Prediction of mutagenicity of aromatic and heteroaromatic amines from structure: A hierarchical QSAR approach

Due to the lack of experimental data, there has been increasing use of theo retical structural descriptors in the hazard assessment of chemicals. We ha ve used a hierarchical approach to develop class-specific quantitative stru cture-activity relationship (QSAR) models for the prediction of mutagenicit y of a set of 95 aromatic and heteroaromatic amines. The hierarchical appro ach begins with the simplest molecular descriptors, the topostructural, whi ch encode limited chemical information. The complexity is then increased, a dding topochemical, geometric, and finally quantum chemical parameters. We have also added log P to the set of independent variables. The results indi cate that the topological parameters, i.e., the topostructural and topochem ical indices, explain the majority of the variance, and that the inclusion of log P, geometric, and quantum chemical parameters does not result in sig nificantly improved predictive models.