POTENCY GRADING IN CARCINOGEN CLASSIFICATION

In 1992 the United Nations Conference on Environment and Development d ecided to harmonize carcinogen classification systems. A proposal for a harmonized classification system is currently being considered by th e Organization for Economic Cooperation and Development (OECD). In man y countries, classification of a chemical as carcinogenic triggers lab eling requirements. implicit in the labeling requirements are often re strictions on the sale of consumer products and workplace regulations. Many of the current classification systems for carcinogens use a sing le concentration limit for the minimum concentration of a carcinogen i n a preparation (mixture) that requires labeling. For high-potency car cinogens, one concentration limit may not adequately express the hazar d, whereas for low-potency carcinogens, one limit may overestimate the hazard caused by the carcinogen in the preparation (mixture). The pot ency grading system discussed consists of three potency groups: high-, medium-, and low-potency carcinogens. it is envisioned that the diffe rent classes will trigger different labeling requirements. In the proc ess of potency grading, a preliminary conclusion as to whether a subst ance shows high, medium, or low potency is initially based on a tumori genic dose descriptor. The preliminary potency evaluation may then be modified after due consideration of a number of additional elements. T hese may include evaluation of the dose-response curve; site-, species -, strain-, and sex-specific activity; mechanisms including genotoxici ty; mechanistic relevance to humans; toxicokinetics; and other factors . The potency grading system discussed is applicable to most carcinoge n classification systems, including that currently being considered by the OECD. (C) 1997 Wiley-Liss, Inc.