{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T10:46:24Z","timestamp":1782729984420,"version":"3.54.5"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":54,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R21ES035517"],"award-info":[{"award-number":["R21ES035517"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R01ES014032"],"award-info":[{"award-number":["R01ES014032"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["K99\/R00ES024808"],"award-info":[{"award-number":["K99\/R00ES024808"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Environmental Health Sciences,United States","award":["P42ES004705"],"award-info":[{"award-number":["P42ES004705"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Environ Health"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Over 100,000 people were exposed to arsenic-contaminated drinking water in Antofagasta, Chile from 1958\u20131970. Individuals born during this high exposure period have elevated rates of cancer, lung and cardiovascular disease, and hypertension. However, the mechanisms of long-term arsenic toxicity remain unclear. We investigated whether early-life arsenic exposure was associated with altered glucocorticoid levels in adulthood. This study included 114 individuals born in Antofagasta during the high exposure period and 118 individuals born in other Chilean cities with lower exposure. Arsenic exposure metrics were constructed based on residential histories and included: concentration at birth, peak and highest 5-year average between ages 0\u201310\u00a0years, and highest lifetime 5-year average, and lifetime cumulative exposure. Morning plasma cortisol concentrations were measured using a cell-based bioassay. Individuals in the highest quartile of highest lifetime 5-year average of arsenic exposure had approximately 11% lower mean log cortisol levels than those in the lowest quartile of exposure (\u03b2\u2009=\u2009-0.116; 95% CI: -0.229, -0.003). In sex-stratified analyses, associations were stronger among female participants. For example, female participants in the highest quartile of cumulative exposure had 22.0% lower cortisol levels compared to those in the lowest quartile (\u03b2\u2009=\u2009-0.248; 95% CI: -0.444, -0.053) and the test for interaction by sex was statistically significant (p\u2009=\u20090.036). This study is the first to show that early-life arsenic exposure may suppress HPA axis activity decades after exposure has ceased. These findings support endocrine disruption as a potential mechanism underlying long-term health effects of arsenic and highlight early development as a critical exposure window.<\/jats:p>","DOI":"10.1186\/s12940-026-01304-9","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T02:36:12Z","timestamp":1778034972000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-term effect of early-life arsenic exposure on morning plasma cortisol in adults from Antofagasta, Chile"],"prefix":"10.1186","volume":"25","author":[{"given":"Rosemarie","family":"de la Rosa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Steinmaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Nardone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Silveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Acevedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catterina","family":"Ferreccio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martyn T.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenna C. M.","family":"Sill\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"1304_CR1","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1016\/j.toxrep.2015.10.003","volume":"2","author":"AM Allan","year":"2015","unstructured":"Allan AM, Hafez AK, Labrecque MT, Solomon ER, Shaikh MN, Zheng X, et al. Sex-dependent effects of developmental arsenic exposure on methylation capacity and methylation regulation of the glucocorticoid receptor system in the embryonic mouse brain. Toxicol Rep. 2015;2:1376\u201390. https:\/\/doi.org\/10.1016\/j.toxrep.2015.10.003.","journal-title":"Toxicol Rep"},{"key":"1304_CR2","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1037\/a0017910","volume":"24","author":"DM Almeida","year":"2009","unstructured":"Almeida DM, Piazza JR, Stawski RS. Inter-individual differences and intra-individual variability in the cortisol awakening response: an examination of age and gender. Psychol Aging. 