A paradigm for determining the relevance of short-term assays: application to oxidative mutagenesis.

A simple substructure-based approach was developed to determine whether a short-term assay under development is related mechanistically to the endpoint it seeks to predict. Thus, substructures associated with mutagenicity in Salmonella are also present in carcinogens and agents active in other mutagenicity and genotoxicity assays. When applied to test results obtained with an Escherichia coli strain designed to identify oxidative mutagens, there was no significant association with either carcinogens or mutagens and genotoxicants detected by other systems. There was, however, a significant association between alerts for oxidative mutagenesis and chemicals capable of inducing allergic contact dermatitis (ACD) in humans.