Use of rodent carcinogenicity test results for determining potential cancer risk to humans.
A high proportion of "human" and "probable human" carcinogens as categorized by the International Agency for Research on Cancer have been identified through observations in workers. The excess cancer risk has often been quite high. Most substances known to cause cancer in humans are now known to cause cancer in animals. In the past two decades, an increasing number of substances first shown to cause cancer in animals are now known to cause or are highly suspected of causing cancer in humans (and quite often in workers). The observations necessitate the use of rodent cancer test results for identifying and regulating potential environmental carcinogens. The role of cell proliferation (CP) in the carcinogenic response is important from a regulatory view in terms of both qualitative and quantitative evidence. If CP influences the carcinogenic response, the use of such data to modify dose response in the low-dose range is another factor that needs to be considered. Presentations at this symposium, however, indicate that CP data at the present time should not be incorporated into cancer risk assessments. More simple concepts that affect quantitative dose response and that may result in an artificially low estimated risk but could be adjusted for in the bioassay protocol have usually been ignored. A balanced approach would be to incorporate all known factors that influence quantitative estimates of cancer risk when conducting animal cancer bioassays and extrapolating those results to humans.
Health Standards Program, Occupational Safety & Health Administration, Washington, DC 20210.
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D000826:Animal Testing Alternatives; D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000209:etiology*; D009784:Occupational Diseases / Q000209:etiology; D012307:Risk Factors; D012377:Rodentia; D013045:Species Specificity
D002273:Carcinogens