{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:02:31Z","timestamp":1791482551274,"version":"4.3.4"},"reference-count":35,"publisher":"American Chemical Society (ACS)","issue":"5","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":2160,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) persist in the environment and are found in relatively high concentrations in animal livers. Studies in humans have reported inconsistent associations between PFOA and liver enzymes.<\/jats:p>\n                  <jats:p>Objectives: We examined the cross-sectional association between serum PFOA and PFOS concentrations with markers of liver function in adults.<\/jats:p>\n                  <jats:p>Methods: The C8 Health Project collected data on 69,030 persons; of these, a total of 47,092 adults were included in the present analysis. Linear regression models were fitted for natural log (ln)-transformed values of alanine transaminase (ALT), \u03b3-glutamyltransferase (GGT), and direct bilirubin on PFOA, PFOS, and potential confounders. Logistic regression models were fitted comparing deciles of PFOA or PFOS in relation to high biomarker levels. A multilevel analysis comparing the evidence for association of PFOA with liver function at the individual level within water districts to that at the population level between water districts was also performed.<\/jats:p>\n                  <jats:p>Results: ln-PFOA and ln-PFOS were associated with ln-ALT in linear regression models [PFOA: coefficient, 0.022; 95% confidence interval (CI): 0.018, 0.025; PFOS: coefficient, 0.020; 95% CI: 0.014, 0.026] and with raised ALT in logistic regression models [with a steady increase in the odds ratio (OR) estimates across deciles of PFOA and PFOS; PFOA: OR = 1.10; 95% CI: 1.07, 1.13; PFOS: OR = 1.13; 95% CI: 1.07, 1.18]. There was less consistent evidence of an association of PFOA and GGT or bilirubin. The relationship with bilirubin appears to rise at low levels of PFOA and to fall again at higher levels.<\/jats:p>\n                  <jats:p>Conclusions: These results show a positive association between PFOA and PFOS concentrations and serum ALT level, a marker of hepatocellular damage.<\/jats:p>","DOI":"10.1289\/ehp.1104436","type":"journal-article","created":{"date-parts":[[2012,1,30]],"date-time":"2012-01-30T10:34:34Z","timestamp":1327919674000},"page":"655-660","source":"Crossref","is-referenced-by-count":276,"title":["Serum Perfluorooctanoate (PFOA) and Perfluorooctane Sulfonate (PFOS) Concentrations and Liver Function Biomarkers in a Population with Elevated PFOA Exposure"],"prefix":"10.1021","volume":"120","author":[{"given":"Valentina","family":"Gallo","sequence":"first","affiliation":[{"name":"Social and Environmental Health Research, London School of Hygiene and Tropical Medicine, London, United Kingdom"},{"name":"School of Public Health, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Leonardi","sequence":"additional","affiliation":[{"name":"Social and Environmental Health Research, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Genser","sequence":"additional","affiliation":[{"name":"Mannheim Institute of Public Health, Social and Preventive Medicine, University of Heidelberg, Heidelberg, Germany"},{"name":"Instituto de Sa\u00fade Coletiva, Federal University of Bahia, Salvador, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Jose","family":"Lopez-Espinosa","sequence":"additional","affiliation":[{"name":"Social and Environmental Health Research, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie J.","family":"Frisbee","sequence":"additional","affiliation":[{"name":"Department of Community Medicine and Center for Cardiovascular and Respiratory Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Social and Environmental Health Research, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan M.","family":"Ducatman","sequence":"additional","affiliation":[{"name":"Department of Community Medicine, West Virginia University School of Medicine, Morgantown, West Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Fletcher","sequence":"additional","affiliation":[{"name":"Social and Environmental Health Research, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2012,1,30]]},"reference":[{"key":"2026080314063578900_micit1","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"},{"key":"2026080314063578900_micit2","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1111\/j.1572-0241.2003.07486.x","article-title":"The prevalence and etiology of elevated aminotransferase levels in the United States.","volume":"98","author":"Clark","year":"2003","journal-title":"Am J Gastroenterol"},{"key":"2026080314063578900_micit3","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1097\/JOM.0b013e3181965d80","article-title":"Thirty years of medical surveillance in perfluooctanoic acid production workers.","volume":"51","author":"Costa","year":"2009","journal-title":"J Occup Environ Med"},{"key":"2026080314063578900_micit4","doi-asserted-by":"crossref","first-page":"215","DOI":"10.2307\/2089857","article-title":"A technique for analyzing the effects of group composition.","volume":"26","author":"Davis","year":"1961","journal-title":"Am Social Rev"},{"key":"2026080314063578900_micit5","first-page":"179","article-title":"Perfluorinated substances in human food and other sources of human