asbestos--amosite and Carcinoma

This article describes the activity of an E-glass microfiber (104E) during chronic inhalation and intraperitoneal injection studies in rats. Results are compared with another microfiber of similar dissolution rate (k(dis)), code 100/475, and the more durable amosite asbestos, both of which we had previously used in similar experiments (Davis et al., 1996). Rats were exposed to aerosol concentrations of 1000 fibers (longer than 5 microm)/ml, as measured by optical microscopy, for 7 h/day, 5 days/wk. Subgroups of rats were followed for mean lung burden, early and late signs of fibrosis, and tumor incidence. At the end of 12 mo of exposure, the mean number of 104E fibers of all lengths in the lungs was approximately double that for amosite but two-thirds of that for 100/475. For fibers longer than 15 microm, the mean 104E burden was similar to that for the amosite and more than twice that of the 100/475. After a 12-mo recovery period, the retained lung burdens (of fibers of all lengths) were approximately 30% of those at 12 mo for both microfibers, and somewhat higher (approximately 44%) for amosite. Amosite and 100/475 fibers longer than 15 microm were more persistent in the lungs than 104E fibers. The chemical composition of 104E fibers did not appear to have been significantly altered by up to 24 mo of residence in lung tissue, whereas the composition of 100/475 was substantially altered over the same time period. From the inhalation study, out of the pathology subgroup of 43 animals exposed to 104E microfibers, 10 had lung tumors (7 carcinoma, 3 adenoma) and 2 had mesotheliomas, whereas in 42 rats exposed to amosite asbestos, there were 16 lung tumors (7 carcinoma, 9 adenoma) and 2 mesotheliomas. The 104E- and amosite-treated animals had similar levels of fibrosis. In contrast, 38 animals treated with 100/475 had little fibrosis, 4 lung tumors (adenomas), and no mesotheliomas. The greater pathogenicity of the 104E fibers, compared to 100/475 fibers, might be partly explained by the greater numbers of long fibers retained in the lung after 12 mo of inhalation. However, we speculate that modification of surface properties by extensive selective leaching of some glass components reduces the toxic potential of 100/475. In a parallel intraperitoneal injection study, 104E caused considerably more mesotheliomas (21 rats out of 24) than 100/475 (8 rats out of 24). In addition, 104E appeared to be more active than amosite asbestos, since mesotheliomas appeared mu

Topics: Administration, Inhalation; Aerosols; Animals; Asbestos, Amosite; Body Burden; Carcinoma; Glass; Inhalation Exposure; Injections, Intraperitoneal; Lung; Lung Neoplasms; Male; Mesothelioma; Mineral Fibers; Neoplasms, Experimental; Particle Size; Pulmonary Fibrosis; Rats; Rats, Wistar; Survival Analysis; Survival Rate; Toxicity Tests

To clarify co-carcinogenic effects of chrysotile (Chry) and amosite (Amo) asbestos with benzo(a)pyrene (Bap), 0.2 mg UICC (International Union against Cancer) standard reference sample of asbestos and 0.4 mg Bap were applied intratracheally once a week for 6 weeks. Eighteen and 24 months after the last instillation the number of tumors was examined. The Chry + Bap group yielded 37 tumors including 16 carcinomas in 12 animals, and the Amo + Bap group yielded 30 tumors including 11 carcinomas in 12 animals. Tumor-bearing animals were 100% in the Chry + Bap group and 92% in the Amo + Bap group, and carcinoma-bearing animals were 83% and 67%, respectively. The animals injected with Chry, Amo, and Bap alone developed no tumors. The number of tumors and carcinomas and the frequency of the tumor- or carcinoma-bearing animals in Chry + Bap and Amo + Bap were significantly higher than those of the groups injected independently. The number of tumors or the frequency of tumor-bearing animals was higher in Chry + Bap than in Amo + Bap; however, these differences were not significant. These results indicate that both Chry and Amo play an important role in the genesis of bronchogenic carcinoma.

Topics: Adenoma; Animals; Asbestos; Asbestos, Amosite; Asbestos, Serpentine; Benzo(a)pyrene; Carcinogenicity Tests; Carcinoma; Cocarcinogenesis; Cricetinae; Lung Neoplasms; Mesocricetus

We have previously shown that there are differences in the sizes of fibers of amosite asbestos in different parts of the lung in workers with relatively high asbestos exposure and malignant pleural mesothelioma. To determine whether this distribution pattern is specific to cases of mesothelioma, we compared the fiber distribution in the lungs of 20 cases of mesothelioma and 10 cases of carcinoma of the lung. The two test groups were statistically identical in terms of age, and exposure period, and overall both groups had very similar mean fiber concentrations and mean fiber sizes. When individual sampling sites within the lung were considered, neither group showed preferential fiber concentration in any area. However, there were definite differences in the intrapulmonary fiber size distribution both within and between the two groups: Cases of mesothelioma showed accumulation of lung fibers in the peripheral upper lobe with shorter central upper lobe fibers. The lung cancer cases demonstrated a reverse pattern, with shorter fibers in the peripheral compared to central upper lobe, but accumulations of long fibers in the peripheral lower lobe. Fiber surfaces and masses showed similar differences among sample sites. We conclude that (1) there is no evidence for fiber concentration variations in different portions of the lung; (2) there is strong evidence for variations in fiber sizes in different portions of the lung, and these differences are most clearly related to fiber length, surface area, and mass; (3) contrary to data from experimental animals, there are no clear gravitational effects on fiber distribution in humans; and (4) there are reproducible differences in intrapulmonary fiber size distribution between mesothelioma and lung cancer cases. These differences may be a manifestation of individual handling of mineral particles because of structural variations in individual lungs.

Topics: Aged; Asbestos; Asbestos, Amosite; Carcinoma; Humans; Lung Neoplasms; Mesothelioma; Middle Aged; Smoking; Tissue Distribution