Commentary on EPA carcinogen risk assessment guidelines.

EPA has indicated the Agency's Cancer Risk Assessment Guidelines are intended to be evergreen, i.e., subject to revision as advances are made in scientific understanding or difficulties are encountered. Several changes could be made in the Guidelines to better utilize advances in science, some of which EPA has already incorporated into risk assessment procedures, and also to alleviate difficulties encountered by the Agency. The hazard identification step of risk assessment should be more clearly defined, especially with respect to describing the best use of animal data to predict human hazard. The classification system for summarizing carcinogenic hazard should be expanded, and the titles revised, to better describe the varying degrees of knowledge concerning human carcinogenic hazard derived from experimental data. Current dose response estimation procedures should be supplemented to provide risk managers more perspective on human risk. Suggested additions are a central estimate of the upper bound of the dose response curve and a most plausible estimate of human response as a function of dose. The central estimate of the upper bound still includes the calculation of a statistical upper limit, but utilizes central estimates for some of the critical policy options. The most plausible estimate relies heavily on evaluation of the mechanism of carcinogenic activity and its implications for dose response estimation in humans. Thus, the outcome of dose response evaluation would include the current upper bound (worst case), a more central estimate of the upper bound, a most plausible estimate, and the lower bound.