一个基于人群生理学的动力学和毒力学模型,用于急性迪亚津暴露
Jiaqi Chen1, Bingxu Chen1, Sebastiaan Wesseling1
1Division of Toxicology, Wageningen University and Research, Stippeneng 4, Wageningen, Gelderland 6708 WE, the Netherlands.
Ecotoxicology and environmental safety
|March 27, 2025
概括
这项研究开发了一种人口模型,以评估来自有机酸盐农药暴露的风险. 它发现人体如何处理化学物质的个体差异,而不是化学物质.
科学领域:
- 环境毒理学环境毒理学
- 计算毒理学计算毒理学
- 风险评估 风险评估 风险评估
背景情况:
- 有机 (OP) 农药是常见的环境污染物.
- 通过乙胆酶 (AChE) 抑制,急性OP暴露带来神经毒性风险.
研究的目的:
- 开发一个基于人群的生理学基础的动力学和毒力学 (PBK-TD) 模型.
- 为了建立一个基于健康的指导值 (HBGV) 对于急性迪亚津暴露.
- 为了考虑到人类在生理学,毒动力学和毒动力学方面的个体间的变化.
主要方法:
- 使用了整合PBK-TD建模的新方法方法 (NAM).
- 从文献和in silico-in vitro方法中收集了特定的生理和化学输入.
- 采用蒙特卡洛模拟来产生剂量依赖的ACHE抑制并推导出出发点 (POD).
主要成果:
- 该PBK-TD模型准确地模拟了人类的毒动力学和毒性数据.
- 毒动力学变化,而不是毒动力学变化,是敏感性变化的主要驱动因素.
- 敏感成年人预测的POD与现有的人类无观察不良影响水平 (NOAELs) 相一致.
结论:
- 人口PBK-TD建模为在人类健康风险评估中推导POD提供了一种新的方法.
- 该模型成功地结合了个体间的敏感性差异.
- 未来的改进包括参数相关性和组织特异性胆酶抑制.
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