Development of quantitative structure-activity relationships for the toxicity of aromatic compounds to Tetrahymena pyriformis: Comparative assessmentof the methodologies

The purpose of this study was to develop quantitative structure-activity re lationships (QSARs) for the toxicity of 268 aromatic compounds in the Tetra hymena pyriformis growth inhibition assay. The QSARs were developed using t he response-surface (or two-parameter) approach, which was also modified us ing linear free-energy parameters to account for outliers. Subsequently, th e data set was analyzed using partial least-squares (PLS). The results of t he modeling using different methodologies were compared to the use of a Bay esian regularized neural network (BRANN) trained on the same data. Both res ponse surface approaches, and PLS explained between 75 and 80% of the varia nce in the data; BRANN gave a higher statistical fit. In terms of the trans parency of the approaches, the response surface clearly provides the simple st and easiest to use QSAR, it is readily interpreted in terms of mechanism of toxic action. PLS and BRANN are respectively less transparent. The use of atomistic and fragment-based indexes as descriptors in QSARs is assessed also, these are found not to be as useful as whole molecule parameters for the prediction of toxicity for molecules outside of the training set. The relative merits of the different approaches to the development of QSARs are described.