Document DGerVK23jm5Dbe1RnL9m2pm3M

</ j49-r . METALS DIVISION to (Name) Division Location Mr. Or. Df J. L. Myers - Niagara K. S. Lane - NYO F. J* ShOTtSlGGVG " NYO Copy to Messrs. T. W. Carmody R. F. X. Fusaro E. W. Kantz/R. G. Beverly File oate January 11, 1979 Originating Dept. "Cdl1dfl3" AsbGStOS Answering letter date Time of Recognition of Asbestos-Related Cancer The attached is for your information. Extensive documentation upon which this study is based is available through the AIA/NA. t /rmm attachment X4 Harrison B. Rhodes Editorial Asbestos and Cancer: The International Lag1 Bv the early 1940s, ihe question of whether asbes tos caused lung cancer seemed to have been set tled. Asbestosis, the fibrotic changes in the lung resulting from the inhalation of asbestos fibers, bad been recognized for more than 40 years. In 1934 in England. Wood and Gloyne (1) reported 2 cases of lung carcinoma seen at autopsy in 43 cases of asbestosis. and in 1935 Gloyne (2) gave a complete description of these 2 cases. Also in 1935. Lynch and Smith (3) reported one case of lung cancer in an asbestosis case in the United States, and in 1936. Egbert and Geiger (4) re ported a case--also from the United States. In Germany. Nordmann added 2 cases of lung can cer in 2 cases of asbestosis, thus making a total of 6. and concluded. "A cause-effect correlation must be present here, even if I had been the only observer. We arc indeed facing an occupational cancer which affects asbestos workers" (5). Ger man investigators quickly accepted N'ordmann's \ iews (6--8). They were reinforced by an ani mal study in which Nordmann and Sorgc report ed pulmonary carcinomas in 2 white mice as the tenth of asbestos dust inhalation (9). Other Ger man researchers considered this the experimen tal evidence needed for proof and gave Nord mann credit for discovering the relationship be tween asbestos and lung cancer (10, 11). Mean while. in the United States. Hueper declared that, "Asbestosis cancer of the lung is the most re cent newcomer among the occupational cancers >1 this organ" (12). In 1950, West Germany class ified cancer of the lung, when associated with asbestosis (of any degree), an occupational dis ease. And yet, in the LInited States the question of asbestos and lung cancer was debated for another 20 years. What prolonged the debate and pre vented earlier acceptance of a relationship? 1 Based on an unpublished manuscript: Asbestos and Cancer. The First Thirty Years. First, Gloyne. to whom credit for the discovery should really have been given, was extremely cautious in interpreting his findings. In his re port of 1935, Gloyne quoted Bridge and Henry (13) on conditions that must be fulfilled in or der that cancer be classified as industrial in ori gin: (?) the incidence in the occupation under review should exceed significantly that in the general population, and (2) in the occupation concerned, there should be sufficient association of the workers with a substance proved experi mentally to have carcinogenic properties. In Gloyne's lifetime, these conditions were not fulfilled. Nearly all of the evidence dealt with the association of asbestosis and cancer as seen at autopsy. In a paper published posthumously in 1951, Gloyne expressed concern for the selection obviously at work in picking cases for autopsy, [jointing out that necropsy records at the Lon don Chest Hospital showed 21.3 per cent primarylung cancer, whereas in the. general population, only 2.4 per cent of deaths from all causes among persons 15 years of age and more were due to malignant disease of the lung. Lynch, who actually received credit in the end, was no less skeptical. He was concerned not only with the problem of selection, but also with the lack of experimental evidence (14-19). Only Nordmann and Sorge claimed to have pro duced cancer experimentally with asbestos, whereas experiments by Vorwald and Karr (20), King and associates (21). Vorwald and co-work ers (22). Behrens (23). and Hueper (24) had negative results. Moreover. W. E. Smith (25). in a rev iew of work with asbestos and animals, con cluded that the study by Nordmann and Sorge appeared to demonstrate that asbestos did not provoke lung tumors, because of the 2 tumors re ported in animals exposed to asbestos, one was, on the basis of photographs presented, merely a squamous-cell metaplasia, whereas the other, as serted to be an adenocarcinoma, "is a type of tu- \MFRICAN REVIEW OF RESPIRATORY DISEASE. VOLUME 118. 