Topics in cancer risk assessment.

The estimation of carcinogenic risks from exposure to chemicals has become an integral part of the regulatory process in the United States within the past decade. With it have come considerable controversy and debate over the scientific merits and shortcomings of the methods and their impact on risk management decisions. In this paper we highlight selected topics of current interest in the debate. As an indication of the level of public concern, we note the major recent reports on risk assessment from the National Academy of Sciences and the U.S Environmental Protection Agency's proposed substantial revisions to its Guidelines for Carcinogen Risk Assessment. We identify and briefly frame several key scientific issues in cancer risk assessment, including the growing recognition of the importance of understanding the mode of action of carcinogenesis in experimental animals and in humans, the methodologies and challenges in quantitative extrapolation of cancer risks, and the question of how to assess and account for human variability in susceptibility to carcinogens. In addition, we discuss initiatives in progress that may fundamentally alter the carcinogenesis testing paradigm.