The impact of toxicity on carcinogenicity studies: implications for risk assessment.
This paper explores the inter-relationship between toxicity, genotoxicity, and carcinogenicity in laboratory rodents. To our knowledge this is the first attempt to integrate these factors and evaluate their implications for the process of risk assessment. The evaluation is based on information obtained from 2-year laboratory-animal studies involving 99 chemicals. The data suggest that only seven of the 53 positive carcinogenicity studies exhibited the types of target organ toxicity that could have been the cause of all observed carcinogenic effects. Furthermore, no apparent difference in mutagenicity as measured by the Ames Salmonella assay was observed between 'high dose only' carcinogens and the entire set of carcinogens. These findings suggest that the number of chemical carcinogens that we can identify solely through rodent studies as being potential tumor inducers through some indirect mechanism is small. Generally speaking, the identification of histopathological effects is not sufficient in itself for justifying mechanistic assumptions, and supplemental biological information will be necessary to reach definitive conclusions.
D000818:Animals; D002273:Carcinogens / Q000145:classification* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006965:Hyperplasia; D008099:Liver / Q000187:drug effects / Q000473:pathology; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology; D012307:Risk Factors; D012737:Sex Factors
D002273:Carcinogens