Harmonization of cancer and noncancer risk assessment: Proceedings of a consensus-building workshop

Significant advancements have been made toward the use of all relevant scie ntific information in health risk assessments, This principle has been set forth in risk-assessment guidance documents of international agencies inclu ding those of the World Health Organization's International Programme on Ch emical Safety, the U.S, Environmental Protection Agency, and Health Canada. Improving the scientific basis of risk assessment is a leading strategic g oal of the Society of Toxicology. In recent years, there has been a plethor a of mechanistic research on modes of chemical toxicity that establishes me chanistic links between noncancer responses to toxic agents and subsequent overt manifestations of toxicity such as cancer. The research suggests that differences in approaches to assessing risk of cancer and noncancer toxici ty need to be resolved and a common broad paradigm for dose-response assess ments developed for all toxicity endpoints. In November 1999, a workshop en titled "Harmonization of Cancer and Noncancer Risk Assessment" was held to discuss the most critical issues involved in developing a more consistent a cid unified approach to risk assessment for all endpoints. Invited particip ants from government, industry, and academia discussed focus questions in t he areas of mode of action as the basis for harmonization, common levels of adverse effect across toxicities for use in dose-response assessments, and scaling and uncertainty factors. This report summarizes the results of tho se discussions. There was broad agreement, albeit not unanimous, that curre nt science supports the development of a harmonized set of principles that guide risk assessments for all toxic endpoints. There was an acceptance amo ng the participants that understanding the mode of action of a chemical is ultimately critical for nondefault risk assessments, that common modes of a ction for different toxicities can be defined, and that our approach to ass essing toxicity should be biologically consistent.