{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:09:40Z","timestamp":1790762980747,"version":"4.1.0"},"reference-count":51,"publisher":"American Chemical Society (ACS)","issue":"12","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":2333,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: Bisphenol A (BPA) is a synthetic estrogen commonly used in polycarbonate plastic and resin-lined food and beverage containers. Exposure of animal and cell models to doses of BPA below the recommended tolerable daily intake (TDI) of 50 \u03bcg\/kg\/day have been shown to alter specific estrogen-responsive gene expression, but this has not previously been shown in humans.<\/jats:p>\n                  <jats:p>Objective: We investigated associations between BPA exposure and in vivo estrogenic gene expression in humans.<\/jats:p>\n                  <jats:p>Methods: We studied 96 adult men from the InCHIANTI population study and examined in vivo expression of six estrogen receptor, estrogen-related receptor, and androgen receptor genes in peripheral blood leukocytes.<\/jats:p>\n                  <jats:p>Results: The geometric mean urinary BPA concentration was 3.65 ng\/mL [95% confidence interval (CI): 3.13, 4.28], giving an estimated mean excretion of 5.84 \u03bcg\/day (95% CI: 5.00, 6.85), significantly below the current TDI. In age-adjusted models, there were positive associations between higher BPA concentrations and higher ESR2 [estrogen receptor 2 (ER beta)] expression (unstandardized linear regression coefficient = 0.1804; 95% CI: 0.0388, 0.3221; p = 0.013) and ESRRA (estrogen related receptor alpha) expression (coefficient = 0.1718; 95% CI: 0.0213, 0.3223; p = 0.026): These associations were little changed after adjusting for potential confounders, including obesity, serum lipid concentrations, and white cell subtype percentages. Upper-tertile BPA excretors (urinary BPA &amp;gt; 4.6 ng\/mL) had 65% higher mean ESR2 expression than did lower-tertile BPA excretors (0\u20132.4 ng\/mL).<\/jats:p>\n                  <jats:p>Conclusions: Because activation of nuclear-receptor\u2013mediated pathways by BPA is consistently found in laboratory studies, such activation in humans provides evidence that BPA is likely to function as a xenoestrogen in this sample of adults.<\/jats:p>","DOI":"10.1289\/ehp.1103809","type":"journal-article","created":{"date-parts":[[2011,8,10]],"date-time":"2011-08-10T14:57:36Z","timestamp":1312988256000},"page":"1788-1793","source":"Crossref","is-referenced-by-count":62,"title":["Bisphenol A Exposure Is Associated with\n                    <i>in Vivo<\/i>\n                    Estrogenic Gene Expression in Adults"],"prefix":"10.1021","volume":"119","author":[{"given":"David","family":"Melzer","sequence":"first","affiliation":[{"name":"Epidemiology and Public Health, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorna","family":"Harries","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Cipelli","sequence":"additional","affiliation":[{"name":"Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Henley","sequence":"additional","affiliation":[{"name":"Epidemiology and Public Health, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathryn","family":"Money","sequence":"additional","affiliation":[{"name":"Brixham Environmental Laboratory, AstraZeneca UK Ltd., Brixham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"McCormack","sequence":"additional","affiliation":[{"name":"Brixham Environmental Laboratory, AstraZeneca UK Ltd., Brixham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Young","sequence":"additional","affiliation":[{"name":"Brixham Environmental Laboratory, AstraZeneca UK Ltd., Brixham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Guralnik","sequence":"additional","affiliation":[{"name":"Laboratory of Epidemiology, Demography, and Biometry, an"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Ferrucci","sequence":"additional","affiliation":[{"name":"Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Bandinelli","sequence":"additional","affiliation":[{"name":"InCHIANTI Group, Piero Palagi Hospital, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Corsi","sequence":"additional","affiliation":[{"name":"InCHIANTI Group, Piero Palagi Hospital, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Galloway","sequence":"additional","affiliation":[{"name":"Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2011,8,10]]},"reference":[{"issue":"suppl 1","key":"2026080608043020100_micit1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1289\/ehp.9368","article-title":"Endocrine-disrupting potential of bisphenol A, bisphenol A dimethacrylate, 4-n-nonylphenol, and 4-n-octylphenol in vitro: new data and a brief review.","volume":"115","author":"Bonefeld-J\u00f8rgensen","year":"2007","journal-title":"Environ Health Perspect"},{"key":"2026080608043020100_micit2","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1289\/ehp.0900979","article-title":"Prenatal bisphenol A exposure and early childhood behavior.","volume":"117","author":"Braun","year":"2009","journal-title":"Environ Health Perspect"},{"key":"2026080608043020100_micit3","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1289\/ehp.7534","article-title":"Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population.","volume":"113","author":"Calafat","year":"2005","journal-title":"Environ Health Perspect"},{"key":"2026080608043020100_micit4","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1289\/ehp.10753","article-title":"Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003\u20132004.","volume":"116","author":"Calafat","year":"2008","journal-title":"Environ Health Perspect"},{"key":"2026080608043020100_micit5","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/978-1-59745-553-4_13","article-title":"RNA stabilization of peripheral blood and profiling by bead chip analysis.","volume":"496","author":"Debey-Pascher","year":"2009","journal-title":"Methods Mol Biol"},{"key":"2026080608043020100_micit6","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/137996a0","article-title":"Synthetic estrogenic agents without the phenanthrene nucleus","volume":"137","author":"Dodds","year":"1936","journal-title":"Nature"},{"key":"2026080608043020100_micit7","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.cmet.2007.03.007","article-title":"Genome-wide orchestration of cardiac functions by the orphan nuclear receptors ERR\u03b1 and \u03b3.","volume":"5","author":"Dufour","year":"2007","journal-title":"Cell Metab"},{"issue":"7186","key":"2026080608043020100_micit8","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/nature06758","article-title":"Genetics of gene expression and its effect on disease.","volume":"452","author":"Emilsson","year":"2008","journal-title":"Nature"},{"key":"2026080608043020100_micit9","author":"European Food Safety Authority","year":"2010"},{"key":"2026080608043020100_micit10","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1111\/j.1532-5415.2000.tb03873.x","article-title":"Subsystems contributing to the decline in ability to walk: bridging the gap between epidemiology and geriatric practice in the InCHIANTI study.","volume":"48","author":"Ferrucci","year":"2000","journal-title":"J Am Geriatr Soc"},{"key":"2026080608043020100_micit11","doi-asserted-by":"publisher","first-page":"e1000108","DOI":"10.1371\/journal.pgen.1000108","article-title":"Metabolic actions of estrogen receptor beta (ER\u03b2) are mediated by a negative cross-talk with PPAR\u03b3.","volume":"4","author":"Foryst-Ludwig","year":"2008","journal-title":"PLoS Genet"},{"key":"2026080608043020100_micit12","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1289\/ehp.1002367","article-title":"Daily bisphenol A excretion and associations with sex hormone concentrations: results from the InCHIANTI adult population study.","volume":"118","author":"Galloway","year":"2010","journal-title":"Environ Health Perspect"},{"key":"2026080608043020100_micit13","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/S1043-2760(02)00592-1","article-title":"To ERR in the estrogen pathway.","volume":"13","author":"Gigu\u00e8re","year":"2002","journal-title":"Trends Endocrinol Metab"},{"key":"2026080608043020100_micit14","first-page":"1","article-title":"Weight-of-evidence evaluation of reproductive and developmental effects of low doses of bisphenol A.","volume":"20","author":"Goodman","year":"2008","journal-title":"Crit Rev 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The Study Design.Available: http:\/\/www.inchiantistudy.net\/study.html [accessed 2 August 2011]."},{"key":"2026080608043020100_micit20","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1001\/jama.300.11.1303","article-title":"Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults.","volume":"300","author":"Lang","year":"2008","journal-title":"JAMA"},{"key":"2026080608043020100_micit21","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1093\/toxsci\/kfg150","article-title":"Antiandrogenic effects of bisphenol A and nonylphenol on the function of androgen receptor.","volume":"75","author":"Lee","year":"2003","journal-title":"Toxicol Sci"},{"key":"2026080608043020100_micit22","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method.","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"2026080608043020100_micit23","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1289\/ehp.10605","article-title":"Temporal variability and predictors of urinary bisphenol A concentrations in men and women.","volume":"116","author":"Mahalingaiah","year":"2008","journal-title":"Environ Health Perspect"},{"key":"2026080608043020100_micit24","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1021\/tx0001833","article-title":"In vitro and in vivo interactions of bisphenol A and its metabolite, bisphenol A glucuronide, with estrogen receptors \u03b1 and \u03b2.","volume":"14","author":"Matthews","year":"2001","journal-title":"Chem Res Toxicol"},{"key":"2026080608043020100_micit25","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1021\/es9028292","article-title":"Urinary bisphenol A concentration in relation to serum thyroid and reproductive hormones in men from an infertility clinic.","volume":"44","author":"Meeker","year":"2010","journal-title":"Environ Sci Technol"},{"issue":"1","key":"2026080608043020100_micit26","doi-asserted-by":"publisher","first-page":"e8673","DOI":"10.1371\/journal.pone.0008673","article-title":"Association of urinary bisphenol A concentration with heart disease: evidence from NHANES 2003\/06.","volume":"5","author":"Melzer","year":"2010","journal-title":"PLoS One"},{"key":"2026080608043020100_micit27","doi-asserted-by":"crossref","first-page":"5185","DOI":"10.1210\/jc.2002-020209","article-title":"Thyroid hormone action is disrupted by bisphenol A as an antagonist.","volume":"87","author":"Moriyama","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2026080608043020100_micit28","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1080\/00498250110040501","article-title":"Metabolism and cytotoxicity of bisphenol A and other bisphenols in isolated rat hepatocytes.","volume":"31","author":"Nakagawa","year":"2001","journal-title":"Xenobiotica"},{"key":"2026080608043020100_micit29","unstructured":"National Center for Biotechnology Information\n          . 