A critical review of the effectiveness of rodent pharmaceutical carcinogenesis testing in predicting for human risk.

The pharmaceutical industry and regulatory agency toxicology testing paradigms in the United States currently appear successful, in part because of the continuously increasing life expectancy and the declining age-adjusted cancer rates in the United States. Although drugs likely have a minimal impact on the population statistics for cancer rates, pharmaceutical pathologists and toxicologists must focus on the individual risk for pharmaceutical carcinogenesis. As our understanding of carcinogenesis increases exponentially, and after hundreds if not thousands of rodent cancer tests, significant improvement in the precision of human pharmaceutical carcinogenesis hazard identification should now be possible and would enable a reduction in the substantial false-negative and false positive-rates reported herein. The appropriate use of acute, subchronic, chronic, and special toxicology tests to identify the major associated cancer risk factors, specifically, hormonal modulation, immunosuppression, genetic toxicity, and chronic toxicity, can be recognized through this review of pharmaceutical carcinogens. Significant opportunities exist for improving the effectiveness and efficiency of the current cancer risk assessment paradigm.