Perfluorooctanoic acid-induced hepatic toxicity following 21-day oral exposure in mice

Arch Toxicol. 2008 Apr;82(4):239-46. doi: 10.1007/s00204-007-0246-x. Epub 2007 Sep 14.


Perfluorooctanoic acid (PFOA) is a member of the perfluoroalkyl acids that have wide commercial applications and is a widespread pollutant of toxicological importance that has been detected in environmental matrices. The NOAEL and LOAEL of PFOA in rodent were reported 1 and 10 ppm, respectively. The current study characterizes the hepatic toxicities of PFOA in mice. Male ICR mice were exposed continuously to 0, 2, 10, 50 and 250 ppm of PFOA in drinking water for 21 days. Food and water consumption decreased in mice exposed to 250 ppm of PFOA. Mean body weight gain was reduced in mice exposed to 50 and 250 ppm of PFOA. The size and relative weight of the liver increased dose-dependently in PFOA-treated mice. Serum enzyme activities, alanine aminotransferase and aspartate aminotransferase, increased in mice exposed to PFOA in a dose-dependent manner. In the histopathological evaluation, the liver of PFOA-treated mice showed remarkable hepatocytomegaly and acidophilic cytoplasm. At the high doses of PFOA, diffuse hepatic damage by multifocal coagualation and liquefaction necrosis were noted. In contrast to the remarkable change of liver, the kidney had little change. The size and relative weights of the kidney, biomarkers of kidney damage (blood urea nitrogen, creatinine), and histopathological changes had no differences between PFOA-untreated and PFOA-treated mice. In conclusion, our results demonstrate that PFOA causes a toxic effect on the liver but not to the kidney.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caprylates / toxicity*
  • Caspase 3 / metabolism
  • Chemical and Drug Induced Liver Injury / enzymology
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / immunology
  • Chemical and Drug Induced Liver Injury / pathology
  • Cytokines / biosynthesis
  • Dose-Response Relationship, Drug
  • Fluorocarbons / toxicity*
  • Liver / drug effects
  • Liver / enzymology
  • Liver / immunology
  • Liver / pathology
  • Liver Function Tests
  • Male
  • Mice
  • Mice, Inbred ICR
  • Organ Size / drug effects
  • Toxicity Tests, Chronic


  • Caprylates
  • Cytokines
  • Fluorocarbons
  • perfluorooctanoic acid
  • Caspase 3