将人体暴露组数据整合到下一代风险评估中:一个系统的框架来推断现实暴露水平,并优先考虑测试化学化合物的化学化合物
Yifeng Dai1, Bob van de Water2, Jaione Telleria3
1Department of Global Public Health and Bioethics, Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands; Institute of Risk Assessment Sciences, Utrecht University, Yalelaan 2, 3584CM Utrecht, the Netherlands.
Environment international
|February 3, 2026
概括
本研究引入了一个框架,将暴露数据与下一代风险评估 (NGRA) 整合在一起,以加强化学安全评估. 纳入人类生物监测 (HBM) 数据显著改善了对人类健康的化学物质优先级.
科学领域:
- 环境健康科学 环境健康科学
- 毒理学 毒理学 毒理学
- 计算生物学 计算生物学
背景情况:
- 暴露体研究和下一代风险评估 (NGRA) 旨在提高化学安全评估中的人类相关性.
- 将暴露组数据实际集成到NGRA工作流中仍然是一个挑战.
- 现有的方法往往缺乏全面的人类暴露数据.
研究的目的:
- 为NGRA开发一个灵活的框架,整合人类生物监测 (HBM) 数据,暴露组数据集和暴露建模.
- 通过结合暴露,性质,毒性和生物活性信息来支持化学品优先级.
- 通过对特定器官致癌物和常见的化合物进行案例研究来证明框架的实用性.
主要方法:
- 开发了一个由三个模块组成的框架:精心策划的人类暴露组数据库,基于模型的暴露估计,以及毒性/生物活性数据集成.
- 在两个案例研究中应用了框架:优先考虑肝癌原体和确定生物监测中经常检测到的化合物.
- 生成的定量暴露范围,预测的血液度和外部摄入值,以与毒性基准 (例如,AC50) 进行比较.
主要成果:
- 该框架成功地整合了各种数据类型,以支持NGRA.
- 案例研究表明,该框架能够根据人类暴露来优先考虑化学品.
- 结合人类暴露数据被证明会大大影响化学品优先级的结果.
- 产生了量化暴露指标,并与体外毒性数据进行了比较.
结论:
- 开发的框架为嵌入暴露组数据到NGRA提供了一个实用的途径.
- 这种整合加强了化学安全评估的与人类相关的风险评估.
- 该方法提高了化学安全评估的预测能力和人类相关性.
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