郑子廷, 闫赛红, 查金苗. 有机磷类化合物大鼠急性毒性QSAR模型构建与毒性机制研究[J]. 生态毒理学报, 2022, 17(1): 150-159. doi: 10.7524/AJE.1673-5897.20211213002
引用本文: 郑子廷, 闫赛红, 查金苗. 有机磷类化合物大鼠急性毒性QSAR模型构建与毒性机制研究[J]. 生态毒理学报, 2022, 17(1): 150-159. doi: 10.7524/AJE.1673-5897.20211213002
Zheng Ziting, Yan Saihong, Zha Jinmiao. Development of QSAR Models for Acute Toxicity of Organophosphorus Compounds towards Rats and Study of Toxicity Mechanism[J]. Asian Journal of Ecotoxicology, 2022, 17(1): 150-159. doi: 10.7524/AJE.1673-5897.20211213002
Citation: Zheng Ziting, Yan Saihong, Zha Jinmiao. Development of QSAR Models for Acute Toxicity of Organophosphorus Compounds towards Rats and Study of Toxicity Mechanism[J]. Asian Journal of Ecotoxicology, 2022, 17(1): 150-159. doi: 10.7524/AJE.1673-5897.20211213002


    作者简介: 郑子廷(1997-),男,硕士研究生,研究方向为环境毒理学,E-mail:zztsaigo@126.com
    通讯作者: 闫赛红, E-mail: shyan@rcees.ac.cn 查金苗, E-mail: jmzha@rcees.ac.cn
  • 基金项目:


  • 中图分类号: X171.5

Development of QSAR Models for Acute Toxicity of Organophosphorus Compounds towards Rats and Study of Toxicity Mechanism

    Corresponding authors: Yan Saihong, shyan@rcees.ac.cn ;  Zha Jinmiao, jmzha@rcees.ac.cn
  • Fund Project:
  • 摘要: 有机磷化合物(OPs)广泛分布在各种环境介质中,并对各类生物的健康有潜在的危害。本研究采用基于逐步算法(SW)和遗传算法(GA)的多元线性回归(MLR)方法,收集并筛选出53种OPs的数据集并建立其关于大鼠急性口服毒性(LD50)的定量结构活性关系(QSAR)模型。构建的SW-MLR模型的参数决定系数(R2)、留一法交叉验证系数(Q2LOO)、外部检验系数(Q2F1Q2F2)分别为0.897、0.817、0.515和0.505,GA-MLR模型的参数分别为0.827、0.752、0.831和0.828。2个模型的统计参数表征了良好的预测能力。使用外部测试集对模型进行评估时,发现GA-MLR模型比SW-MLR模型具有更好的预测和泛化能力。此外,基于建立的模型预测了其他9种OPs的急性毒性,并辅以分子对接技术探究了其潜在的神经毒性。分子对接结果显示,其中8种OPs可以与人类丁酰胆碱酯酶结合。模型机理解释和分子对接结果显示,OPs取代基的高烷基化程度和支链长度的增加能够降低毒性。因此,建立的模型可以从OPs的分子结构上探索与毒性相关的信息,并为监管和筛选新的OPs提供基础数据。
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  • 收稿日期:  2021-12-13


    通讯作者: 闫赛红, E-mail: shyan@rcees.ac.cn ;  查金苗, E-mail: jmzha@rcees.ac.cn
    作者简介: 郑子廷(1997-),男,硕士研究生,研究方向为环境毒理学,E-mail:zztsaigo@126.com
  • 1. 中国科学院生态环境研究中心, 环境水质学国家重点实验室, 北京 100085;
  • 2. 中国科学院大学, 北京 100049


摘要: 有机磷化合物(OPs)广泛分布在各种环境介质中,并对各类生物的健康有潜在的危害。本研究采用基于逐步算法(SW)和遗传算法(GA)的多元线性回归(MLR)方法,收集并筛选出53种OPs的数据集并建立其关于大鼠急性口服毒性(LD50)的定量结构活性关系(QSAR)模型。构建的SW-MLR模型的参数决定系数(R2)、留一法交叉验证系数(Q2LOO)、外部检验系数(Q2F1Q2F2)分别为0.897、0.817、0.515和0.505,GA-MLR模型的参数分别为0.827、0.752、0.831和0.828。2个模型的统计参数表征了良好的预测能力。使用外部测试集对模型进行评估时,发现GA-MLR模型比SW-MLR模型具有更好的预测和泛化能力。此外,基于建立的模型预测了其他9种OPs的急性毒性,并辅以分子对接技术探究了其潜在的神经毒性。分子对接结果显示,其中8种OPs可以与人类丁酰胆碱酯酶结合。模型机理解释和分子对接结果显示,OPs取代基的高烷基化程度和支链长度的增加能够降低毒性。因此,建立的模型可以从OPs的分子结构上探索与毒性相关的信息,并为监管和筛选新的OPs提供基础数据。

English Abstract

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