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

Abstract

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 ofmore » 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. - Highlights: • PBPK modeling and Monte Carlo analysis applied to evaluate historic PFOA exposure. • In vitro to in vivo extrapolation informed description of PFOA transport in kidney. • Model predicted large range of serum PFOA concentrations in two communities. • Variation in serum concentrations may be due to historic non-drinking water exposure.« less

Authors:
 [1];  [2];  [3];  [4];  [2]
  1. Division of Community Health Investigations, Agency for Toxic Substances and Disease Registry, Atlanta, GA (United States)
  2. (United States)
  3. National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR (United States)
  4. Interdisciplinary Toxicology Program, University of Georgia, Athens, GA (United States)
Publication Date:
OSTI Identifier:
22722909
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 330; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; COMPUTERIZED SIMULATION; CONCENTRATION RATIO; DRINKING WATER; ECOLOGICAL CONCENTRATION; EXPERIMENTAL DATA; FLUORINE COMPOUNDS; MONTE CARLO METHOD; PARTICLE TRACKS

Citation Formats

Worley, Rachel Rogers, E-mail: RWorley@cdc.gov, Interdisciplinary Toxicology Program, University of Georgia, Athens, GA, Yang, Xiaoxia, Fisher, Jeffrey, and National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR. Physiologically based pharmacokinetic modeling of human exposure to perfluorooctanoic acid suggests historical non drinking-water exposures are important for predicting current serum concentrations. United States: N. p., 2017. Web. doi:10.1016/J.TAAP.2017.07.001.
Worley, Rachel Rogers, E-mail: RWorley@cdc.gov, Interdisciplinary Toxicology Program, University of Georgia, Athens, GA, Yang, Xiaoxia, Fisher, Jeffrey, & National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR. Physiologically based pharmacokinetic modeling of human exposure to perfluorooctanoic acid suggests historical non drinking-water exposures are important for predicting current serum concentrations. United States. doi:10.1016/J.TAAP.2017.07.001.
Worley, Rachel Rogers, E-mail: RWorley@cdc.gov, Interdisciplinary Toxicology Program, University of Georgia, Athens, GA, Yang, Xiaoxia, Fisher, Jeffrey, and National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR. Fri . "Physiologically based pharmacokinetic modeling of human exposure to perfluorooctanoic acid suggests historical non drinking-water exposures are important for predicting current serum concentrations". United States. doi:10.1016/J.TAAP.2017.07.001.
@article{osti_22722909,
title = {Physiologically based pharmacokinetic modeling of human exposure to perfluorooctanoic acid suggests historical non drinking-water exposures are important for predicting current serum concentrations},
author = {Worley, Rachel Rogers, E-mail: RWorley@cdc.gov and Interdisciplinary Toxicology Program, University of Georgia, Athens, GA and Yang, Xiaoxia and Fisher, Jeffrey and National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR},
abstractNote = {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. - Highlights: • PBPK modeling and Monte Carlo analysis applied to evaluate historic PFOA exposure. • In vitro to in vivo extrapolation informed description of PFOA transport in kidney. • Model predicted large range of serum PFOA concentrations in two communities. • Variation in serum concentrations may be due to historic non-drinking water exposure.},
doi = {10.1016/J.TAAP.2017.07.001},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = ,
volume = 330,
place = {United States},
year = {2017},
month = {9}
}