Flexible use of QSAR models in predictive toxicology: a case study on aromatic amines

Over the last years, predictive toxicology approaches based on Structure-Activity Relationships have emerged as fundamental tools in the regulatory assessments of chemicals, especially in those programs where regulatory constraints and assessment schemes limit the amount of data available from experimental test methods. Both the qualitative (e.g., Structural Alerts) and the quantitative (Quantitative Structure-Activity Relationships, QSAR) approach can play important roles. However, the two approaches are not familiar to the same extent to the regulators that most often use only the qualitative approach, so that the potentiality of the more sophisticated QSAR approach is neglected. In fact, QSAR is a very flexible tool that allows the user to modulate its response according to different goals and requirements. Here, we present a non-naïve approach to the use of a QSAR relative to a dichotomous biological activity (such as mutagen/nonmutagen), and we show how the user can maximize alternatively the reliability of the prediction of negative compounds (i.e., safe chemicals) or that of positive chemicals (i.e., chemicals that pose high hazard). Because of the environmental and industrial importance of the class of aromatic amines, we apply the approach to a previously published QSAR on the Salmonella typhimurium mutagenicity of these chemicals.