对孕妇中五二暴露的生理基础毒动力学 (PBTK) 建模的贝叶斯分析
Chunfeng Wu1, Yajiao Tan2, Xiaoyi Wei3
1Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China.
概括
一个新的基于生理学的毒动力学模型准确地预测了人类的五二醇 (PCP) 水平. 这种药理动力学模型改善了对环境污染物 (如PCP) 的风险评估.
科学领域:
- 环境毒理学环境毒理学
- 药理动力学 药理动力学
- 基于生理学的药物动力学建模.
背景情况:
- 五二 (PCP) 是一种持久性环境污染物.
- 通过毒动力学模型准确估计内部暴露对于PCP对人类健康的风险评估至关重要.
- 现有的模型需要改进,以预测人类的PCP行为.
研究的目的:
- 开发和验证一个基于生理学的多分部药理动力学 (PBTK) 模型用于五二 (PCP).
- 为了预测大鼠的PCP行为,并推断到人类的饮食暴露.
- 用人类数据优化模型,以改善风险评估.
主要方法:
- 构建一个PBTK模型,包括关键的生理部位 (胃,肠,脂肪组织,脏等). ) 的情况.
- 从大鼠模型推断出人类饮食暴露,使用已发表的毒动力学数据.
- 贝叶斯统计分析与马尔科夫链蒙特卡洛 (MCMC) 模拟用于参数优化和验证,使用来自上海的孕妇数据.
主要成果:
- 与原始模型相比,优化的PBTK模型在根平均平方误差 (RMSE) 中表现出37.3%的改善.
- 该模型在中国的其他数据集中取得了可接受的预测结果,表明了良好的概括性.
- 确定了敏感的参数,并根据真实世界的暴露数据验证了模型.
结论:
- 已成功构建了对五二 (PCP) 的验证PBTK模型,该模型专门针对中国孕妇的暴露特征而定制.
- 优化模型为了解PCP毒性和进行准确的人类健康风险评估提供了强大的理论框架.
- 这项研究提高了评估与PCP等环境污染物相关的风险的能力.
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