The future of mechanistic research in risk assessment: Where are we going and can we get there from here?

Quantitative estimates of human health risk are often based on mathematical models fit to experimental or epidemiological data. Recent years have witnessed a trend towards the use of mechanistic models in risk assessment applications. Such models afford a more biologically based interpretation of the data and a firmer scientific basis for extrapolation beyond the conditions under which the original data were obtained. In this article, we review some recent advances in the development of biologically based models for mutagenesis, carcinogenesis and developmental toxicity. Pharmacokinetic and receptor-binding models and their roles in mechanistic risk assessment are also discussed. The future of mechanistic research in risk assessment is contemplated, including the need for more elaborate experiments to obtain the data necessary for mechanistic modeling.