人类生物监测和毒动力学作为下一代风险评估的关键组成部分
Elena Reale1, Maryam Zare Jeddi2, Alicia Paini3
1Centre for Primary Care and Public Health (Unisanté), University of Lausanne, Switzerland.
Environment international
|February 13, 2024
概括
下一代风险评估 (NGRA) 可以通过将人类生物监测 (HBM) 与毒动力学 (TK) 和生理基动力学 (PBK) 建模相结合来改进. 这种转变是从动物试验转向与人类相关的内部暴露评估,以更准确地评估化学安全.
科学领域:
- 毒理学和环境健康
- 计算生物学和生物信息学
背景情况:
- 传统的人类健康风险评估主要依赖于动物试验和经合组织指导方针.
- 下一代风险评估 (NGRA) 的进展侧重于新方法方法 (NAM) 和基于生理的动力学 (PBK) 建模.
- 然而,NGRA经常忽视了人类生物监测 (HBM) 数据的整合.
研究的目的:
- 详细介绍化学风险评估中毒动力学 (TK),PBK建模和HBM的综合使用.
- 为NGRA强调将HBM纳入TK/PBK建模中的机遇,挑战和局限性.
- 为了证明转向无动物,基于内部暴露的风险评估.
主要方法:
- 对TC,PBK建模和HBM的集成进行审查和阐述.
- 讨论这些方法如何提高暴露评估和危害特征.
- 展示HBM和TK/PBK建模的应用的示例.
主要成果:
- 将HBM与TCK和PBK建模的整合加强了NGRA方法,并减少了不确定性.
- PBK模型对于定量描述TK过程和有效的目标部位剂量至关重要.
- 结合 TK/PBK 建模和 HBM 便于评估聚合/累积暴露和化学混合物.
结论:
- 将HBM与TK和PBK建模集成,对于推进NGRA至关重要.
- 这种整合使得可以从外部的,以动物为基础的暴露评估转向内部的,与人类相关的暴露评估.
- 拟议的方法为化学风险评估提供了一种更为特定于物种和基于机制的途径.
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