2009;24:819\u201327. https:\/\/doi.org\/10.1037\/a0017910.","journal-title":"Psychol Aging"},{"key":"1304_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15592294.2017.1320637","volume":"0","author":"AA Appleton","year":"2017","unstructured":"Appleton AA, Jackson BP, Karagas M, Marsit CJ. Prenatal exposure to neurotoxic metals is associated with increased placental glucocorticoid receptor DNA methylation. Epigenetics. 2017;0:1\u20139. https:\/\/doi.org\/10.1080\/15592294.2017.1320637.","journal-title":"Epigenetics"},{"key":"1304_CR4","doi-asserted-by":"publisher","DOI":"10.15620\/cdc:11481","volume-title":"Toxicological profile for arsenic","author":"ATSDR","year":"2007","unstructured":"ATSDR. Toxicological profile for arsenic. United States: Agency for Toxic Substances and Disease Registry; 2007. https:\/\/doi.org\/10.15620\/cdc:11481."},{"key":"1304_CR5","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1289\/ehp.1409360","volume":"124","author":"KA Bailey","year":"2016","unstructured":"Bailey KA, Smith AH, Tokar EJ, Graziano JH, Kim K-W, Navasumrit P, et al. Mechanisms underlying latent disease risk associated with early-life arsenic exposure: current research trends and scientific gaps. Environ Health Perspect. 2016;124:170\u20135. https:\/\/doi.org\/10.1289\/ehp.1409360.","journal-title":"Environ Health Perspect"},{"key":"1304_CR6","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1021\/tx060122q","volume":"19","author":"JE Bodwell","year":"2006","unstructured":"Bodwell JE, Gosse JA, Nomikos AP, Hamilton JW. Arsenic disruption of steroid receptor gene activation: complex dose-response effects are shared by several steroid receptors. Chem Res Toxicol. 2006;19:1619\u201329. https:\/\/doi.org\/10.1021\/tx060122q.","journal-title":"Chem Res Toxicol"},{"key":"1304_CR7","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1021\/tx0499113","volume":"17","author":"JE Bodwell","year":"2004","unstructured":"Bodwell JE, Kingsley LA, Hamilton JW. Arsenic at very low concentrations alters glucocorticoid receptor (GR)-mediated gene activation but not GR-mediated gene repression: complex dose-response effects are closely correlated with levels of activated GR and require a functional GR DNA binding domain. Chem Res Toxicol. 2004;17:1064\u201376. https:\/\/doi.org\/10.1021\/tx0499113.","journal-title":"Chem Res Toxicol"},{"key":"1304_CR8","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.ntt.2014.11.006","volume":"47","author":"KE Caldwell","year":"2015","unstructured":"Caldwell KE, Labrecque MT, Solomon BR, Ali A, Allan AM. Prenatal arsenic exposure alters the programming of the glucocorticoid signaling system during embryonic development. Neurotoxicol Teratol. 2015;47:66\u201379. https:\/\/doi.org\/10.1016\/j.ntt.2014.11.006.","journal-title":"Neurotoxicol Teratol"},{"key":"1304_CR9","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1080\/15592294.2015.1105424","volume":"10","author":"A Cardenas","year":"2015","unstructured":"Cardenas A, Houseman EA, Baccarelli AA, Quamruzzaman Q, Rahman M, Mostofa G, et al. In utero arsenic exposure and epigenome-wide associations in placenta, umbilical artery, and human umbilical vein endothelial cells. Epigenetics. 2015;10:1054\u201363. https:\/\/doi.org\/10.1080\/15592294.2015.1105424.","journal-title":"Epigenetics"},{"key":"1304_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2024.124721","volume":"360","author":"Y Chen","year":"2024","unstructured":"Chen Y, Pu Y, Liu H, Cao A, Du Y, He S, et al. A study on the mediating role of serum hormones in the effects of heavy metals on preeclampsia. Environ Pollut. 2024;360:124721. https:\/\/doi.org\/10.1016\/j.envpol.2024.124721.","journal-title":"Environ Pollut"},{"key":"1304_CR11","doi-asserted-by":"publisher","DOI":"10.3390\/toxics10040167","volume":"10","author":"S Choi","year":"2022","unstructured":"Choi S, Lee A, Choi G, Moon H-B, Kim S, Choi K, et al. Free cortisol mediates associations of maternal urinary heavy metals with neonatal anthropometric measures: a cross-sectional study. Toxics. 