Exploring QSAR models for assessment of acute fish toxicity of environmental transformation products of pesticides (ETPPs)

摘要

Environmental transformation products of pesticides (ETPPs) have a great deal of ecological impact owing to their ability to cause toxicity to the aquatic organisms, which can then be translated to the humans. The limited experimental data on biochemical and toxic effects of ETPPs, the high test costs together with regulatory limitations and the international push to reduce animal testing encourage greater dependence on predictive in silico techniques like quantitative structure-activity relationship (QSAR) models. The aim of the present work was to explore the key structural features, which regulate the toxicity towards fishes, for 85 ETPPs using a partial least squares (PLS) regression based chemometric model developed according to Organisation for Economic Co-operation and Development (OECD) guidelines. The model was extensively validated using both internal and external validation metrics, and the results so obtained justify the reliability and usefulness of the developed model (Q(2) = 0.648, R-pred(2) or Q(F1)(2) = 0.734 and Q(F2)(2) = 0.733). From the developed model, we can conclude that lipophilicity, polarity, presence of branching and the functional form of 0-atom in the transformed structures of pesticides are the important features that are to be considered during ecotoxicity assessment of ETPPs. The information obtained from the descriptors of the developed model could be utilized in the future for assessing ETPPs with the benefit of providing an early warning of their potentially detrimental effect on fishes for regulatory purposes. (C) 2020 Elsevier Ltd. All rights reserved.