tremolite and Body-Weight

Calidria chrysotile asbestos, which is a serpentine mineral, has been shown to be considerably less biopersistent than the durable amphibole mineral tremolite asbestos, which persists once deposited in the lung. The initial results of this inhalation biopersistence study in rats that demonstrates this difference were reported in Bernstein et al. (2003). This article presents the full results through 1 yr after cessation of the 5-day exposure. This study was based upon the recommendations of the European Commission (EC) Interim Protocol for the Inhalation Biopersistence of synthetic mineral fibers (Bernstein & Riego-Sintes, 1999). In addition, the histopathological response in the lung was evaluated following exposure. In order to quantify the dynamics and rate by which these fibers are removed from the lung, the biopersistence of a sample of commercial-grade chrysotile from the Coalinga mine in New Idria, CA, of the type Calidria RG144 and that of a long-fiber tremolite were studied. For synthetic vitreous fibers, the biopersistence of the fibers longer than 20 microm has been found to be directly related to their potential to cause disease. This study was designed to determine lung clearance (biopersistence) and the histopathological response. As the long fibers have been shown to have the greatest potential for pathogenicity, the aerosol generation technique was designed to maximize the number of long respirable fibers. The chrysotile samples were specifically chosen to have 200 fibers/cm3 longer than 20 microm in length present in the exposure aerosol. These longer fibers were found to be largely composed of multiple shorter fibrils. The tremolite samples were chosen to have 100 fibers/cm3 longer than 20 microm in length present in the exposure aerosol. Calidria chrysotile has been found to be one of the most rapidly cleared mineral fibers from the lung. The fibers longer than 20 microm in length are cleared with a half-time of 7 h. By 2 days postexposure all long fibers have dissolved/disintegrated into shorter pieces. The fibers between 5 and 20 microm in length were cleared with a half-time of 7 days. This length range represents a transition zone between those fibers that can be fully phagocytosed and cleared as particles and the longer fibers that cannot be fully engulfed by the macrophage. The fibers/objects shorter than 5 microm in length were cleared with a half-time of 64 days, which is faster than that reported for insoluble nuisance dusts su

Topics: Animals; Asbestos, Amphibole; Asbestos, Serpentine; Atmosphere Exposure Chambers; Body Weight; Carcinogens; Half-Life; Inhalation Exposure; Lung; Lymph Nodes; Male; Microscopy, Electron, Transmission; Organ Size; Particle Size; Rats

Carcinogenesis bioassays of blocky (nonfibrous) tremolite and amosite asbestos alone or in combination with the intestinal carcinogen 1,2-dimethylhydrazine dihydrochloride (DMH) were conducted with male and female Fischer 344 rats. The minerals were administered at a concentration of 1% in pelleted diet for the entire lifetime of the rats starting with the dams of the test animals. One group of amosite rats also received chrysotile asbestos via gavage during lactation. Group sizes varied from 100 to 250 animals. The offspring from mothers exposed to tremolite or amosite asbestos were smaller at weaning than those from untreated mothers and remained smaller throughout their life. The administration of dimethylhydrazine (DMH) did not affect body weight gain, either in amosite-exposed or nonexposed animals. Survival was comparable in the tremolite and control groups. The amosite-exposed rats showed enhanced survival compared to the untreated controls. DMH exposure reduced survival by approximately one year, although the amosite plus DMH groups survived slightly better than the DMH alone groups. No toxicity or increase in neoplasia was observed in the tremolite-exposed rats compared to the controls. Significant increases (p less than 0.05) in the rates of C-cell carcinomas of the thyroid and monocytic (mononuclear cell) leukemia in male rats were observed in amosite-exposed groups. However, the biological significance of the C-cell carcinomas in relation to amosite asbestos exposure is discounted because of a lack of significance when C-cell adenomas and carcinomas were combined and the positive effect was not observed in the amosite plus preweaning gavage group. The biological significance of an increased incidence of mononuclear cell leukemia is questionable, because of a lack of statistical significance in the amosite group when evaluated using life table analysis, lack of significance when compared to the tremolite control group, and the fact that no toxic or neoplastic lesions were observed in the target organs, i.e., gastrointestinal tract and mesothelium. DMH caused a high rate of (62-74%) of intestinal neoplasia in amosite and nonamosite-exposed groups. Neither an enhanced carcinogenic nor protective effect was demonstrated by exposure to amosite asbestos.

Topics: 1,2-Dimethylhydrazine; Animals; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Body Weight; Cocarcinogenesis; Diet; Dimethylhydrazines; Female; Gastrointestinal Neoplasms; Kidney Neoplasms; Leukemia, Experimental; Liver Neoplasms; Male; Neoplasms, Experimental; Rats; Rats, Inbred F344; Silicic Acid; Silicon Dioxide; Thyroid Neoplasms; Time Factors