通过不良结果途径的人体内分泌干扰甲酸的作用:全面的机制分析
Yunxiang Li1, Hao Yang1, Wei He1
1College of Environmental Science and Engineering, North China Electric Power University, Beijing 102206, China.
International journal of molecular sciences
|September 9, 2023
概括
甲酸 (PAE) 破坏人类内分泌系统. 机器学习模型确定了关键的分子特征和相互作用,定义了有害结果途径 (AOP) 来指导毒性研究.
科学领域:
- 环境化学环境化学
- 毒理学 毒理学 毒理学
- 计算化学的计算化学
背景情况:
- 甲酸 (PAE) 是常见的增塑剂,具有已知的内分泌干扰作用.
- 了解PAE内分泌干扰的分子机制对于人类健康风险评估至关重要.
研究的目的:
- 使用机器学习构建一种不良结果途径 (AOP),用于PAE对人类的内分泌干扰效应.
- 为了确定驱动PAE毒性的关键分子特征和相互作用.
主要方法:
- 应用了三种机器学习技术 (随机森林,XGBoost) 来构建一个AOP模型.
- 进行敏感性分析以确定关键的分子特征和事件.
- 开发了一个3D-QSAR模型,并分析了分子相互作用 (结合,疏水性,范德瓦尔斯力) 和结合能量.
主要成果:
- 随机森林和XGBoost模型显示了AOP的高预测性能.
- 关键的分子特征 (例如,Mol.Wt,Q+,E_LUMO) 和物理化学性质 (疏水性,固体性,静电场) 被确定为至关重要的.
- 确认结,疏水和范德瓦尔斯相互作用在PAE内分泌干扰中具有重要意义.
结论:
- 对人类PAE内分泌干扰建立了一个全面的AOP.
- 理论模拟方法可以有效地描述AOP,并提供有关污染物毒性机制的见解.
- 研究结果为评估PAE和类似环境污染物的健康风险提供了理论指导.
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