2022;10:167. https:\/\/doi.org\/10.3390\/toxics10040167.","journal-title":"Toxics"},{"key":"1304_CR12","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1007\/s00420-010-0591-6","volume":"84","author":"DC Dauphin\u00e9","year":"2011","unstructured":"Dauphin\u00e9 DC, Ferreccio C, Guntur S, Yuan Y, Hammond SK, Balmes J, et al. Lung function in adults following in utero and childhood exposure to arsenic in drinking water: preliminary findings. Int Arch Occup Environ Health. 2011;84:591\u2013600. https:\/\/doi.org\/10.1007\/s00420-010-0591-6.","journal-title":"Int Arch Occup Environ Health"},{"key":"1304_CR13","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1002\/etc.4903","volume":"40","author":"R de la Rosa","year":"2021","unstructured":"de la Rosa R, Vazquez S, Tachachartvanich P, Daniels SI, Sill\u00e9 F, Smith MT. Cell-based bioassay to screen environmental chemicals and human serum for total glucocorticogenic activity. Environ Toxicol Chem. 2021;40:177\u201386. https:\/\/doi.org\/10.1002\/etc.4903.","journal-title":"Environ Toxicol Chem"},{"key":"1304_CR14","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1210\/me.2013-1095","volume":"27","author":"AN Evans","year":"2013","unstructured":"Evans AN, Liu Y, MacGregor R, Huang V, Aguilera G. Regulation of hypothalamic corticotropin-releasing hormone transcription by elevated glucocorticoids. Mol Endocrinol. 2013;27:1796\u2013807. https:\/\/doi.org\/10.1210\/me.2013-1095.","journal-title":"Mol Endocrinol"},{"key":"1304_CR15","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1097\/00001648-200011000-00010","volume":"11","author":"C Ferreccio","year":"2000","unstructured":"Ferreccio C, Gonz\u00e1lez C, Milosavjlevic V, Marshall G, Sancha AM, Smith AH. Lung cancer and arsenic concentrations in drinking water in Chile. Epidemiology. 2000;11:673\u20139.","journal-title":"Epidemiology"},{"key":"1304_CR16","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1097\/EDE.0b013e31829e3e03","volume":"24","author":"C Ferreccio","year":"2013","unstructured":"Ferreccio C, Yuan Y, Calle J, Ben\u00edtez H, Parra RL, Acevedo J, et al. Arsenic, tobacco smoke, and occupation. Epidemiology. 2013;24:898\u2013905. https:\/\/doi.org\/10.1097\/EDE.0b013e31829e3e03.","journal-title":"Epidemiology"},{"key":"1304_CR17","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1016\/j.neuro.2012.08.010","volume":"33","author":"SL Goggin","year":"2012","unstructured":"Goggin SL, Labrecque MT, Allan AM. Perinatal exposure to 50 ppb sodium arsenate induces hypothalamic-pituitary-adrenal axis dysregulation in male C57BL\/6 mice. Neurotoxicology. 2012;33:1338\u201345. https:\/\/doi.org\/10.1016\/j.neuro.2012.08.010.","journal-title":"Neurotoxicology"},{"key":"1304_CR18","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1002\/jat.2898","volume":"34","author":"JA Gosse","year":"2014","unstructured":"Gosse JA, Taylor VF, Jackson BP, Hamilton JW, Bodwell JE. Monomethylated trivalent arsenic species disrupt steroid receptor interactions with their DNA response elements at non-cytotoxic cellular concentrations. J Appl Toxicol. 2014;34:498\u2013505. https:\/\/doi.org\/10.1002\/jat.2898.","journal-title":"J Appl Toxicol"},{"key":"1304_CR19","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1289\/ehp.10391","volume":"116","author":"BB Gump","year":"2008","unstructured":"Gump BB, Stewart P, Reihman J, Lonky E, Darvill T, Parsons PJ, et al. Low-level prenatal and postnatal blood lead exposure and adrenocortical responses to acute stress in children. Environ Health Perspect. 2008;116:249\u201355. https:\/\/doi.org\/10.1289\/ehp.10391.","journal-title":"Environ Health Perspect"},{"key":"1304_CR20","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.envres.2016.11.016","volume":"153","author":"EM Hall","year":"2017","unstructured":"Hall EM, Acevedo J, L\u00f3pez FG, Cort\u00e9s S, Ferreccio C, Smith AH, et al. Hypertension among adults exposed to drinking water arsenic in Northern Chile. Environ Res. 2017;153:99\u2013105. https:\/\/doi.org\/10.1016\/j.envres.2016.11.016.","journal-title":"Environ Res"},{"key":"1304_CR21","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1080\/17446651.2017.1356222","volume":"12","author":"MA Howland","year":"2017","unstructured":"Howland MA, Sandman CA, Glynn LM. Developmental origins of the human hypothalamic-pituitary-adrenal axis. Expert Rev Endocrinol Metab. 