{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T20:09:13Z","timestamp":1785442153193,"version":"3.56.0"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007036","name":"Danish Environmental Protection Agency","doi-asserted-by":"publisher","award":["2020-68044"],"award-info":[{"award-number":["2020-68044"]}],"id":[{"id":"10.13039\/501100007036","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology and Applied Pharmacology"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.taap.2025.117577","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T06:16:25Z","timestamp":1758521785000},"page":"117577","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["In vitro disruption of the retinoic acid signaling pathway by industrial chemicals and pharmaceuticals"],"prefix":"10.1016","volume":"505","author":[{"given":"Anna Kjerstine","family":"Rosenmai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisun","family":"Paik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Bay","family":"Wedebye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nichlas","family":"Davidsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecillie","family":"Henriksen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikala","family":"Melchiors","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terje","family":"Svingen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.taap.2025.117577_bb0005","doi-asserted-by":"crossref","first-page":"5213","DOI":"10.1111\/jcmm.17546","article-title":"Effect of isotretinoin (Netlook) on the testis of adult male albino rats and the role of omega 3 supplementation: a histological and biochemical study","volume":"26","author":"Al-Shahed","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"10.1016\/j.taap.2025.117577_bb0010","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1590\/S1516-89132008000600010","article-title":"Ketoconazole- and fluconazole-induced embryotoxicity and skeletal anomalies in Wistar rats: a comparative study","volume":"51","author":"Amaral","year":"2008","journal-title":"Braz. Arch. Biol. Technol."},{"key":"10.1016\/j.taap.2025.117577_bb0015","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2164\/jandrol.110.010751","article-title":"Suppression of spermatogenesis by bisdichloroacetyldiamines is mediated by inhibition of testicular retinoic acid biosynthesis","volume":"32","author":"Amory","year":"2011","journal-title":"J. Androl."},{"key":"10.1016\/j.taap.2025.117577_bb0020","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1194\/jlr.M054718","article-title":"Importance of ALDH1A enzymes in determining human testicular retinoic acid concentrations","volume":"56","author":"Arnold","year":"2015","journal-title":"J. Lipid Res."},{"key":"10.1016\/j.taap.2025.117577_bb0025","series-title":"Toxicological Profile for Endrin","author":"ATSDR","year":"2021"},{"key":"10.1016\/j.taap.2025.117577_bb0030","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/0041-008X(77)90140-5","article-title":"Enhancement of aspirin-induced teratogenicity by food restriction in rats","volume":"39","author":"Beall","year":"1977","journal-title":"Toxicol. Appl. Pharmacol."},{"issue":"3","key":"10.1016\/j.taap.2025.117577_bb0035","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1126\/science.1125691","article-title":"Retinoid Signaling determines germ cell fate in mice","volume":"1979","author":"Bowles","year":"2006","journal-title":"Science"},{"key":"10.1016\/j.taap.2025.117577_bb0040","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1042\/bj2720391","article-title":"Ligand specificities of recombinant retinoic acid receptors RARa and RAR","volume":"272","author":"Crettaz","year":"1990","journal-title":"Biochem. J."},{"key":"10.1016\/j.taap.2025.117577_bb0045","doi-asserted-by":"crossref","DOI":"10.1038\/nrm3932","article-title":"Mechanisms of retinoic acid signalling and its roles in organ and limb development","author":"Cunningham","year":"2015","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.taap.2025.117577_bb0050","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.taap.2017.03.001","article-title":"Embryotoxic and pharmacologic potency ranking of six azoles in the rat whole embryo culture by morphological and transcriptomic analysis","volume":"322","author":"Dimopoulou","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.taap.2025.117577_bb0055","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2008.09.002","article-title":"Retinoic acid synthesis and signaling during early organogenesis","author":"Duester","year":"2008","journal-title":"Cell"},{"key":"10.1016\/j.taap.2025.117577_bb0060","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/bdrb.20098","article-title":"Developmental toxic effects of antifungal flusilazole administered by gavage to mice","volume":"80","author":"Farag","year":"2007","journal-title":"Birth Defects Res. B Dev. Reprod. Toxicol."