Chronic effects of dietary exposure to amosite asbestos and tremolite in F344 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.
D019813:1,2-Dimethylhydrazine; D000818:Animals; D001194:Asbestos / Q000008:administration & dosage / Q000633:toxicity*; D017639:Asbestos, Amosite; D017636:Asbestos, Amphibole; D001835:Body Weight; D003043:Cocarcinogenesis; D004032:Diet; D004127:Dimethylhydrazines; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000209:etiology; D007680:Kidney Neoplasms / Q000209:etiology; D007942:Leukemia, Experimental / Q000209:etiology; D008113:Liver Neoplasms / Q000209:etiology; D008297:Male; D009374:Neoplasms, Experimental / Q000209:etiology*; D051381:Rats; D011916:Rats, Inbred F344; D012824:Silicic Acid / Q000008:administration & dosage / Q000633:toxicity*; D012822:Silicon Dioxide / Q000633:toxicity*; D013964:Thyroid Neoplasms / Q000209:etiology; D013997:Time Factors
D017636:Asbestos, Amphibole; D004127:Dimethylhydrazines; D017639:Asbestos, Amosite; D001194:Asbestos; D012824:Silicic Acid; C005846:tremolite; D012822:Silicon Dioxide; D019813:1,2-Dimethylhydrazine