Evaluation and Prediction of Pharmacokinetics of PFOA and PFOS in the Monkey and Human Using a PBPK Model

Regul Toxicol Pharmacol. 2011 Feb;59(1):157-75. doi: 10.1016/j.yrtph.2010.12.004.

Abstract

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.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Alkanesulfonates / administration & dosage
  • Alkanesulfonates / pharmacokinetics*
  • Alkanesulfonates / toxicity
  • Alkanesulfonic Acids / pharmacokinetics*
  • Alkylation
  • Animals
  • Caprylates / pharmacokinetics*
  • Carboxylic Acids / administration & dosage
  • Carboxylic Acids / pharmacokinetics*
  • Carboxylic Acids / toxicity
  • Drinking*
  • Female
  • Fluoridation*
  • Fluorides / administration & dosage
  • Fluorides / adverse effects
  • Fluorides / blood
  • Fluorides / pharmacokinetics*
  • Fluorides / toxicity*
  • Fluorocarbons / pharmacokinetics*
  • Germany
  • Half-Life
  • Humans
  • Injections, Intravenous
  • Macaca fascicularis
  • Male
  • Middle Aged
  • Models, Biological*
  • Models, Chemical*
  • Models, Statistical*
  • Nutrition Surveys
  • Ohio
  • Predictive Value of Tests
  • Risk Assessment
  • Sensitivity and Specificity
  • Time Factors
  • United States
  • Water Supply* / standards

Substances

  • Alkanesulfonates
  • Alkanesulfonic Acids
  • Caprylates
  • Carboxylic Acids
  • Fluorocarbons
  • perfluorooctanoic acid
  • perfluorooctane sulfonic acid
  • Fluorides