International cancer risk assessment: the impact of biologic mechanisms

The use of risk assessment by different governments and agencies varies widely in theory and practice. One major difference is in the consideration given to the biologic mechanisms of cancer causation. U.S. government agencies consider all animal carcinogens to be presumptive human carcinogens and to act in a similar manner without regard to available knowledge on the mechanism of carcinogenicity. Accordingly, standardized models that give linear dose-response at low doses without a threshold are used for predicting human cancer risk from animal studies. Accumulated evidence on biologic mechanisms reveals that some animal carcinogens should not cause cancer in humans at low exposures; other should not at any exposure level. The Netherlands has included such considerations in their cancer classification and risk assessment process. Other governments evaluate each chemical on a case-by-case basis or do not use standardized risk assessment methods for regulatory decisions. To address these issues, the American Health Foundation has convened an International Expert Panel on Carcinogen Risk Assessment.