Evaluation of placental and lactational pharmacokinetics of PFOA and PFOS in the pregnant, lactating, fetal and neonatal rat using a physiologically based pharmacokinetic model

Reprod Toxicol. 2012 Jul;33(4):468-490. doi: 10.1016/j.reprotox.2011.07.003. Epub 2011 Aug 18.

Abstract

Perfluoroalkyl carboxylates and sulfonates (PFAAs) have many consumer and industrial applications. Developmental toxicity studies in animals have raised concern about potential developmental effects of PFOA and PFOS in humans. We have developed PBPK models for PFAAs in the rat to help define a relationship between external dose, internal tissue concentrations, and observed adverse effects, and to understand how physiological changes that occur during gestation and lactation affect tissue distribution of PFAAs in the mother, fetus, and neonate. The models developed here expand upon a PBPK model for PFAAs in the adult female rat, and are consistent with available PK data. These models, along with the adult rat PFAA models, published in the companion paper, will help address concerns about possible health effects due to PFAA exposure in the fetus and neonate and will be useful in comparing PK across life stages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Alkanesulfonic Acids / blood
  • Alkanesulfonic Acids / pharmacokinetics*
  • Alkanesulfonic Acids / toxicity
  • Animals
  • Animals, Newborn
  • Body Weight / physiology
  • Caprylates / blood
  • Caprylates / pharmacokinetics*
  • Caprylates / toxicity
  • Computer Simulation
  • Dose-Response Relationship, Drug
  • Female
  • Fetal Blood / chemistry
  • Fluorocarbons / blood
  • Fluorocarbons / pharmacokinetics*
  • Fluorocarbons / toxicity
  • Gestational Age
  • Lactation* / metabolism
  • Liver / embryology
  • Liver / metabolism
  • Maternal Exposure* / adverse effects
  • Maternal-Fetal Exchange*
  • Milk / chemistry
  • Models, Biological*
  • Placenta / metabolism*
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Regional Blood Flow / physiology
  • Tissue Distribution

Substances

  • Alkanesulfonic Acids
  • Caprylates
  • Fluorocarbons
  • perfluorooctanoic acid
  • perfluorooctane sulfonic acid