对于PFOA暴露和风险评估的综合PBPK建模
Achilleas Karakoltzidis1, Spyros P Karakitsios2, Catherine Gabriel1
1Aristotle University of Thessaloniki, Department of Chemical Engineering, Environmental Engineering Laboratory, University Campus, Thessaloniki, 54124, Greece; HERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Balkan Center, Bldg. B, 10th km, Thermi Road, Thessaloniki, 57001, Greece.
和多基基物质 (PFAS) 是持久化学物质. 一个新的药理动力学模型对 perfluorooctanoic 酸 (PFOA) 估计器官度,并证实暴露下降趋势,尽管一些监管限制表明持续的风险.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 药理动力学 药理动力学
背景情况:
- 由于其持久性和生物积累,和多基基物质 (PFAS) 构成公共卫生挑战.
- 现有的人类生物监测 (HBM) 数据显示PFAS存在广泛,需要准确的暴露评估.
- 尿液中PFOA度是不可靠的生物标志物,血清是更一致的指标.
研究的目的:
- 开发一种对 perfluorooctanoic acid (PFOA) 的确定性药理学模型,以估计器官度.
- 使用HBM数据重建体重正常化的PFOA摄入水平.
- 评估目前的PFOA暴露风险与既定监管限制相比.
主要方法:
- 建立了PFOA的决定性药理动力学模型,包括肝脏和脏组织中的积累和循环.
- 利用公开可用的HBM数据集 (HBM4EU,NHANES) 和文献数据,主要是血清测量.
- 基于EFSA,美国和澳大利亚监管限制计算的风险表征比率.
主要成果:
- 该PFOA模型准确地估计了器官度,即使在低暴露水平.
- 估计PFOA暴露水平的下降时间趋势表明监管行动的有效性.
- 风险评估有所不同:EFSA的TWI表明风险很高,而其他限制表明关注程度较低.
结论:
- 基于生理学的药理动力学 (PBPK) 建模和HBM数据对于化学风险评估至关重要.
- 需要不断对PFOA暴露进行重新评估,并确定暴露决定因素.
- 该研究通过提供一个框架来预测内部暴露和验证模型来支持可持续性化学战略 (CSS).
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