Neonatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) causes neurobehavioural defects in adult mice

Neurotoxicology. 2008 Jan;29(1):160-9. doi: 10.1016/j.neuro.2007.10.008. Epub 2007 Nov 1.

Abstract

Perfluorinated compounds (PFCs) are found in applications such oil/water repellents for clothing fabrics, carpets, food packaging, lubricants, surfactants and fire extinguishers. PFCs are persistent in the environment. They have been found in humans and in wildlife. We reported earlier that persistent organic pollutants (POPs), such as DDT, PCBs and BFRs, caused developmental neurotoxic defects in mice, manifested as persistent aberrations in spontaneous behaviour, habituation capability, learning and memory, and changes in the cholinergic system in adults, when mice were exposed during a critical period of neonatal brain development. The present study was conducted to see whether PFCs can cause similar developmental neurotoxic effects as earlier observed for POPs as PCBs and PBDEs. NMRI male mice were exposed to a single-oral dose, either 1.4 or 21 micromol/kg body weight of PFOS (0.75 or 11.3 mg), PFOA (0.58 or 8.70 mg), or PFDA (0.72 or 10.8 mg), via a metal gastric-tube at the age of 10 days. The control animals received in the same manner 10 ml/kg body weight of the 20% fat emulsion vehicle. Spontaneous behaviour (locomotion, rearing, and total activity), and habituation were observed in 2- and 4-month-old mice. The susceptibility of the cholinergic system was explored in a nicotine-induced spontaneous behaviour test in 4-month-old mice. Deranged spontaneous behaviour was observed in mice exposed to PFOS and PFOA, manifested as reduced and/or lack of habituation and hyperactivity in adult mice. These effects were also seen to worse with age. Neonatal exposure to PFOS and PFOA affected the cholinergic system, manifested as a hypoactive response to nicotine, compared to a hyperactive response to nicotine in controls. These developmental neurotoxic effects are similar to those we reported earlier for PCBs and PBDEs. This suggests that PFOS and PFOA be included in the group of POPs known to be developmental neurotoxicants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkanesulfonic Acids*
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Behavior, Animal / drug effects
  • Brain Diseases / chemically induced*
  • Brain Diseases / physiopathology
  • Caprylates*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Exploratory Behavior / drug effects
  • Female
  • Fluorocarbons*
  • Locomotion / drug effects
  • Male
  • Maze Learning / drug effects
  • Mental Disorders / chemically induced*
  • Mental Disorders / physiopathology
  • Mice
  • Nicotine / pharmacology
  • Nicotinic Agonists / pharmacology
  • Pregnancy
  • Time Factors

Substances

  • Alkanesulfonic Acids
  • Caprylates
  • Fluorocarbons
  • Nicotinic Agonists
  • Nicotine
  • perfluorooctanoic acid
  • perfluorooctane sulfonic acid