2017;12:321\u201339. https:\/\/doi.org\/10.1080\/17446651.2017.1356222.","journal-title":"Expert Rev Endocrinol Metab"},{"key":"1304_CR22","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1210\/jcem.83.1.4498","volume":"83","author":"NA Huizenga","year":"1998","unstructured":"Huizenga NA, Koper JW, de Lange P, Pols HA, Stolk RP, Grobbee DE, et al. Interperson variability but intraperson stability of baseline plasma Cortisol concentrations, and its relation to feedback sensitivity of the hypothalamo-pituitary-adrenal axis to a low dose of Dexamethasone in elderly individuals. J Clin Endocrinol Metab. 1998;83:47\u201354. https:\/\/doi.org\/10.1210\/jcem.83.1.4498.","journal-title":"J Clin Endocrinol Metab"},{"key":"1304_CR23","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1289\/ehp.01109245","volume":"109","author":"RC Kaltreider","year":"2001","unstructured":"Kaltreider RC, Davis AM, Lariviere JP, Hamilton JW. Arsenic alters the function of the Glucocorticoid Receptor as a transcription factor. Environ Health Perspect. 2001;109:245\u201351.","journal-title":"Environ Health Perspect"},{"key":"1304_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynstr.2021.100416","volume":"15","author":"J Klinger-K\u00f6nig","year":"2021","unstructured":"Klinger-K\u00f6nig J, Frenzel S, Hannemann A, Wittfeld K, B\u00fclow R, Friedrich N, et al. Sex differences in the association between basal serum Cortisol concentrations and cortical thickness. Neurobiol Stress. 2021;15:100416. https:\/\/doi.org\/10.1016\/j.ynstr.2021.100416.","journal-title":"Neurobiol Stress"},{"key":"1304_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2020.139964","volume":"739","author":"Z Li","year":"2020","unstructured":"Li Z, Li X, Qian Y, Guo C, Wang Z, Wei Y. The sustaining effects of e-waste-related metal exposure on hypothalamus-pituitary-adrenal axis reactivity and oxidative stress. Sci Total Environ. 2020;739:139964. https:\/\/doi.org\/10.1016\/j.scitotenv.2020.139964.","journal-title":"Sci Total Environ"},{"key":"1304_CR26","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.neuro.2008.05.004","volume":"29","author":"EJ Martinez","year":"2008","unstructured":"Martinez EJ, Kolb BL, Bell A, Savage DD, Allan AM. Moderate perinatal Arsenic exposure alters neuroendocrine markers associated with depression and increases depressive-like behaviors in adult mouse offspring. Neurotoxicology. 2008;29:647\u201355. https:\/\/doi.org\/10.1016\/j.neuro.2008.05.004.","journal-title":"Neurotoxicology"},{"key":"1304_CR27","unstructured":"Mayo Clinic Laboratories, 2025. CORT - Overview: Cortisol, Serum [WWW Document]. URL https:\/\/www.mayocliniclabs.com\/test-catalog\/overview\/8545#Clinical-and-Interpretive. Accessed 7 Sep 2025."},{"key":"1304_CR28","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1038\/nn.2270","volume":"12","author":"PO McGowan","year":"2009","unstructured":"McGowan PO, Sasaki A, D\u2019Alessio AC, Dymov S, Labont\u00e9 B, Szyf M, et al. Epigenetic regulation of the Glucocorticoid Receptor in human brain associates with childhood abuse. Nat Neurosci. 2009;12:342\u20138. https:\/\/doi.org\/10.1038\/nn.2270.","journal-title":"Nat Neurosci"},{"key":"1304_CR29","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1021\/acs.chemrestox.8b00352","volume":"32","author":"CJ Meakin","year":"2019","unstructured":"Meakin CJ, Martin EM, Szilagyi JT, Nylander-French LA, Fry RC. Inorganic Arsenic as an endocrine disruptor: modulation of the Glucocorticoid Receptor pathway in placental cells via CpG methylation. Chem Res Toxicol. 2019;32:493\u20139. https:\/\/doi.org\/10.1021\/acs.chemrestox.8b00352.","journal-title":"Chem Res Toxicol"},{"key":"1304_CR30","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.scitotenv.2016.12.112","volume":"581\u2013582","author":"KE Nachman","year":"2017","unstructured":"Nachman KE, Ginsberg GL, Miller MD, Murray CJ, Nigra AE, Pendergrast CB. Mitigating dietary Arsenic exposure: current status in the United States and recommendations for an improved path forward. Sci Total Environ. 