Risk Assessment Is a Developing Science: Approaches to Improve Evaluation of Single Chemicals and Chemical Mixtures

The Environmental Criteria and Assessment Office of Cincinnati, of the US Environmental Protection Agency, is engaged in the development of risk assessment guidelines and methodologies as part of the regulatory programme of the Agency. The primary goal of the Agency was originally to accurately assessthe effects of human exposure to single chemicals in a single medium (e.g.water) over a human lifetime. Assessment methods for estimating low-dose lifetime cancer risk for known or suspected human carcinogens, or long-term acceptable daily intake (ADI) levels for threshold-acting toxicants, were developed and successfully applied to meet this need. Now, there is an increasing need for methods which address more complex exposure situations, including multichemical, multiroute, and partial-lifetime exposures. Improvements in the current methods are also needed. Several issues now under study will be briefly described. To convert animal dose to equivalent human dose, an approach based on body surface area is being considered as an improvemen t to curren t methods which use body weight. To assess effects of less-than-lifetime exposures, separate approaches for carcinogens and non-carcinogens are proposed. Existing low-dose extrapolation models have been modified to enable prediction of cancer incidence at a variety of exposure durations. For non-carcinogens, a graphical method for displaying dose-duration~ffect relationships, which permits interpolation to any exposure duration, has been developed. Methods for determining equivalent doses for different exposure routes (e.g. inhalation versus ingestion) are straightforward for chemicals with certain toxicological characteristics, but demand specificknowledge of pharmacokinetic