1978 975 A 20 25 : 976 EDITORIAL mor that can arise spontaneously from the mouse door for contributions by hiostatisticians and adenoma." Even Hueper seemed to agree with epidemiologists. It probably also set back accept this, and outside o Germany, Smith's views on ance of a relationship between asbestos and can N'ordmann's work gained some acceptance (19, cer in the United States by another decade. 26,27). The epidemiologists demanded epidemiologic Another problem in the United States was the evidence. In 1956. for example. Hammond and attitude of leaders in the held of pneumoconio Machte (42) stated that with regard to a relation sis--particularly Vorwald, Lanra. and Gardner ship between asbestos and lung cancer "... there (20. 22. 28-32). Their expressed concern was are at present too few cases and too little epi the lack of experimental data. In addition, the demiologic data to establish a significant rela possibility of a different relationship between tionship." In 1958. the Committee on Occupa asbestosis and lung cancer as compared to that tional Cancer of the AMA Council on Occupa between silicosis and lung cancer must have been tional Health concluded that individual case re disturbing. Lanra was also concerned-about the ports contribute little to an understanding of English claims of an association in autopsied occupational cancers and that "specific increases cases of asbestosis. and he wondered how many in.age, sex, and site-specific cancer incidence cases of lung cancer would be found if lungs above normal incidences for the same age. sex, from any sort of population were subjected to and site represent the only reliable evidence for the same minute scrutiny (29). the existence of an occupational cancer hazard" The situation could have been resolved, from (43). the American point of view, by a report by Mere- The first 2 epidemiologic studies of this kind wether (33) who. in 1949, compared lung or of workers exposed to asbestos in North Ameri pleural cancer in cases of ashestosis reported for ca in 1958 and 1960 did not show a significant compensation with lung or pleural cancer in ca increase in lung cancer (44. 45). Thus, as re ses of silicosis. This svas clearly the most impor cently as 1961, it could be said that "there is no tant single study in bringing about a consensus epidemiological evidence [of an association be in Great Britain. In America, however, this seems tween asbestos and lung cancer] among Ameri to have given birth to a new idea: that there was can workers" (46). a relationship between asbestosis and cancer in So what ended the debate in the United States? England and Germany, but not in the United Probably 3 things: (/) positive results of epi States. This idea apparently originated with W. demiologic studies in the United States in 1963 E. Smith: however, another Smith (K. W.) en and 1964, (2) a widely read study of 1960 that larged on this, stating that there svas a difference showed that asbestos was associated with a rare due to the ts pe of fiber used in England and Ger tumor, malignant mesothelioma, and (4) exper many as compared to that used in the United imental evidence in 1962 and 1964 that asbes States (34. 35). Italian writers picked this up as tos had carcinogenic properties (47-51). Thus, an argument for a difference betsveen Italy and the kind of evidence demanded by Bridge and England (36. 37). The argument was also re Henry, and which would have satisfied Gloyne, peated by Eckhardt (38), Gilson (39), and John was finally developed 30 years after Gloyne made stone and Miller (40). his initial observations, and more than 2 decades There svas no anssver to the question of fiber after the acceptance of a relationship between type (or fiber contamination), and it no doubt asbestos and lung cancer in Germany. delayed acceptance by those who were uncer Clearly, the matter involved a question of what tain as to whether a problem truly existed in the is acceptable and conclusive evidence. Perhaps United States. There was, however, an answer special rules are needed