QSAR in Toxicology. 3. Prediction of Chronic Toxicities

A critical review is given of quantitative and qualitative structure‐activity relationships (QSAR) for the prediction of some chronic toxicological endpoints required for regulatory purposes. Many methodological approaches have been applied to the prediction of carcinogenicity and mutagenicity based on either identification of the molecular substructures that account for electrophilic reactivity or quantitative description of the hydrophobicity and reactivity of the molecule. A recent blind trial, however, found the opinion of human experts still to be most successful. Analyses of the interrelationship between carcinogenicity and mutagenicity data are also discussed. Relatively little work has been performed in the QSAR analysis of developmental toxicity. This whole area is hindered by a lack of quality in vivo toxicity data to model, and by the mechanisms of action not being fully understood.