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Physiologically based pharmacokinetic modeling of human exposure to perfluorooctanoic acid suggests historical non drinking-water exposures are important for predicting current serum concentrations

机译：人体全氟辛酸暴露的基于生理学的药代动力学模型表明非饮用水的历史暴露对于预测当前的血清浓度非常重要

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Manufacturing of perfluorooctanoic acid (PFOA), a synthetic chemical with a long half-life in humans, peaked between 1970 and 2002, and has since diminished. In the United States, PFOA is detected in the blood of >99% of people tested, but serum concentrations have decreased since 1999. Much is known about exposure to PFOA in drinking water; however, the impact of non-drinking water PFOA exposure on serum PFOA concentrations is not well characterized.The objective of this research is to apply physiologically based pharmacokinetic (PBPK) modeling and Monte Carlo analysis to evaluate the impact of historic non-drinking water PFOA exposure on serum PFOA concentrations.In vitro to in vivo extrapolation was utilized to inform descriptions of PFOA transport in the kidney. Monte Carlo simulations were incorporated to evaluate factors that account for the large inter-individual variability of serum PFOA concentrations measured in individuals from North Alabama in 2010 and 2016, and the Mid-Ohio River Valley between 2005 and 2008.Predicted serum PFOA concentrations were within two-fold of experimental data. With incorporation of Monte Carlo simulations, the model successfully tracked the large variability of serum PFOA concentrations measured in populations from the Mid-Ohio River Valley. Simulation of exposure in a population of 45 adults from North Alabama successfully predicted 98% of individual serum PFOA concentrations measured in 2010 and 2016, respectively, when non-drinking water ingestion of PFOA exposure was included.Variation in serum PFOA concentrations may be due to inter-individual variability in the disposition of PFOA and potentially elevated historical non-drinking water exposures.
机译：全氟辛酸（PFOA）的生产是一种在人类中具有较长半衰期的合成化学品，在1970年至2002年间达到了顶峰，此后一直在减少。在美国，超过99％的被测者的血液中检测到PFOA，但自1999年以来血清浓度有所降低。然而，非饮用水PFOA暴露对血清PFOA浓度的影响尚不十分清楚。本研究的目的是应用基于生理的药代动力学（PBPK）模型和Monte Carlo分析来评估历史性非饮用水PFOA的影响。体外至体内外推法可用于描述PFOA在肾脏中的转运。蒙特卡罗模拟被纳入评估因素，这些因素解释了2010年和2016年在阿拉巴马州北部以及2005年至2008年在俄亥俄河谷地区个体测得的血清PFOA浓度的较大个体间差异。实验数据的两倍。结合蒙特卡罗模拟，该模型成功地追踪了俄亥俄州中河谷地区人群中测得的血清PFOA浓度的巨大变化。在阿拉巴马州北部的45名成年人中进行的暴露模拟研究成功地预测了在2010年和2016年测得的98％的个体血清PFOA浓度（包括不饮水摄入的PFOA暴露）。血清PFOA浓度的变化可能是由于PFOA处置的个体差异和历史性非饮水暴露量的潜在增加。

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