for relationships such to the question of selection that so bothered as that between asbestos and lung cancer where Glovne and Lynch. In 1955, an epidemiologic some other biologic response, such as asbestosis, study svas reported of the type envisioned by Bridge and Henry in which it was shown that the incidence of lung cancer in a group of workers exposed to asbestos in England greatly exceeded that in a comparable group in the general popu lation (41). This marked an end to a period when conclusions were based largely on patho logic and clinical observations, and opened the can be used as evidence of significant exposure, and the rules proposed by Bridge and Henry were not appropriate after all. Many investiga tors were convinced of a relationship long before epidemiologic and experimental evidence was available. Aside from the high incidence of lung cancer in patients with asbestosis. they were im pressed by the predominance of cancer in the EDITORIAL 977 lower lobei, the time lapse between exposure and disease, the high incidence in women, and the young age of many of the patients seen. More over, there were reasonable theories concerning mechanisms'by which asbestos could cause can cer. In any event, the issue .was definitely settled for the United States at a conference on the biologic effects of asbestos held in New York. Cityin 196-1 (52). At that conference, additional epi demiologic evidence was presented, and of 20 papers presented in which an opinion was ex pressed, none dissented from the view that as bestos is a cause of cancer. Philip E. Entexlim Professor of Biostatistics Graduate School of Public Health University of Pittsburgh Pittsburgh, Pa. References 1. Wood, W. B., and C.loyne, 5. R.: Pulmonary as bestosis: A Review of One Hundred Cases, Lan cet. 1934.2. 1383. 2. Cloyne. 5. R.: Two cases of squamous carcinoma of the lung occurring in asbestosis. Tubercle. 1935.;;. 5. 3. Lynch. K. M.. and Smith. W. A.: Pulmonary asbestosis. III. Carcinoma of the lung in asbestosilicosis. Am J Cancer. 1935. 24. 56. 4. Egbert. D. 5., and Geiger, A. J.: Pulmonary asbestosis and carcinoma: Report of a case with necropsy findings, Am Rev Tuberc. 1936, 34. MS. 5. Nordmann. M.: Der Berufskrebs der Asbestarbeiter. 7. Krebsforsch. 1938, 47. 288. 6. Hornig. F.: Klinische Betrachtungen zur Frage des Berufskiebes der Asbestarbeiter. Z Krebs forsch. 1938. 47. 281. 7. Tcleky, L.: Der berufliche Lungenkrebs. Acta Union Intern Contr Cancer. 1938, 3, 253. 8. Baader. E. W.: Asbestose, Dlsch Med Wochenschr, 1939, 65. 407. 9. Nordmann. M.. and Sorge. A.: Lungenkrebs (lurch Asbestaub im Tienersuch. Z Krebsforsch, 1941.5/.168. 10. Wrgelin, C.: Der bronchial und Lungenkrebs. Schweiz Med Wochenschr. 1942.72.1053. 11. Wcdler, H. W.: Asbestose und Lungenkrebs. Dlsch Med Wochenschr, 1943,69,575. 12. Hueper. W. C.: Cancer in its relation to occupa, tion and environment. Bull Am Soc Control Cancer. 1943, 25, 63. 13. Bridge, J. C., and Henry. S. A.: Industrial Can cers. Report of the International Conference on Cancer, 1928. William Wood and Co.. London and Baltimore, 1928, pp. 258-268. 14. Lynch, K. M.. Mclter. F. A., and Cain. J. R.: Pulmonary Tumors in Mice Exposed to Asbes tos Dust. Arch Ind Health. 1957. /5.207. 15. Lynch, K. M., and Smith, W. A.: Pulmonary asbestosis. V. A report of bronchial carcinoma and epithelial metaplasia. Am J Cancer, 1939, 36,567. 16. Lynch. K. M.. and Cannon. W. M.: Asbestosis. VI. Analysis of forty ntcropsied cases. Dis Chest, 1948.;;,874. 17. Lynch, K. M.: Potential occupational (actors in lung cancer: Asbestos, proceedings of scientific section, annual meeting of the American Cancer Society, Nov. 5. 1953, American Cancer Society, Inc.. Nin- York. 1953. p. 115. 18. Lynch, K. M.. and Pratt-Thomas. H. R,: Car cinoma of the lung in asbestosis. South Med J. 1955.48.565. 19. Lynch. K. M., Mclter, F. A., and Cain. J. R.: Pulmonary tumors in 207 mice exposed to as bestos dust. Arch Ind Health. 1957, IS,207. 20. Vorwald, A. J., and Karr, J. W.: Pneumoconio sis and pulmonary carcinoma. Am J Pathol. 1939, 74,49. 21. King, E. J.. Clegg, J. W., and Rae. V. M.: The effect of asbestos, and of asbestos and aluminum, on the lungs of rabbits. Thorax. 1946, J, 188. 