来自老鼠的化聚甲基乙烯硫酸盐的生理学基础毒动力学模型的开发和人类推断
Jing Zhang1,2, Huihui Bao2, Wen-Hui Zhao1
1Joint International Research Laboratory of Environment and Health, Ministry of Education, Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
化聚甲基乙硫酸盐 (F-53B) 的生理基础毒动力学 (PBTK) 模型在老鼠身上开发,并推断到人类身上. 这些模型改善了对一般成人群体F-53B暴露的风险评估.
科学领域:
- 环境化学环境化学
- 毒理学 毒理学 毒理学
- 药理动力学 药理动力学
背景情况:
- 化多醇乙烯硫酸盐 (F-53B) 是遗留PFAS的替代品,具有环境持久性和生物积累风险.
- 对F-53B的有限毒动力学数据阻碍了全面的风险评估.
- F-53B,包括 6:2 Cl-PFESA和 8:2 Cl-PFESA,在环境和人类中被检测到.
研究的目的:
- 在老鼠中开发基于生理学的毒动力学 (PBTK) 模型,用于 6:2 Cl-PFESA 和 8:2 Cl-PFESA.
- 抽出大鼠PBTK模型来预测F-53B的人类毒动力学.
- 加强对F-53B暴露的定量风险评估.
主要方法:
- 给雄性大鼠单次口服和静脉注射F-53B剂量.
- 在生物样本中使用超高性能液态染色体质谱学量化的F-53B度.
- 开发并验证了6:2 Cl-PFESA和8:2 Cl-PFESA的PBTK模型,并推断到人类.
主要成果:
- 6:2 Cl-PFESA 主要分布在肝脏和血中; 8:2 Cl-PFESA 分布在肝脏和肺部.
- PBTK模型准确地预测了F-53B度 (100%用于6:2Cl-PFESA,92%用于8:2Cl-PFESA).
- 通过使用生物监测数据来验证额外推算的人类模型.
结论:
- 在老鼠和人类中,已建立F-53B (6:2 Cl-PFESA和 8:2 Cl-PFESA) 的PBTK模型.
- 模型为F-53B.的定量风险评估提供了坚实的框架.
- 更好地了解F-53B毒动力学有助于评估对一般成年人群的风险.
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