Development and validation of theoretical linear solvation energy relationship models for toxicity prediction to fathead minnow (Pimephales promelas)

Abstract

The acute toxicity predictive models are vitally important for the toxicological information used in the ecological risk assessments. In this study, we used Verhaar classification scheme to group compounds into five modes of toxic action. The quantum chemical descriptors that characterize the electron donor-acceptor property of the compounds were introduced into the theoretical linear solvation energy relationship (TLSER) models. The predictive models have relatively larger data sets, which imply that they cover a wide applicability domain (AD). All models were developed following the Organization for Economic Co-operation and Development (OECD) QSAR models development and validation guidelines. The adjusted determination coefficient (Radj(2)) and external explained variance (QEXT(2)) of the models were ranging from 0.707 to 0.903 and 0.660 to 0.858, respectively, indicating high goodness-of-fit, robustness and predictive capacity. The cavity term (McGowans volume) was the most significant descriptor in the models. Moreover, the electron donor-acceptor (E-TLSER) models are comparable to the TLSER models for the toxicity prediction to fathead minnow. Thus, the E-TLSER models developed can be used to predict acute toxicity of new compounds within the AD.

Keywords: Applicability domain; Electron donor–acceptor interaction; Fathead minnow; Mode of action; TLSER models.