A novel approach to predict aquatic toxicity from molecular structure

The main aim of the study was to develop quantitative structure-activity relationship (QSAR) models for the prediction of aquatic toxicity using atom-based non-stochastic and stochastic linear indices. The used dataset consist of 392 benzene derivatives, separated into training and test sets, for which toxicity data to the ciliate Tetrahymena pyriformis were available. Using multiple linear regression, two statistically significant QSAR models were obtained with non-stochastic (R² = 0.791 and s = 0.344) and stochastic (R² = 0.799 and s = 0.343) linear indices. A leave-one-out (LOO) cross-validation procedure was carried out achieving values of q² = 0.781 (s_cv = 0.348) and q² = 0.786 (s_cv = 0.350), respectively. In addition, a validation through an external test set was performed, which yields significant values of R_pred² of 0.762 and 0.797. A brief study of the influence of the statistical outliers in QSAR's model development was also carried out. Finally, our method was compared with other approaches implemented in the Dragon software achieving better results. The non-stochastic and stochastic linear indices appear to provide an interesting alternative to costly and time-consuming experiments for determining toxicity.