Carcinogen testing: current problems and new approaches.

The classic procedures for testing potential carcinogens in animals have basically not changed in the past 50 years. Considerable knowledge of the mechanisms of carcinogenesis has accrued in the last 20 years, particularly concepts on the metabolic activation of chemicals to reactive electrophilic compounds that can interact with nucleophilic including DNA. These developments, in turn, have yielded a framework for integrating into carcinogen testing the determination of genetic effects of chemicals. A systematic decision point approach to carcinogen testing has been developed which entails a sequential decision-making process as specific tests are performed and evaluated prior to initiation of higher order, more complex tests. Compared to conventional bioassays in rodents, this approach provides knowledge based on mechanisms of carcinogenesis, yields a substantial amount of data at minimal cost, and forms a solid base for eventual heath risk assessment.