2017;581\u2013582:221\u201336. https:\/\/doi.org\/10.1016\/j.scitotenv.2016.12.112.","journal-title":"Sci Total Environ"},{"key":"1304_CR31","doi-asserted-by":"publisher","DOI":"10.17226\/18594","volume-title":"Critical Aspects of EPA\u2019s IRIS Assessment of Inorganic Arsenic: Interim Report","author":"National Research Council","year":"2013","unstructured":"National Research Council. Critical Aspects of EPA\u2019s IRIS Assessment of Inorganic Arsenic: Interim Report. Washington, DC: The National Academies Press; 2013. https:\/\/doi.org\/10.17226\/18594."},{"key":"1304_CR32","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1289\/ehp.1205875","volume":"121","author":"MF Naujokas","year":"2013","unstructured":"Naujokas MF, Anderson B, Ahsan H, Aposhian HV, Graziano JH, Thompson C, et al. The broad scope of health effects from chronic Arsenic exposure: update on a worldwide public health problem. Environ Health Perspect. 2013;121:295\u2013302. https:\/\/doi.org\/10.1289\/ehp.1205875.","journal-title":"Environ Health Perspect"},{"key":"1304_CR33","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1210\/er.2015-1080","volume":"38","author":"H Oster","year":"2017","unstructured":"Oster H, Challet E, Ott V, Arvat E, de Kloet ER, Dijk D-J, et al. The functional and clinical significance of the 24-hour rhythm of circulating Glucocorticoids. Endocr Rev. 2017;38:3\u201345. https:\/\/doi.org\/10.1210\/er.2015-1080.","journal-title":"Endocr Rev"},{"key":"1304_CR34","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.chemosphere.2007.10.053","volume":"71","author":"B P\u00e9rez-Cadah\u00eda","year":"2008","unstructured":"P\u00e9rez-Cadah\u00eda B, Laffon B, Porta M, Lafuente A, Cabaleiro T, L\u00f3pez T, et al. Relationship between blood concentrations of heavy metals and cytogenetic and endocrine parameters among subjects involved in cleaning coastal areas affected by the \u201cPrestige\u201d tanker oil spill. Chemosphere. 2008;71:447\u201355. https:\/\/doi.org\/10.1016\/j.chemosphere.2007.10.053.","journal-title":"Chemosphere"},{"key":"1304_CR35","doi-asserted-by":"publisher","unstructured":"Podgorski J, Berg M. Global threat of arsenic in groundwater. Science. 2020;368:845\u201350 https:\/\/doi.org\/10.1126\/science.aba1510.","DOI":"10.1126\/science.aba1510"},{"key":"1304_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2011.21","volume":"1","author":"KM Radtke","year":"2011","unstructured":"Radtke KM, Ruf M, Gunter HM, Dohrmann K, Schauer M, Meyer A, et al. Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor. Transl Psychiatry. 2011;1:e21. https:\/\/doi.org\/10.1038\/tp.2011.21.","journal-title":"Transl Psychiatry"},{"key":"1304_CR37","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1001\/jama.2023.11305","volume":"330","author":"M Reincke","year":"2023","unstructured":"Reincke M, Fleseriu M. Cushing syndrome: a review. JAMA. 2023;330:170\u201381. https:\/\/doi.org\/10.1001\/jama.2023.11305.","journal-title":"JAMA"},{"key":"1304_CR38","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1016\/j.amjmed.2025.05.044","volume":"138","author":"M Ring","year":"2025","unstructured":"Ring M. An integrative approach to HPA Axis dysfunction: from recognition to recovery. Am J Med. 2025;138:1451\u201363. https:\/\/doi.org\/10.1016\/j.amjmed.2025.05.044.","journal-title":"Am J Med"},{"key":"1304_CR39","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.1093\/aje\/kwy159","volume":"187","author":"T Roh","year":"2018","unstructured":"Roh T, Steinmaus C, Marshall G, Ferreccio C, Liaw J, Smith AH. Age at exposure to arsenic in water and mortality 30\u201340 years after exposure cessation. Am J Epidemiol. 2018;187:2297\u2013305. https:\/\/doi.org\/10.1093\/aje\/kwy159.","journal-title":"Am J Epidemiol"},{"key":"1304_CR40","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph192114406","volume":"19","author":"B Ruffino","year":"2022","unstructured":"Ruffino B, Campo G, Crutchik D, Reyes A, Zanetti M. Drinking water supply in the region of Antofagasta (Chile): a challenge between past, present and future. Int J Environ Res Public Health. 