1963. 15. Doll, R., "Mortality from Lung Cancer in Asbestos Workers." British Journal Industrial Medicine 12, 81, 1955. 16. Selikoff, I.J., J.. Churg, and E. C. Hammond, "Asbestos Exposure and Neoplasia." J. Am. Med. Assoc, 188; 22-, 1964, . 17. Elmes, P.C. and J.J.C. Simpson, "Insulation Workers in Belfast - Mortality . 1940-66" Brith. J. Ind. Med. 28, 226-236, 1971. 18. Newhouse, M.L., "A Study of the Mortality of Workers in Asbestos Factory." Briti J. Ind. Med. 26, 294-301, 1969. (19 through 26, 28, 29, 32, and 33 were presented, at IARC Conference on Biological Effects of Asbestos, Lyon, France, 1972) 19. McDonald, J.C., "Cancer in Chrysotile Mines and Mills." 20. Webster, I., "Malignancy in Relation to Crocidolite and Amosite." 21. Meurman, L.O. et. al., "Mortality and Morbidity of Employees of Authophyllite Asbestos Mines in Finland." 22. Newhouse, M.L., "Cancer Among'Workers in the Asbestos Textile Industry." , 2.3. Selikoff, I.J., et al; "Cancer Risk of Insulation Workers in the United States." 24. Bohlig, H. and Hain, E., "Cancer in Relation to Environmental Exposure." 25. Pooley^, F.D. "Mesothelioma in Relation to Exposure." 26. . Selikoff, I.J. and fi.C. Hammond, "Relation of Cigarette Smoking to Risk of Death of Asbestos-Related Disease Among Insulation Workers in the United States." 27. Selikoff, I.J,, E.C. Hammond, and J. Churg, "Asbestos Exposure, Smoking and .Neoplasia." Journal of Amcr. Med. Assoc. 204, 106-112, 1968. 28. Stanton, M.F., "Some Etiological Considerations of Fiber Carcinogenesis." 29. Timbrell, V., "Physical Factors as Etiological Mechanisms." HWMR0033675 REFERENCES PAGE 3 30-. Kartell, E.A., ''Radioactivity of Tobacco Trichomes and. Insoluble Cigarette Smoke Particles/' Nature, 249, 5454, 215-217, May 17, 19744 31. Martell, E.A., ''Tobacco Radioactivity and Cancer in Smokers," American Scientist, 63, 404-412, July-August 1975. 32. Elmes, P.C., "The Natural History of Diffuse Mesothelioma." 33. Jones, J.S.P. and G. Sheers, "Pleural Plaques." HWMR0033676