New directions for predicting carcinogenesis.

Carcinogenicity testing today normally includes conducting 2-yr studies of rats and mice of both sexes and following widely accepted procedures for husbandry, selection of dose levels, pathology and toxicity observations, and statistical interpretation of tumor data. These studies are usually preceded by tests for genetic toxicity and subchronic toxicity studies to select dose levels for the 2-yr studies. While these data are used for quantitative risk assessment, the mechanistic basis for effects is usually unknown, and such series of studies are very expensive and require five or more years to conduct. Alternate approaches are being developed that would provide more mechanistic information and perhaps would permit decisions to be made about carcinogenic potential without the need to conduct 2-yr studies of rats and mice of both sexes. Decisions could be based on a profile of data rather than the result of one test. Regulatory acceptance of new approaches for carcinogenicity testing is critical to future progress in the field of carcinogenesis.