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 obtai...

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Bibliographic Details
Published in:Carcinogenesis (New York) 1988-11, Vol.9 (11), p.2045-2052
Main Authors: Hoel, David G., Haseman, Joseph K., Hogan, Michael D., Huff, James, McConnell, Ernest E.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Carcinogens - classification
Carcinogens - toxicity
Chemical agents
Dose-Response Relationship, Drug
Hyperplasia
Liver - drug effects
Liver - pathology
Medical sciences
Mutagenicity Tests
Mutation - drug effects
Neoplasms, Experimental - chemically induced
Precancerous Conditions - chemically induced
Precancerous Conditions - pathology
Risk Factors
Sex Factors
Tumors
Citations: Items that cite this one
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Summary: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.
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/9.11.2045