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3749173 
Journal Article 
Modeled perfluorooctanoic acid (PFOA) exposure and liver function in a mid-Ohio valley community 
Darrow, LA; Groth, AC; Winquist, A; Shin, HM; Bartell, SM; Steenland, K 
2016 
Yes 
Environmental Health Perspectives
ISSN: 0091-6765
EISSN: 1552-9924 
124 
1227-1233 
English 
is supplemented by 3986320 Supplemental material:
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; http://dx.doi.org/10.1289/ehp.1510391. 
PFAS
• Additional PFAS (formerly XAgency)
     Literature Search November 2019
          Other Sources
               ATSDR
     Screened Studies
          Excluded
               Exclude (TIAB)
• Expanded PFAS SEM (formerly PFAS 430)
     Litsearch: September 2019
          PubMed
     Not prioritized for screening
     Potassium perfluorooctanoate
     Sodium perfluorooctanoate
• ^Per- and Polyfluoroalkyl Substances (PFAS)
     PFOA (335-67-1) and PFOS (1763-23-1)
          Literature Search – Adverse outcome pathway (2015-present)
               Pubmed
               WOS
• PFAS 150
     Literature Search August 2019
          PubMed
          Web of Science
          Other sources
               Reference list review of included studies
     Not prioritized for screening
     Ammonium perfluorooctanoate
     Perfluorooctanoic acid
• PFAS Universe
     Data Source
          Web of Science
          Pubmed
          Screened Studies
               Excluded
                    Exclude (TIAB)
     Ammonium perfluorooctanoate
     Perfluorooctanoate
     Perfluorooctanoic acid
• PFHxS
     Additional references submitted during ERG review
OW - HHRAB
• PFOA (335-67-1) and PFOS (1763-23-1)
     Literature Search – Adverse outcome pathway (2015-present)
          Pubmed
          WOS
     Screening Results
          Human/Epi studies
               Liver tox
     Literature Search Update (2013-2019)
          PubMed
          WOS
• PFOA and PFOS OW MCLG Approaches
     Cited in White Papers