Animal bioassays for carcinogens

Hamm, T. E., Jr. (1994). Design of a long-term animal bioassay for carcinogenicity. In Handbook of Carcinogen Testing, 2nd edition, H. A., Milman, E. K., Weisburger, eds., William Andrew Rublishing, Norwich, NY, pp. 270-285. 

Maronpot, R. R., ed. (1994). Considerations in the Evaluation and Interpretation of Long-Term Animal Bioassays for Carcinogenicity, WilUam Andrew Publishing/Noyes, Norwich, NY. 

Chemicals commonly are screened for carcinogenic potential using two basic types of tests, animal bioassay and in vitro assays. Animal bioassays for carcinogenic activity are most commonly conducted in mammalian species, such as rats, mice, and hamsters. The second type of assay using in vitro procedures screens either for transformation in mammalian cells or for the mutagenic potential of a chemical in a bacterial system after metabolic activation of the test substance (130). Other test systems, such as dominant-lethal mutation tests, translocation tests that screen for chromosomal ab-... 

The NCI (1978) bioassay, which demonstrated carcinogenicity in two species, provides sufficient evidence of carcinogenicity of 1,2-diphenylhydrazine in animals. Biotransformation products of 1,2-diphenylhydrazine include aniline and benzidine, which are known carcinogens in animals (both chemicals) and humans (benzidine) (ERA 1988b,c). Based on the animal evidence for carcinogenicity from the NCI (1978) bioassay and the carcinogenicity of its metabolites,... 

Farrar, D.B. and Crump, K.S. (1988). Exact statistical tests for any carcinogenic effect in animal bioassays. Fundam. Appl. Toxicol. 11 652-663. 

Phenol has been tested in animals for carcinogenicity by the oral and dermal routes, but results are equivocal. In a chronic NCI cancer bioassay (NCI 1980), a significant incidence of tumors (pheochro-mocytomas of the adrenal gland, leukemia, or lymphomas) occurred only in male rats exposed to the lowest dose level (2,500 ppm, 277 mg/kg/day) of phenol but not in male or female mice or male rats exposed to a higher dose level (5,000 ppm, 624 mg/kg/day). Since tumors occurred only in males in one of the two species tested, and since a positive dose-response relationship was not established, this study does not provide sufficient evidence to conclude that phenol is carcinogenic when administered by the oral route. Dermal application of phenol has been shown to result in tumors in mice phenol is a tumor promoter when it is applied after the application of the tumor initiator DMBA (Boutwell and Bosch 1959 Salaman and Glendenning 1957 Wynder and Hoffmann 1961). However, this effect occurs at dose levels of phenol that produce severe skin... 

Evidence from animal bioassays supports the hypothesis that it is the cytosolic system and not the microsomal oxidative system that is responsible for the carcinogenicity of 1,2-dibromoethane. 

In an animal bioassay a dose-related increase in the incidence of adrenal cortical adenomas (with a few carcinomas at this site as well) has been observed in one strain of rats in both sexes. The significance of these lesions in aged rats in unclear. Other bioassays in mice and rats had sufficient limitations, such that the lARC deemed them inadequate for evaluation and concluded that there are insufficient data to evaluate the carcinogenicity of parathion for animals and no data for humans. ... 

For any hazardous substance, estimates of the relationship of dose to response in humans are based on either animal or human data. For example, only about 20 of the approximately 300 chemical carcinogens regulated by EPA have dose-response relationships based on human data from epidemiologic studies the remainder are based on animal bioassays. In contrast, the dose-response relationships for radiation are based primarily on the results of human epidemiologic studies. 

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