Prenatal perfluorooctanoic acid exposure in CD-1 mice: low-dose developmental effects and internal dosimetry

Toxicol Sci. 2011 Jul;122(1):134-45. doi: 10.1093/toxsci/kfr076. Epub 2011 Apr 11.

Abstract

Perfluorooctanoic acid (PFOA) is an environmental contaminant that causes adverse developmental effects in laboratory animals. To investigate the low-dose effects of PFOA on offspring, timed-pregnant CD-1 mice were gavage dosed with PFOA for all or half of gestation. In the full-gestation study, mice were administered 0, 0.3, 1.0, and 3.0 mg PFOA/kg body weight (BW)/day from gestation days (GD) 1-17. In the late-gestation study, mice were administered 0, 0.01, 0.1, and 1.0 mg PFOA/kg BW/day from GD 10-17. Exposure to PFOA significantly (p < 0.05) increased offspring relative liver weights in all treatment groups in the full-gestation study and in the 1.0 mg PFOA/kg group in the late-gestation study. In both studies, the offspring of all PFOA-treated dams exhibited significantly stunted mammary epithelial growth as assessed by developmental scoring. At postnatal day 21, mammary glands from the 1.0 mg/kg GD 10-17 group had significantly less longitudinal epithelial growth and fewer terminal end buds compared with controls (p < 0.05). Evaluation of internal dosimetry in offspring revealed that PFOA concentrations remained elevated in liver and serum for up to 6 weeks and that brain concentrations were low and undetectable after 4 weeks. These data indicate that PFOA-induced effects on mammary tissue (1) occur at lower doses than effects on liver weight in CD-1 mice, an observation that may be strain specific, and (2) persist until 12 weeks of age following full-gestational exposure. Due to the low-dose sensitivity of mammary glands to PFOA in CD-1 mice, a no observable adverse effect level for mammary developmental delays was not identified in these studies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Body Weight / drug effects
  • Caprylates / blood
  • Caprylates / toxicity*
  • Dose-Response Relationship, Drug
  • Female
  • Fluorocarbons / blood
  • Fluorocarbons / toxicity*
  • Gestational Age
  • Liver / drug effects
  • Male
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / pathology
  • Maternal Exposure / adverse effects*
  • Mice
  • Mice, Inbred Strains
  • No-Observed-Adverse-Effect Level
  • Organ Size / drug effects
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Sensitivity and Specificity

Substances

  • Caprylates
  • Fluorocarbons
  • perfluorooctanoic acid