Modeled Perfluorooctanoic Acid (PFOA) Exposure and Liver Function in a Mid-Ohio Valley Community

Environ Health Perspect. 2016 Aug;124(8):1227-33. doi: 10.1289/ehp.1510391. Epub 2016 Mar 15.


Background: Perfluorooctanoic acid (PFOA or C8) has hepatotoxic effects in animals. Cross-sectional epidemiologic studies suggest PFOA is associated with liver injury biomarkers.

Objectives: We estimated associations between modeled historical PFOA exposures and liver injury biomarkers and medically validated liver disease.

Methods: Participants completed surveys during 2008-2011 reporting demographic, medical, and residential history information. Self-reported liver disease, including hepatitis, fatty liver, enlarged liver and cirrhosis, was validated with healthcare providers. Alanine aminotransferase (ALT), γ-glutamyltransferase (GGT) and direct bilirubin, markers of liver toxicity, were obtained from blood samples collected in the C8 Health Project (2005-2006). Historically modeled PFOA exposure, estimated using environmental fate and transport models and participant residential histories, was analyzed in relation to liver biomarkers (n = 30,723, including 1,892 workers) and liver disease (n = 32,254, including 3,713 workers).

Results: Modeled cumulative serum PFOA was positively associated with ALT levels (p for trend < 0.0001), indicating possible liver toxicity. An increase from the first to the fifth quintile of cumulative PFOA exposure was associated with a 6% increase in ALT levels (95% CI: 4, 8%) and a 16% increased odds of having above-normal ALT (95% CI: odds ratio: 1.02, 1.33%). There was no indication of association with either elevated direct bilirubin or GGT; however, PFOA was associated with decreased direct bilirubin. We observed no evidence of an effect of cumulative exposure (with or without a 10-year lag) on all liver disease (n = 647 cases), nor on enlarged liver, fatty liver, and cirrhosis only (n = 427 cases).

Conclusion: Results are consistent with previous cross-sectional studies showing association between PFOA and ALT, a marker of hepatocellular damage. We did not observe evidence that PFOA increases the risk of clinically diagnosed liver disease.

Citation: Darrow LA, Groth AC, Winquist A, Shin HM, Bartell SM, Steenland K. 2016. Modeled perfluorooctanoic acid (PFOA) exposure and liver function in a Mid-Ohio Valley community. Environ Health Perspect 124:1227-1233;

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / metabolism
  • Biomarkers / metabolism
  • Caprylates / blood
  • Caprylates / toxicity*
  • Cross-Sectional Studies
  • Environmental Exposure / statistics & numerical data*
  • Environmental Pollutants / metabolism
  • Environmental Pollutants / toxicity*
  • Female
  • Fluorocarbons / blood
  • Fluorocarbons / toxicity*
  • Humans
  • Liver / metabolism*
  • Male
  • Ohio
  • gamma-Glutamyltransferase / metabolism


  • Biomarkers
  • Caprylates
  • Environmental Pollutants
  • Fluorocarbons
  • perfluorooctanoic acid
  • gamma-Glutamyltransferase
  • Alanine Transaminase