Predicting mutagenicity of congeneric and diverse sets of chemicals using computed molecular descriptors: A hierarchical approach

Mutagenicity of chemicals is an important toxicological endpoint because it is useful for the qualitative prediction of rodent carcinogenicity and, therefore, potential human carcinogenicity of substances. ¹ As a result, various congeneric and noncongeneric groups of chemicals have been subjected to the Salmonella typhimurium (Ames test) bioassay to determine their mutagenicity. ² Currently, the government and society in general are greatly interested in developing strategies for the assessment of risk posed by the myriads of chemicals that are used routinely for industrial, cosmetic, agricultural, diagnostic, and therapeutic purposes. In the area of industrial chemicals, under pressure from the U.S. government and environmental organizations, the American Chemistry Council (ACC) has undertaken a program of testing about 2800 high-production-volume (HPV) chemicals at a cost of approximately $700 million. This project is slated for completion by 2004. Even if it is completed in time, a substantial problem of estimating toxicity of chemicals existing in the Toxic Substances Control Act (TSCA) inventory will still linger, because the inventory currently has over 81,000 entries. Most of these TSCA chemicals have no experimental data that can be used for the prediction of toxicity and ecotoxicy, ³ and only 15% of the TSCA substances have mutagenicity data.