Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India.
Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India.
Chemosphere. 2020 Aug;252:126508. doi: 10.1016/j.chemosphere.2020.126508. Epub 2020 Mar 18.
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 = 0.648, R or Q = 0.734 and Q = 0.733). From the developed model, we can conclude that lipophilicity, polarity, presence of branching and the functional form of O-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.
由于能够对水生生物造成毒性，农药的环境转化产物（ETPPs）对生态有很大的影响，而这种毒性继而可能会转移到人类身上。关于 ETPPs 的生化和毒性影响的有限实验数据、高测试成本以及监管限制，再加上减少动物测试的国际推动，都鼓励更多地依赖预测性的计算技术，如定量构效关系（QSAR）模型。本工作的目的是使用根据经济合作与发展组织（OECD）指南开发的基于偏最小二乘（PLS）回归的化学计量学模型，探索 85 种 ETPPs 对鱼类毒性的关键结构特征。该模型通过内部和外部验证指标进行了广泛验证，所得结果证明了所开发模型的可靠性和有用性（Q = 0.648、R 或 Q = 0.734 和 Q = 0.733）。从所开发的模型中，我们可以得出结论，亲脂性、极性、分支的存在以及农药转化结构中 O 原子的官能团形式是在评估 ETPPs 的生态毒性时需要考虑的重要特征。从所开发模型的描述符中获得的信息可用于未来评估 ETPPs，以便为监管目的提供其对鱼类潜在有害影响的早期预警。