2022;19:14406. https:\/\/doi.org\/10.3390\/ijerph192114406.","journal-title":"Int J Environ Res Public Health"},{"key":"1304_CR41","doi-asserted-by":"publisher","first-page":"266","DOI":"10.26444\/aaem\/104586","volume":"26","author":"MV Salgado","year":"2019","unstructured":"Salgado MV, Schisterman E, Pino P, Bangdiwala S, Mu\u00f1oz MP, Iglesias V. Is prenatal arsenic exposure associated with salivary cortisol in infants in Arica, Chile? An exploratory cohort study. Ann Agric Environ Med. 2019;26:266\u201372. https:\/\/doi.org\/10.26444\/aaem\/104586.","journal-title":"Ann Agric Environ Med"},{"key":"1304_CR42","doi-asserted-by":"publisher","DOI":"10.4172\/1948-5956.1000250","author":"D Sinha","year":"2014","unstructured":"Sinha D, Mukherjee B, Bindhani B, Dutta K, Saha H, Prasad P, et al. Chronic Low Level Arsenic Exposure Inflicts Pulmonary and Systemic Inflammation. J Cancer Sci Ther. 2014. https:\/\/doi.org\/10.4172\/1948-5956.1000250.","journal-title":"J Cancer Sci Ther"},{"key":"1304_CR43","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1007\/s40572-018-0184-1","volume":"5","author":"L Smeester","year":"2018","unstructured":"Smeester L, Fry RC. Long-term health effects and underlying biological mechanisms of developmental exposure to arsenic. Curr Environ Health Rep. 2018;5:134\u201344. https:\/\/doi.org\/10.1007\/s40572-018-0184-1.","journal-title":"Curr Environ Health Rep"},{"key":"1304_CR44","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1289\/ehp.1104867","volume":"120","author":"AH Smith","year":"2012","unstructured":"Smith AH, Marshall G, Liaw J, Yuan Y, Ferreccio C, Steinmaus C. Mortality in young adults following in utero and childhood exposure to arsenic in drinking water. Environ Health Perspect. 2012;120:1527\u201331. https:\/\/doi.org\/10.1289\/ehp.1104867.","journal-title":"Environ Health Perspect"},{"key":"1304_CR45","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1093\/jnci\/djx201","volume":"110","author":"AH Smith","year":"2018","unstructured":"Smith AH, Marshall G, Roh T, Ferreccio C, Liaw J, Steinmaus C. Lung, bladder, and kidney cancer mortality 40\u2009years after arsenic exposure reduction. J Natl Cancer Inst. 2018;110:241\u20139. https:\/\/doi.org\/10.1093\/jnci\/djx201.","journal-title":"J Natl Cancer Inst"},{"key":"1304_CR46","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1289\/ehp.8832","volume":"114","author":"AH Smith","year":"2006","unstructured":"Smith AH, Marshall G, Yuan Y, Ferreccio C, Liaw J, von Ehrenstein O, et al. Increased mortality from lung cancer and bronchiectasis in young adults after exposure to arsenic in utero and in early childhood. Environ Health Perspect. 2006;114:1293\u20136.","journal-title":"Environ Health Perspect"},{"key":"1304_CR47","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2020.114920","volume":"391","author":"ER Solomon","year":"2020","unstructured":"Solomon ER, Caldwell KK, Allan AM. Developmental arsenic exposure is associated with sex differences in the epigenetic regulation of stress genes in the adult mouse frontal cortex. Toxicol Appl Pharmacol. 2020;391:114920. https:\/\/doi.org\/10.1016\/j.taap.2020.114920.","journal-title":"Toxicol Appl Pharmacol"},{"key":"1304_CR48","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.envres.2017.01.012","volume":"154","author":"JN Souza-Talarico","year":"2017","unstructured":"Souza-Talarico JN, Suchecki D, Juster R-P, Plusquellec P, Barbosa F Jr, Bunscheit V, et al. Lead exposure is related to hypercortisolemic profiles and allostatic load in Brazilian older adults. Environ Res. 2017;154:261\u20138. https:\/\/doi.org\/10.1016\/j.envres.2017.01.012.","journal-title":"Environ Res"},{"key":"1304_CR49","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.psyneuen.2016.12.017","volume":"77","author":"T Stalder","year":"2017","unstructured":"Stalder T, Steudte-Schmiedgen S, Alexander N, Klucken T, Vater A, Wichmann S, et al. Stress-related and basic determinants of hair cortisol in humans: a meta-analysis. Psychoneuroendocrinology. 2017;77:261\u201374. https:\/\/doi.org\/10.1016\/j.psyneuen.2016.12.017.","journal-title":"Psychoneuroendocrinology"},{"key":"1304_CR50","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.taap.2016.10.006","volume":"313","author":"C Steinmaus","year":"2016","unstructured":"Steinmaus C, Ferreccio C, Acevedo J, Balmes JR, Liaw J, Troncoso P, et al. High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile. Toxicol Appl Pharmacol. 