The relevance of experimental carcinogenicity studies to human safety

The two year rodent bioassay has been the standard for carcinogenicity screening for 5 decades. However, numerous examples exist showing that a positive result is not predictive of human cancer risk because of lack of relevant dose and/or mode of action. Utilizing basic principles of carcinogenesis, evaluating chemicals for DNA reactivity, immunosuppression, estrogenic activity and increased cell proliferation provides a more scientific, rationally based process for evaluating risk, in conjunction with metabolism in human cell systems and dose response considerations. George Box once stated, “Models; all are wrong, some are useful.” The two year rodent bioassay screen for carcinogenesis is no longer useful.