NTP Lifetime Carcinogenesis Studies of Chrysotile Asbestos (CAS No. 12001-29-5) in Syrian Golden Hamsters (Feed Studies)

Abstract

NTP Carcinogenesis studies of short range (SR), intermediate range (IR), or intermediate range chrysotile asbestos in combination with the intestinal carcinogen 1,2-dimethylhydrazine dihydrochloride (DMH) were conducted with male and female Syrian golden hamsters. Both forms of chrysotile asbestos were administered at the concentration of 1% in pelleted diet for the entire lifetime of the hamsters starting with mothers of the test animals. Group sizes varied from 125 to 253. Starting at 6 weeks of age, male and female hamsters in the intermediate range chrysotile/DMH study were given oral doses of DMH (4 mg/kg) every other week for a total of 5 doses. There was no adverse effect on body weight gain or survival by either form of asbestos or by asbestos in combination with DMH. A significant increase (P< 0.05) in adrenal cortical adenomas was observed in male hamsters exposed to SR and IR chrysotile asbestos and in females treated with IR chrysotile asbestos when compared to the pooled control groups (males: pooled controls, 25/466, 5%; SR chrysotile, 26/299, 11%; IR chrysotile, 24/244, 10%; females: pooled controls, 15/468, 3%; IR chrysotile, 18/234, 8%). However, statistical significance was lost when these dosed groups were compared with concurrent control groups (males: SR control, 7/115, 6%; IR control, 7/115, 6%; females: SR control, 4/112, 4%; IR control, 6/118, 5%). The results of the combination study (IR chrysotile plus DMH) did not yield a significant increase in tumors above the background level observed in the DMH group alone or in the untreated control group. The DMH failed to yield a background level of intestinal tumors high enough to provide a valid test of the cocarcinogenic potential of chrysotile asbestos. For this reason, the cocarcinogenic potential of orally administered asbestos should be considered untested. Under the conditions of these studies, neither short range chrysotile nor intermediate range chrysotile asbestos was carcinogenic when ingested at 1% levels in the diet by male and female Syrian golden hamsters. While there were increases in the rates of adrenal cortical adenomas in male and female hamsters exposed to intermediate range chrysotile asbestos compared to the pooled groups, these incidence rates were not different when compared with the concurrent control groups. Additionally, the biologic importance of adrenal tumors in the absence of target organ (gastrointestinal tract) neoplasia is questionable. The coNTP Carcinogenesis studies using IR chrysotile asbestos and 1,2-dimethylhydrazine dihydrochloride were considered inadequate because there was no increase in intestinal neoplasia in the DMH group. Levels of Evidence of Carcinogenicity: Intermediate Range: Male Hamsters: Negative Female Hamsters: Negative Intermediate Range + dimethyl hydrazine: Male Hamsters: Inadequate Female Hamsters: Inadequate Short Range: Male Hamsters: Negative Female Hamsters: Negative.