2016;313:10\u20135. https:\/\/doi.org\/10.1016\/j.taap.2016.10.006.","journal-title":"Toxicol Appl Pharmacol"},{"key":"1304_CR51","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1158\/1055-9965.EPI-14-0059","volume":"23","author":"C Steinmaus","year":"2014","unstructured":"Steinmaus C, Ferreccio C, Acevedo J, Yuan Y, Liaw J, Dur\u00e1n V, et al. Increased lung and bladder cancer incidence in adults after in utero and early-life arsenic exposure. Cancer Epidemiol Biomarkers Prev. 2014;23:1529\u201338. https:\/\/doi.org\/10.1158\/1055-9965.EPI-14-0059.","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"1304_CR52","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.envint.2016.07.020","volume":"95","author":"H-J Sun","year":"2016","unstructured":"Sun H-J, Xiang P, Luo J, Hong H, Lin H, Li H-B, et al. Mechanisms of arsenic disruption on gonadal, adrenal and thyroid endocrine systems in humans: a review. Environ Int. 2016;95:61\u20138. https:\/\/doi.org\/10.1016\/j.envint.2016.07.020.","journal-title":"Environ Int"},{"key":"1304_CR53","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1111\/j.1742-7843.2007.00168.x","volume":"102","author":"M Vahter","year":"2008","unstructured":"Vahter M. Health effects of early life exposure to arsenic. Basic Clin Pharmacol Toxicol. 2008;102:204\u201311. https:\/\/doi.org\/10.1111\/j.1742-7843.2007.00168.x.","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"1304_CR54","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2025.5485","author":"A Vaidya","year":"2025","unstructured":"Vaidya A, Findling J, Bancos I. Adrenal insufficiency in adults: a review. JAMA. 2025. https:\/\/doi.org\/10.1001\/jama.2025.5485.","journal-title":"JAMA"},{"key":"1304_CR55","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.neuroscience.2008.12.058","volume":"159","author":"MJ Weiser","year":"2009","unstructured":"Weiser MJ, Handa RJ. Estrogen impairs glucocorticoid dependent negative feedback on the hypothalamic-pituitary-adrenal axis via estrogen receptor alpha within the hypothalamus. Neuroscience. 2009;159:883\u201395. https:\/\/doi.org\/10.1016\/j.neuroscience.2008.12.058.","journal-title":"Neuroscience"},{"key":"1304_CR56","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1097\/EDE.0b013e3181c21e46","volume":"21","author":"Y Yuan","year":"2010","unstructured":"Yuan Y, Marshall G, Ferreccio C, Steinmaus C, Liaw J, Bates M, et al. Kidney cancer mortality: fifty-year latency patterns related to arsenic exposure. Epidemiology. 2010;21:103\u20138. https:\/\/doi.org\/10.1097\/EDE.0b013e3181c21e46.","journal-title":"Epidemiology"},{"key":"1304_CR57","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1093\/aje\/kwm238","volume":"166","author":"Y Yuan","year":"2007","unstructured":"Yuan Y, Marshall G, Ferreccio C, Steinmaus C, Selvin S, Liaw J, et al. Acute myocardial infarction mortality in comparison with lung and bladder cancer mortality in arsenic-exposed region II of Chile from 1950 to 2000. Am J Epidemiol. 2007;166:1381\u201391. https:\/\/doi.org\/10.1093\/aje\/kwm238.","journal-title":"Am J Epidemiol"}],"container-title":["Environmental Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12940-026-01304-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12940-026-01304-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12940-026-01304-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T10:03:10Z","timestamp":1782727390000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12940-026-01304-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,6]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1304"],"URL":"https:\/\/doi.org\/10.1186\/s12940-026-01304-9","relation":{},"ISSN":["1476-069X"],"issn-type":[{"value":"1476-069X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,6]]},"assertion":[{"value":"23 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Study participants provided informed consent, and protocols were approved by the Pontificia Universidad Cat\u00f3lica de Chile and the University of California, Berkeley Institutional Review Boards.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"56"}}