FUTURE APPROACHES TO GENETIC TOXICOLOGY RISK ASSESSMENT

Short-term genetic toxicology tests were developed for the purpose of identifying chemical carcinogens in the environment. After two decades of development and validation, the tests are well-established in rout ine testing schemes, but our views of their utility for safety evaluat ion have undergone re-assessment. The correlation between identified m utagens and identified carcinogens has turned out to be significantly less than one, Processes or mechanisms that are not directly genotoxic appear to play a role in carcinogenesis. While short term test data a re still components of the assessment of carcinogenic risk, genetic da mage also has been recognized as important in its own right, in relati on to heritable genetic risk and other health-related effects, such as aging, reproductive failure and developmental toxicity. The revolutio n in molecular biology and genetic analysis occurring over the past 20 years has contributed to the wealth of new information on the complex ities of cell regulation, differentiation, and the carcinogenic proces s. These technologies have provided new experimental approaches to gen etic toxicology assessments, including transgenic cell and animal mode ls, human monitoring, and analysis of macromolecular interactions at e nvironmentally relevant exposures. The potential exists for the develo pment of more efficient and more relevant genetic toxicology testing s chemes for use assessing human safety. A delineation of contemporary n eeds, a modem view of the elements of cancer induction, and an examina tion of new assays and technologies may provide a framework for integr ating new approaches into current schemes for evaluating the potential genetic and carcinogenic risk of environmental chemicals.