2011. PubMed Nucleotide.Available: http:\/\/www.ncbi.nlm.nih.gov\/nuccore [accessed 26 October 2011]."},{"issue":"6","key":"2026080608043020100_micit30","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/j.envres.2009.04.004","article-title":"Within-person variability in urinary bisphenol A concentrations: measurements from specimens after long term storage.","volume":"109","author":"Nepomnaschy","year":"2009","journal-title":"Environ Res"},{"key":"2026080608043020100_micit31","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/j.1365-2605.2007.00858.x","article-title":"Effects of endocrine disruptors on obesity.","volume":"31","author":"Newbold","year":"2008","journal-title":"Int J Androl"},{"key":"2026080608043020100_micit32","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1289\/ehp.10587","article-title":"Direct evidence revealing structural elements essential for the high binding ability of bisphenol A to human estrogen-related receptor.","volume":"116","author":"Okada","year":"2008","journal-title":"Environ Health Perspect"},{"key":"2026080608043020100_micit33","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.toxlet.2010.04.017","article-title":"In vivo estrogenic potential of 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene, an active metabolite of bisphenol A, in uterus of ovariectomized rat.","volume":"197","author":"Okuda","year":"2010","journal-title":"Toxicol Lett"},{"key":"2026080608043020100_micit34","first-page":"1","article-title":"The estrogen-related receptor alpha: the oldest, yet an energetic orphan with robust biological functions.","volume":"2010","author":"Ranhotra","year":"2010","journal-title":"J Recept Signal Transduct"},{"key":"2026080608043020100_micit35","unstructured":"R Development Core Team\n          . 2010. R Project for Statistical Computing.Available: http:\/\/www.r-project.org\/ [acceessed 20 January 2011]."},{"key":"2026080608043020100_micit36","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1289\/ehp.9804","article-title":"Estradiol and bisphenol a stimulate androgen receptor and estrogen receptor gene expression in fetal mouse prostate mesenchyme cells.","volume":"115","author":"Richter","year":"2007","journal-title":"Environ Health Perspect"},{"key":"2026080608043020100_micit37","first-page":"14","article-title":"Debating BPA\u2019s toxicity.","volume":"89","author":"Ritter","year":"2011","journal-title":"Chem Eng News"},{"key":"2026080608043020100_micit38","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/j.1365-2605.2007.00832.x","article-title":"Bisphenol A disruption of the endocrine pancreas and blood glucose homeostasis.","volume":"31","author":"Ropero","year":"2008","journal-title":"Int J Androl"},{"issue":"2","key":"2026080608043020100_micit39","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1093\/humrep\/dep385","article-title":"Bisphenol A and sexual dysfunction in men.","volume":"25","author":"Sharpe","year":"2010","journal-title":"Hum Reprod"},{"key":"2026080608043020100_micit40","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1677\/jme.0.0190299","article-title":"The mouse estrogen receptor-related orphan receptor alpha 1: molecular cloning and estrogen responsiveness.","volume":"19","author":"Shigeta","year":"1997","journal-title":"J Mol Endocrinol"},{"key":"2026080608043020100_micit41","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1289\/ehp.0800376","article-title":"Bisphenol A data in NHANES suggest longer than expected half life, substantial nonfood exposure, or both.","volume":"117","author":"Stahlhut","year":"2009","journal-title":"Environ Health 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human health at current levels of exposure.","volume":"24","author":"vom Saal","year":"2007","journal-title":"Reprod Toxicol"},{"key":"2026080608043020100_micit49","author":"Wood SN","year":"2006"},{"key":"2026080608043020100_micit50","first-page":"5695","article-title":"Modulation of aromatase expression in the breast tissue by ERR-1 orphan receptor.","volume":"58","author":"Yang","year":"1998","journal-title":"Cancer Res"},{"key":"2026080608043020100_micit51","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1007\/s00216-010-4344-x","article-title":"In-vitro oxidation of bisohenol A: is bisphenol A catechol a suitable biomarker for human exposure to bisphenol A?","volume":"399","author":"Ye","year":"2011","journal-title":"Anal Bioanal Chem"}],"container-title":["Environmental Health 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