Center for Human Health Assessment, Hamner Institutes for Health Sciences, 6 Davis Drive, P.O. Box 12137, Research Triangle Park, NC 27709, United States.
Regul Toxicol Pharmacol. 2011 Feb;59(1):157-75. doi: 10.1016/j.yrtph.2010.12.004.
Perfluoroalkyl acid carboxylates and sulfonates (PFAAs) have many consumer and industrial applications. The persistence and widespread distribution of these compounds in humans have brought them under intense scrutiny. Limited pharmacokinetic data is available in humans; however, human data exists for two communities with drinking water contaminated by PFAAs. Also, there is toxicological and pharmacokinetic data for monkeys, which can be quite useful for cross-species extrapolation to humans. The goal of this research was to develop a physiologically-based pharmacokinetic (PBPK) model for PFOA and PFOS for monkeys and then scale this model to humans in order to describe available human drinking water data. The monkey model simulations were consistent with available PK data for monkeys. The monkey model was then extrapolated to the human and then used to successfully simulate the data collected from residents of two communities exposed to PFOA in drinking water. Human PFOS data is minimal; however, using the half-life estimated from occupational exposure, our model exhibits reasonable agreement with the available human serum PFOS data. It is envisioned that our PBPK model will be useful in supporting human health risk assessments for PFOA and PFOS by aiding in understanding of human pharmacokinetics.
全氟烷基酸羧酸酯和磺酸盐（PFAAs）在消费者和工业中有广泛的应用。这些化合物在人类体内的持久性和广泛分布使它们受到了严格的审查。目前人类的药代动力学数据有限，但对于饮用水受到 PFAAs 污染的两个社区，已有人类数据。此外，猴子的毒理学和药代动力学数据也存在，这些数据对于跨物种外推到人类非常有用。本研究的目的是为猴子开发一种基于生理的药代动力学（PBPK）模型，用于描述现有的人类饮用水数据。猴子模型的模拟结果与猴子的可用 PK 数据一致。然后，将猴子模型外推到人类，并用于成功模拟暴露于饮用水中 PFOA 的两个社区居民的收集数据。人类 PFOS 数据非常有限；然而，使用从职业暴露中估计的半衰期，我们的模型与现有的人类血清 PFOS 数据具有合理的一致性。预计我们的 PBPK 模型将有助于理解人类的药代动力学，从而为 PFOA 和 PFOS 的人类健康风险评估提供支持。
