Potency grading in carcinogen classification.

In 1992 the United Nations Conference on Environment and Development decided to harmonize carcinogen classification systems. A proposal for a harmonized classification system is currently being considered by the Organization for Economic Cooperation and Development (OECD). In many countries, classification of a chemical as carcinogenic triggers labeling requirements. Implicit in the labeling requirements are often restrictions on the sale of consumer products and workplace regulations. Many of the current classification systems for carcinogens use a single concentration limit for the minimum concentration of a carcinogen in a preparation (mixture) that requires labeling. For high-potency carcinogens, one concentration limit may not adequately express the hazard, whereas for low-potency carcinogens, one limit may overestimate the hazard caused by the carcinogen in the preparation (mixture). The potency grading system discussed consists of three potency groups: high-, medium-, and low-potency carcinogens. It is envisioned that the different classes will trigger different labeling requirements. In the process of potency grading, a preliminary conclusion as to whether a substance shows high, medium, or low potency is initially based on a tumorigenic dose descriptor. The preliminary potency evaluation may then be modified after due consideration of a number of additional elements. These may include evaluation of the dose-response curve; site-, species-, strain-, and sex-specific activity; mechanisms including genotoxicity; mechanistic relevance to humans; toxicokinetics; and other factors. The potency grading system discussed is applicable to most carcinogen classification systems, including that currently being considered by the OECD.

Carcinogen classification systems: similarities and differences.

An overview of regulatory classification systems on carcinogens in the Organization for Economic Cooperation and Development (OECD) countries is presented based on a questionnaire study. Most OECD countries have implemented legislation including classification systems and lists of carcinogens. Basically, there are two types of classifications systems. The major difference between the two is that in one system carcinogens are classified according to the weight of evidence for carcinogenic effects in humans, whereas in the other carcinogens are allocated to various groups according to potency. Even if the classification systems may differ, the substances classified as carcinogens are to a large extent the same. Classification of carcinogens will in many countries require hazard labeling. This labeling, i.e., the limit for labeling of substances and preparations, and risk phrases show considerable similarities, but differ in certain aspects. Several countries have restrictions on sale and/or use of carcinogens. There is a trend toward introducing more mechanistic considerations in the classification of carcinogens.