Predictive strategies for selecting 379 NCI/NTP chemicals evaluated for carcinogenic potential: scientific and public...

The a priori criteria used by the National Cancer Institute/National Toxicology Program (NCI/NTP) are described for 379 chemicals selected and evaluated for carcinogenic potential. We classified the chemicals according to exposure and structural categories and evaluated the predictive ability of the scientific selection criteria of chemicals suspected of being carcinogenic in advance of any study. Of the 379 chemicals, 253 (67%) were selected with a suspicion of carcinogenicity; 171 (68%) of these 253 chemicals induced cancer in at least one of the sex-species experiments. The other 126 (33%) chemicals were selected mainly, but not exclusively, on the basis of exposure considerations and production volumes; only 27 (21%) of these were judged to be positive. Overall, 198 (52%) of the 379 chemicals studied induced tumors in at least one organ of one sex of one species, but only 87 (23%) of these 379 chemicals were positive in both species and are considered most likely to present carcinogenic hazards to humans. Importantly, 78 (90%) of these 87 chemicals were selected with a prospective suspicion of carcinogenicity. Although the program has studied only a part of the "Universe of Chemicals" (defined as chemicals to which humans are exposed), the scientific data generated are essential for developing structure activity data bases of potentially hazardous chemical classes and for predicting the carcinogenicity of chemicals not yet studied. Thus, the bioassay program has had beneficial and crucial impacts on public health, as demonstrated by the use of these data by international, Federal, and State regulatory agencies to reduce or eliminate exposures to chemicals shown to be unequivocally carcinogenic in laboratory animals.