RODENT CARCINOGENICITY BIOASSAY - PAST, PRESENT, AND FUTURE

Toxicity/carcinogenicity studies in rodents have played a pivotal role in identifying chemicals that are potentially hazardous to humans. In fact, nearly all of the known human carcinogens are also carcinogenic in 1 or more rodent species. During the past 20 yr the quality and co nsistency of rodent studies has improved considerably, and much has be en learned about mechanisms whereby chemicals initiate or promote the carcinogenic process in rats and mice. The process of identifying chem icals that cause toxicity or carcinogenicity in rodents is quite well established, but the procedures for extrapolating this data for risk m anagement decisions in the protection of human health have lagged far behind. While many would accept the assumptions that genotoxic chemica ls that cause cancer in animals pose a cancer risk to humans and that genotoxic chemicals causing cancer at high doses pose a risk at lower doses, there is much less certainty with respect to nongenotoxic chemi cals. The confusion about risk extrapolation for nongenotoxic chemical s has often lead to criticism of the hazard identification process for chemicals in general. There is increasing awareness of the complexity of the carcinogenic process that has made species extrapolation and d ose extrapolation from rodent studies to humans more complex. Although newer molecular biological techniques and cell kinetic measurements o ffer exciting possibilities for better risk assessment, it is the comb ination of well-designed rodent studies with appropriate mechanistic s tudies that offers the best hope for regulatory decisions based on sou nd scientific principles.