RISK ASSESSMENT AND THE USE OF INFORMATION ON UNDERLYING BIOLOGIC MECHANISMS - A PERSPECTIVE

Recent years have seen the rapid expansion of scientific understanding of the underlying biologic bases of toxic reactions to chemicals. Use of this information in health risk assessment is expanding, but it ha s yet to reach its full potential. This article considers what has suc cessfully been done, what approaches are now being developed, and what impediments and difficulties have been encountered in attempts to bri ng case-specific, mechanistic toxicological information to bear on ris k estimation. In hazard identification, mechanistic information can he lp explain the bearing of various empirical experimental results for i nferring human hazard, can increase the sensitivity of detection, and can be considered in attempts to replace 2-year animal bioassays with hazard identification methods that rest on identifying key biological properties underlying carcinogenicity rather than relying only on the experimental observation of tumors. In carcinogen potency estimation, mechanistic information can potentially extend relevant observation to lower dose levels, provide the basis for choosing among empirically b ased dose-response models, lead to potency estimates through relations hips with quantitative measures of shea-term test outcomes, acid can b e considered as a basis for providing direct observation of the biolog ical parameters in biologically based dose-response modeling.