CAN BIOLOGICALLY BASED MODELS OF CARCINOGENESIS BE USED FOR RISK ASSESSMENT ? Potentials and limitations of carcinogenesis models

摘要

In their 1996 proposed guidelines, the United States Environmental Protection Agency (US EPA 1996) suggest the use of biologically based carcinogenesis models for low dose risk estimation in cancer risk assessment whenever sufficient data are available in sup port of the model. In this contribution, an overview of carcinogenesis models is presented and the models are classified according to their ability to incorporate biological detail. The utility of these models for risk assessment is discussed and two different applications are distin-guished: either the models can be used for low-dose extrapolation or for risk prediction. In the. first application, one has to cope with two challenges: to carefully select the model for correct representation of the mechanism and to then choose the appropriate dose-response relation ship for each model parameter. As an example of risk prediction, the model can be used to analyze scenarios for different dose-response relationships of the model parameters and their impact on the shape of lifetime tumor probability.