exposure.","volume":"208","author":"D\u2019Hollander","year":"2010","journal-title":"Rev Environ Contam Toxicol"},{"key":"2026080314063578900_micit6","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1097\/01.jom.0000232486.07658.74","article-title":"Community exposure to perfluorooctanoate: relationships between serum concentrations and exposure sources.","volume":"48","author":"Emmett","year":"2006","journal-title":"J Occup Environ Med"},{"key":"2026080314063578900_micit7","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1289\/ehp.0800379","article-title":"The C8 health project: design, methods, and participants.","volume":"117","author":"Frisbee","year":"2009","journal-title":"Environ Health Perspect"},{"key":"2026080314063578900_micit8","doi-asserted-by":"publisher","first-page":"e1001117","DOI":"10.1371\/journal.pmed.1001117","article-title":"STrengthening the Reporting of OBservational studies in Epidemiology\u2014Molecular Epidemiology (STROBE-ME): an extension of the STROBE statement.","volume":"8","author":"Gallo","year":"2011","journal-title":"PLoS Med"},{"key":"2026080314063578900_micit9","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.envint.2010.08.001","article-title":"Perfluoroalkyl compounds in dust from Asian, Australian, European, and North American homes and UK cars, classrooms, and offices.","volume":"37","author":"Goosey","year":"2011","journal-title":"Environ Int"},{"key":"2026080314063578900_micit10","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1053\/j.gastro.2004.12.004","article-title":"Contribution of metabolic factors to alanine aminotransferase activity in persons with other causes of liver disease.","volume":"128","author":"Ioannou","year":"2005","journal-title":"Gastroenterology"},{"issue":"19","key":"2026080314063578900_micit11","doi-asserted-by":"crossref","first-page":"8037","DOI":"10.1021\/es1043613","article-title":"Trends in exposure to polyfluoroalkyl chemicals in the U.S. population: 1999\u20132008.","volume":"45","author":"Kato","year":"2011","journal-title":"Environ Sci Technol"},{"key":"2026080314063578900_micit12","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.envpol.2010.09.008","article-title":"Distribution of perfluorochemicals between sera and milk from the same mothers and implications for prenatal and postnatal exposures.","volume":"159","author":"Kim","year":"2011","journal-title":"Environ Pollut"},{"key":"2026080314063578900_micit13","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1056\/NEJMcpc049016","article-title":"Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Laboratory reference values.","volume":"351","author":"Kratz","year":"2004","journal-title":"N Engl J Med"},{"key":"2026080314063578900_micit14","doi-asserted-by":"crossref","first-page":"3698","DOI":"10.1021\/es040332u","article-title":"Automated solid-phase extraction and measurement of perfluorinated organic acids and amides in human serum and milk.","volume":"38","author":"Kuklenyik","year":"2004","journal-title":"Environ Sci Technol"},{"key":"2026080314063578900_micit15","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1093\/toxsci\/kfm128","article-title":"Perfluoroalkyl acids: a review of monitoring and toxico-logical findings.","volume":"99","author":"Lau","year":"2007","journal-title":"Toxicol Sci"},{"key":"2026080314063578900_micit16","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1093\/ajcn\/79.4.600","article-title":"Association between serum \u03b3-glutamyltransferase and dietary factors: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.","volume":"79","author":"Lee","year":"2004","journal-title":"Am J Clin Nutr"},{"key":"2026080314063578900_micit17","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1038\/ajg.2009.707","article-title":"Investigation of the associations between low-dose serum perfluorinated chemicals and liver enzymes in US adults.","volume":"105","author":"Lin","year":"2010","journal-title":"Am J Gastroenterol"},{"key":"2026080314063578900_micit18","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: insulin resistance and \u03b2-cell function from fasting plasma glucose and insulin concentrations in man.","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"2026080314063578900_micit19","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s00420-007-0213-0","article-title":"Assessment of lipid, hepatic, and thyroid parameters with serum perfluorooctanoate (PFOA) concentrations in fluorochemical production workers.","volume":"81","author":"Olsen","year":"2007","journal-title":"Int Arch Occup Environ Health"},{"key":"2026080314063578900_micit20","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/173907","article-title":"PRIC295, a nuclear receptor coactivator, identified from PPAR\u03b1-interacting cofactor complex.","volume":"173907","author":"Pyper","year":"2010","journal-title":"PPAR Res"},{"key":"2026080314063578900_micit21","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1016\/j.intimp.2010.08.009","article-title":"Dietary exposure to perfluorooctanoate or perfluoro-octane sulfonate induces hypertrophy in centrilobular hepato-cytes and alters the hepatic immune status in mice.","volume":"10","author":"Qazi","year":"2010","journal-title":"Int Immunopharmacol"},{"key":"2026080314063578900_micit22","doi-asserted-by":"publisher","first-page":"e6796","DOI":"10.1371\/journal.pone.0006796","article-title":"Comparative