Document mqNG4pd07V80Q5JOnNGVarLY0

AMER. INOUST. HYGIENE ASSN. J. 34:277-228 (MAY 1973) w Industrial Hygiene Summary Reports T U i Journal welcomes brief commenti derivad from daily activities which may be useful to other members o f the professfou. Address your communications tot Richard F. Scherberger, Health and Safety Laboratory, Building 320, Kodak Pmfc Works, Eastman Kodak Company, Rochester, New York 14050. Asbestos, Talc and Nitrites in Relation to Gastric Cancer Recently, Merliss1suggested that the high incidence of gastric cancer in Japan may be associated with treatment of rice with talc in Japan. He noted that some commercial "talcs" contain asbestos, which he proposed as an etiologic agent in gastric cancer. Mer liss cited a report of a small excess of gastric cancer in a group of insulation work ers exposed to dusts containing asbestos and a larger excess of pulmonary carcinomas and pleural mesotheliomas in miners who appear to have had mixed exposures to as bestos and talc. He noted that some geo logic deposits of talc are associated with tremolite, anthophyllite and c h ry s o tile varieties of asbestos, accounting for the presence of fibrous particles of-asbestos to gether with platy particles of talc in some commercial preparations of "talc." Our group has carried out tests for car cinogenicity of various preparations of as bestos through experiments with animals. The present paper summarizes some results and reports a new experiment with a prep aration of talc containing asbestos. A pos sible alternative mechanism involving ni trites in gastric carcinogenesis is discussed. In 45 hamsters maintained throughout their lives on diets containing 1% of the chrysotile or amosite varieties of asbestos, we found no gastric carcinomas and no tu- Thii work w, lupportcd by USPHS Rcaearch Grant EC 00224 from National Institute of Occupational Safety and Health, and by a (rant from Fannie E. Rippcl FbuodiUoA mors in the gastrointestinal tract except for a neoplasm in the mesentery of the colon.2 We are unable to relate that lesion to the treatment, since ashing has revealed no as bestos fibers in it. After intrapleural injection of 25 mg chrysotile or amosite into hamsters, we re ported tumors diagnosed as pleural mesothe liomas.2 Eight to 10 such tumors were found in each of 3 groups of 50 hamsters treated at this dose level.3 We have now completed an experiment in which the hamster-intrapleural method was used to test for carcinogenicity of a sample of talc containing asbestos. For this work, we obtained samples of commercial talcs from Whittaker, Clark & Daniels, Inc., New York Gty. A sample of cosmetic talcum powder grade was seen by microscopic ex amination to be composed of platy particles typical of the mineral, talc (hydrous mag nesium silicate). Another sample of a grade used for some industrial purposes (" #13 Talc") was found to be a mixture of platy and fibrous particles. X-ray diffraction analysis revealed the presence of major mounts of tremolite asbestos and talc and a minor amount of a serpentine mineral (antigorite). Each of 50 hamsters were given right intrapleural injection of 25 mg of this sam ple suspended in 0.5 ml saline. The animals were followed for their life spans. No tu mors attributable to the treatment were found. Granulomatous lesions were com- 227 ST03IZ200 PLA IN TIFF'S EXHIBIT W CD -83 DOW 0 4 8 1 1 22t tnon on pleural. surfaces, but these lesions tended to be small and focal in contrast to larger and more fibrotic lesions induced in hamsters by chrysotile or amosite. The negative results of this test for car cinogenicity of a talc containing asbestos, and our earlier test on feeding asbestos to hamsters, do not offer support to the view that asbestos-containing talc contributes to the incidence of gastric cancer in Japan. Although death rates reported for gastric cancer are notably high in Japan in com parison to other countries, the highest re ported rate comes from Chile.4 Studies of gastric cancer in Chile have been reported from our laboratory with an hypothesis that high rates for esophageal and gastric cancer may be due to conversion of nitrates to nitrites by soil bacteria with subsequent synthesis of nitrosamine carcinogens in plants used as food or through interaction in the stomach with secondary amines in food.5 Chile has the world's largest known ge ologic deposits of nitrates, which are used as fertilizers. Nitrosamine has been reported in wheat plants and wheat grains.6 Nitro samines can form through interaction of nitriles with secondary or tertiary amines in tlie stomach, and have been shown to induce esophageal and gastric cancers in rats.7-8 High concentrations of secondary amines have been reported from Japan in dried fish.1' The situation invites attention to a po tential role of the nitrogen cycle in environ mental carcinogenesis. A source for direct ingestion of nitrites by human populations May, 1973 arises from use of nitrites as food additives. Other potential factors in gastric carcino genesis have been recently reviewed by Haenszel et a/.10 who found no support for the talc-asbestos hypothesis on epidemiologic grounds. 1. Merliss, R. R.: Talc-Treated Rice and Japanese Stomach Cancer. Science 173:1141 (Sept 17, 1971). 2. Smith, W. E., L. Miller, R. Elsasser and D. Hubert: Tests for Carcinogenicity o f Asbestos. Ann. S ew York Acad. Science 132:456 (Dec. 31, 1965). 3. Smith, W. E., D . Hubert and M. Badollet: Biologic Differences in Response to Long and Short Asbestos Fibers. Amer. Ind. Hyg. Assoc. J. 33: Abstract #162 (Feb. 1972). 4. Macdonald, E., and P. Wolf: in Epidemiologi cal, Experimental and Clinical Studies on Gastric Cancer. Japanese Cancer Assn. G A N N Monograph 3 (1968). 5. Zaldivar, R.: Geographic Pathology o f Oral, Esophageal, Gastric and Intestinal Cancer in Chile. Ztsch. Krebsforscli. 75:1 (1970). 6. Hedler, L,, and P. Marquardt Ueber das Vorkommen von Nitrosaminen in Nahrungs und F u t t e r m it t e ln . Naunyn-Schmiedebergs Arch. Pharm. exp. Path. 259:176 (1968). 7. Sander, 1-, F. Schweinsberg, and H. Menz: Untersuchungen ueber die Entstehung cancerogener Nitrosamine. im Magen, Hoppe-Seyler's Ztsch. physiol. Chem. 349:1691 (1968). 8. Druckrey, H., S. Ivankovic, and D. Schmaehl: Organotrope carcinogene Wirkungen bei 65 verschiedenen N-nitroso-Verbindungen an BDRatten. Ztsch. Krebsforsch. 69.103 (1967). 9. Kawamura, T., K. Sakai, and F. Miyazawa: Studies on nitrosamines in foods (IV ). Dis tribution o f secondary amines in foods. J. Food Hyg. Soc. (Japan) 12:192 (1971). 10. Haenszel, W., M. Kurihara, M. Segi, and R. Lee: Stomach Cancer among Japanese in Hawaii. J. Nafl Cancer Inst. 49:969 (1972). William E. Smith, MS). Health Research Institute Fairleigh Dickinson University Madison, S J . 07940 ST0312201 DOW 0 4 8 1 2