{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:18:06Z","timestamp":1790777886979,"version":"4.1.0"},"reference-count":38,"publisher":"American Chemical Society (ACS)","issue":"8","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":654,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Perfluorooctanoic acid (PFOA or C8) has hepatotoxic effects in animals. Cross-sectional epidemiologic studies suggest PFOA is associated with liver injury biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>We estimated associations between modeled historical PFOA exposures and liver injury biomarkers and medically validated liver disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Participants completed surveys during 2008\u20132011 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), \u03b3-glutamyltransferase (GGT) and direct bilirubin, markers of liver toxicity, were obtained from blood samples collected in the C8 Health Project (2005\u20132006). 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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Modeled cumulative serum PFOA was positively associated with ALT levels (p for trend &amp;lt; 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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Citation:<\/jats:title>\n                    <jats:p>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\u20131233;\u2002http:\/\/dx.doi.org\/10.1289\/ehp.1510391<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1289\/ehp.1510391","type":"journal-article","created":{"date-parts":[[2016,3,15]],"date-time":"2016-03-15T11:04:05Z","timestamp":1458039845000},"page":"1227-1233","source":"Crossref","is-referenced-by-count":121,"title":["Modeled Perfluorooctanoic Acid (PFOA) Exposure and Liver Function in a Mid-Ohio Valley Community"],"prefix":"10.1021","volume":"124","author":[{"given":"Lyndsey A.","family":"Darrow","sequence":"first","affiliation":[{"name":"School of Community Health Sciences, University of Nevada, Reno, Reno, Nevada, USA"},{"name":"Department of Epidemiology, and"},{"name":"Department of Environmental Health, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyx C.","family":"Groth","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Winquist","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, and"},{"name":"Department of Environmental Health, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeong-Moo","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, University of California, Davis, Davis, California, USA"},{"name":"School of Social Ecology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Bartell","sequence":"additional","affiliation":[{"name":"Department of Statistics, and"},{"name":"Department of Epidemiology, University of California, Irvine, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Steenland","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, and"},{"name":"Department of Environmental Health, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2016,3,15]]},"reference":[{"issue":"1","key":"2026081810464654500_micit1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1155\/2003\/135859","article-title":"Peroxisomal enzymes and 8-hydroxydeoxyguanosine in rat liver treated with perfluorooctanoic acid.","volume":"19","author":"Abdellatif","year":"2003","journal-title":"Dis Markers"},{"key":"2026081810464654500_micit2","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1289\/ehp.0901252","article-title":"Rate of decline in serum PFOA concentrations after granular activated carbon filtration at two public water systems in Ohio and West Virginia.","volume":"118","author":"Bartell","year":"2010","journal-title":"Environ Health Perspect"},{"issue":"1\u20133","key":"2026081810464654500_micit3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.tox.2011.06.012","article-title":"Multiplicity of nuclear receptor activation by PFOA and PFOS in primary human and rodent hepatocytes.","volume":"288","author":"Bjork","year":"2011","journal-title":"Toxicology"},{"issue":"1","key":"2026081810464654500_micit4","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1093\/toxsci\/69.1.244","article-title":"Toxicity of ammonium perfluorooctanoate in male cynomolgus monkeys after oral dosing for 6 months.","volume":"69","author":"Butenhoff","year":"2002","journal-title":"Toxicol Sci"},{"key":"2026081810464654500_micit5","unstructured":"C8 Science Panel\n          . 2012. 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