22. Vorwald. A. J.. Durkan. T. M.. and Pratt, P. C.: Experimental studies of asbestosis, AMA Arch Ind Hyg Occup Med, 1951,3,1. 23. Behrens. W.: Cber cxperimentclle Asbestosis, Schweiz Z Pathol, 1951,14. 275. 24. Hueper, W. C.: Experimental studies in metal cancerigenesis. VI. Tissue reactions in rats and rabbits after perenteral introductions of suspen sions of arsenic, beryllium, or asbestos in lano lin. J Natl Cancer Inst, 1955, IS, 113. 25. Smith. W. E.: Lung cancer with'special reference to experimental aspects. Arch Ind Hyg Occup Med. 1952.5.209. 26. A Quest into the Em ironmental Causes of Can cer of the Lung. Public Health Monograph no. 36. Public Health Service Publication no. 152. U.S. Public Health Sen ice. 1955. pp. 35-38. 27. Cardiner, L. U., quoted by Lynch. K. M., MeIier, F. A., and Cain. J. R.: Pulmonary tumors in 207 mice exposed to asbestos dust. Arch Ind Health. 1957.75.207. 28. Lanza, A. ].: Silicosis and Asbestosis, Oxford University Press, London. 1938. p. 238. 29. Lanza, A. J.: Discussion of paper by W. E. Smith: Lung cancer with special reference to experimental aspects. Arch Ind Hyg Occup Med. 1952.5,209. 30. Lanza, A. J.: The Pneumoconioses, Grune and Stratton, New York and London, 1963. pp. 1323. 31. Gardiner. L. U.: The pathology and roentgeno graph manifestations of pneumoconiosis. JAMA, 1940,774,535. 32. Vorwald, A. J.: Personal communication in Is- '1/6 978 EDITORIAL sclbacher. K. J.. Klaus. H.. and Hardy, H.: As- besiosis and bronchogenic carcinoma. Am J Med. 1953,/J, 721. 33. Merewether, E. R. A.:. Annual Report of the Chief Inspector of Factories for the Year 1947, His Majesty's Stationery Office, London, 1949. pp. 79-81. 34. Smith, W. E.: An evaluation of claims for occu pational factors in cancer of the lungs: Inter national Symposium on the Epidemiology of Lung Cancer. Acta Union Intel n Contra Cancer. 1953, 9. 50. 35. Smith. K. W.: Pulmonary disability in asbestos workers. Arch lnd Health, 1953,12.198. 36. Ramhota, G.: Asbestosi e carcinoma pulmonare in uiia filatrice amianto, Med Lav, 1955.' 16, 242. 37. Francis. A., and Moiurca. G.: Asbestosi c carci noma pulmonare. Minerva Medica, 1956. 17 (2). 1950. 38. Eckhardt. R. E.: Industrial Carcinogens. Mod ern Monographs in Industrial Medicine. Crune and Stratton. New York and London, 1959, pp. 4,99-101. 39. Cilson, J. C.: Industrial pulmonary disease, in Modem Trend< in Occupational Health, R. S. K. Shilling, ed., Buiicruorth and Co.. Ltd., London. 1960. pp. 119-120. 10. Johnstone. R. T.. and Miller. S. E.: Occupation al diseases and industiial medicine, in Occupa tional Cancer, W. B. Saunders Co.. Philadelphia and London. I960, pp. 322-338. 41. Doll. R.: Mortality from lung cancer in asbestos workers. Br J lnd Med. 1955. 12.81. 42. Hammond. E. C.. and Machle. W.: Emironraental and occupational factors, in Pulmonary Careinoma. Pathogenesis, Diagnosis and Treatment, E. Mayer and H. C. Maier. ed.. New York Uni versity Press. New York. 1956, p. 50. 43. Occupational cancer. Council on Industrial Health Committee on Occupational Cancer, JAMA. 1958.166,2171. 44. Braun. D. C.. and Truan, T. D.: An epidemio logical study of lung cancer in asbestos miners. Arch lnd Health. 1958.17.634. 45. Dunn, J.' Ei. Linden. G.. and Bredow. L.: Lung cancer mortality experience of men in certain occupations in California, Am J Public Health. 1960, SO (2). 1475. 46. Johnstone, R. T.: Silicosis and cancer [questions and answers], JAMA. 1961. 17J. 353. 47. Mancuso, T. F.. and Coulter. E. J.: Methodology in industrial health studies: The cohort ap proach with special refeience to an asbestos company, Arch Environ Health. 1963.6.210. 48. Selikoff, I. J.. Churg. J.. and Hammond. E. C.: Asbestos exposure and neoplasia, JAMA, 1964, /SS. 22-26. 49. Wagner. J. C.. Slcggs. C. A., and Marchand. P.: Diffuse pleural mesothelioma and asbestos expo sure in North Western Cape Prosince, Br Jlnd Med. 1960.17.260. 50. Wagner. J. C.: Experimental production of mesothelial tumours of the pleura by implantation of dusts in laboratory animals. Nature. 1962, 196, 180. 51. Smith, W. E.. Miller. L., Churg. J.. and Selikoff, I. J.: Pleural reaction and mesothelioma in hamsters injected with asbestos [abstract], Proc Am Assoc Cancer Res. 1964. }. 59. 52. Biological efTccts of asbestos larticle 1). Ann NY Acad Sci. 1965. pp. 1-766.