analysis of gene regulation by the transcription factor PPAR\u03b1 between mouse and human.","volume":"4","author":"Rakhshandehroo","year":"2009","journal-title":"PLoS One"},{"key":"2026080314063578900_micit23","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.reprotox.2008.12.011","article-title":"Evidence for the involvement of xenobiotic-responsive nuclear receptors in transcriptional effects upon perfluoroalkyl acid exposure in diverse species.","volume":"27","author":"Ren","year":"2009","journal-title":"Reprod Toxicol"},{"key":"2026080314063578900_micit24","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1053\/gast.2003.50004","article-title":"Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States.","volume":"124","author":"Ruhl","year":"2003","journal-title":"Gastroenterology"},{"key":"2026080314063578900_micit25","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1097\/JOM.0b013e318156eca3","article-title":"Cross-sectional study of lipids and liver enzymes related to a serum biomarker of exposure (ammonium perfluorooctanoate or APFO) as part of a general health survey in a cohort of occupationally exposed workers.","volume":"49","author":"Sakr","year":"2007","journal-title":"J Occup Environ Med"},{"key":"2026080314063578900_micit26","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1097\/JOM.0b013e318124a93f","article-title":"Longitudinal study of serum lipids and liver enzymes in workers with occupational exposure to ammonium perfluoro-octanoate.","volume":"49","author":"Sakr","year":"2007","journal-title":"J Occup Environ Med"},{"key":"2026080314063578900_micit27","first-page":"718","article-title":"IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. International Federation of Clinical Chemistry and Laboratory Medicine. Part 4. Reference procedure for the measurement of catalytic concentration of alanine aminotransferase.","volume":"40","author":"Schumann","year":"2002","journal-title":"Clin Chem Lab Med"},{"key":"2026080314063578900_micit28","first-page":"734","article-title":"IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. International Federation of Clinical Chemistry and Laboratory Medicine. Part 6. Reference procedure for the measurement of catalytic concentration of gamma-glutamyltransferase.","volume":"40","author":"Schumann","year":"2002","journal-title":"Clin Chem Lab Med"},{"key":"2026080314063578900_micit29","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1542\/peds.113.6.1776","article-title":"Bilirubin benefits: cellular protection by a biliverdin reductase antioxidant cycle.","volume":"113","author":"Sedlak","year":"2004","journal-title":"Pediatrics"},{"key":"2026080314063578900_micit30","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1289\/ehp.1103729","article-title":"Retrospective exposure estimation and predicted versus observed serum perfluorooctanoic acid concentrations for participants in the C8 Health Project.","volume":"119","author":"Shin","year":"2011","journal-title":"Environ Health Perspect"},{"key":"2026080314063578900_micit31","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1289\/ehp.0800294","article-title":"Predictors of PFOA levels in community surrounding a chemical plant.","volume":"117","author":"Steenland","year":"2009","journal-title":"Environ Health Perspect"},{"key":"2026080314063578900_micit32","doi-asserted-by":"crossref","first-page":"7642","DOI":"10.1021\/es061513u","article-title":"Perfluorooctanesulfonate and related fluorochemicals in albatrosses, elephant seals, penguins, and polar skuas from the Southern Ocean.","volume":"40","author":"Tao","year":"2006","journal-title":"Environ Sci Technol"},{"key":"2026080314063578900_micit33","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1080\/20014091084227","article-title":"Gamma glutamyl transferase.","volume":"38","author":"Whitfield","year":"2001","journal-title":"Crit Rev Clin Lab Sci"},{"key":"2026080314063578900_micit34","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1177\/0192623308318216","article-title":"Comparative hepatic effects of perfluorooctanoic acid and WY 14,643 in PPAR-\u03b1 knockout and wild-type mice.","volume":"36","author":"Wolf","year":"2008","journal-title":"Toxicol Pathol"},{"key":"2026080314063578900_micit35","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1093\/toxsci\/kfm206","article-title":"The PPAR\u03b1-humanized mouse: a model to investigate species differences in liver toxicity mediated by PPAR\u03b1.","volume":"101","author":"Yang","year":"2008","journal-title":"Toxicol Sci"}],"container-title":["Environmental Health Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-pdf\/120\/5\/655\/66374259\/ehp.1104436.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-pdf\/120\/5\/655\/66374259\/ehp.1104436.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T13:43:41Z","timestamp":1786628621000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-lookup\/doi\/10.1289\/ehp.1104436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,30]]},"references-count":35,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2012,1,30]]},"published-print":{"date-parts":[[2012,5,1]]}},"URL":"https:\/\/doi.org\/10.1289\/ehp.1104436","relation":{},"ISSN":["0091-6765","1552-9924"],"issn-type":[{"value":"0091-6765","type":"print"},{"value":"1552-9924","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,30]]}}}