},{"key":"10.1016\/j.taap.2025.117577_bb0065","article-title":"Retinoic acid signaling pathways","volume":"146","author":"Ghyselinck","year":"2019","journal-title":"Development (Cambridge)"},{"key":"10.1016\/j.taap.2025.117577_bb0070","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.reprotox.2020.03.002","article-title":"Regulatory needs and activities to address the retinoid system in the context of endocrine disruption: the European viewpoint","volume":"93","author":"Grignard","year":"2020","journal-title":"Reprod. Toxicol."},{"key":"10.1016\/j.taap.2025.117577_bb0075","article-title":"Pharmacological inhibition of ALDH1A enzymes suppresses weight gain in a mouse model of diet-induced obesity","volume":"93\u2013101","author":"Haenisch","year":"2018","journal-title":"Obes. Res. Clin. Pract."},{"key":"10.1016\/j.taap.2025.117577_bb0080","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0006-2952(94)00491-9","article-title":"Inhibition of rat liver low Km aldehyde dehydrogenase by thiocarbamate herbicides occupational implications","volume":"49","author":"Hart","year":"1995","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.taap.2025.117577_bb0085","series-title":"List of Endocrine Disrupting Chemicals","author":"Hass","year":"2017"},{"key":"10.1016\/j.taap.2025.117577_bb0090","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.taap.2014.06.023","article-title":"Fenitrothion action at the endocannabinoid system leading to spermatotoxicity in Wistar rats","volume":"279","author":"Ito","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.taap.2025.117577_bb0095","article-title":"Retinoic acid synthesis and functions in early embryonic development","author":"Kam","year":"2025","journal-title":"Cell Biosci."},{"key":"10.1016\/j.taap.2025.117577_bb0100","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1289\/ehp.1510385","article-title":"Systems toxicology of male reproductive development: profiling 774 chemicals for molecular targets and adverse outcomes","volume":"4","author":"Leung","year":"2016","journal-title":"Environ. Health Perspect."},{"key":"10.1016\/j.taap.2025.117577_bb0105","doi-asserted-by":"crossref","DOI":"10.1016\/j.taap.2024.116843","article-title":"In vitro assessment of potential endocrine disrupting activities of chlorinated paraffins of various chain lengths","volume":"484","author":"Melchiors","year":"2024","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.taap.2025.117577_bb0110","doi-asserted-by":"crossref","DOI":"10.1016\/j.etap.2023.104069","article-title":"A method for in vitro data and structure curation to optimize for QSAR modelling of minimum absolute potency levels and a comparative use case","volume":"98","author":"Nikolov","year":"2023","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"10.1016\/j.taap.2025.117577_bb0115","series-title":"Guidance Document on the Validation of (Quantitative) Structure-Activity Relationship [(Q)SAR] Models","volume":"20","author":"OECD","year":"2014"},{"key":"10.1016\/j.taap.2025.117577_bb0120","doi-asserted-by":"crossref","first-page":"32160","DOI":"10.1074\/jbc.M010086200","article-title":"Expression and characterization of a murine enzyme able to cleave \u03b2-carotene. The formation of retinoids","volume":"276","author":"Paik","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.taap.2025.117577_bb0125","doi-asserted-by":"crossref","first-page":"15104","DOI":"10.1074\/jbc.M113.540211","article-title":"Inhibition of retinoic acid biosynthesis by the bisdichloroacetyldiamine WIN 18,446 markedly suppresses spermatogenesis and alters retinoid metabolism in mice","volume":"289","author":"Paik","year":"2014","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.taap.2025.117577_bb0130","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.contraception.2018.03.035","article-title":"Can inhibition of retinoic acid biosynthesis function as a non-hormonal female contraceptive?","volume":"98","author":"Paik","year":"2018","journal-title":"Contraception"},{"key":"10.1016\/j.taap.2025.117577_bb0135","article-title":"Return to fertility, toxicology, and transgenerational impact of treatment with WIN 18,446, a potential male contraceptive, in mice","volume":"9","author":"Paik","year":"2024","journal-title":"Contraception"},{"key":"10.1016\/j.taap.2025.117577_bb0140","article-title":"Kinetics of the inhibition and recovery of spermatogenesis induced by treatment with WIN 18,446, a male contraceptive, in mice","author":"Paik","year":"2024","journal-title":"Andrology"},{"key":"10.1016\/j.taap.2025.117577_bb0145","doi-asserted-by":"crossref","DOI":"10.1016\/j.reprotox.2017.05.014","article-title":"Retinoic acid in developmental toxicology: teratogen, morphogen and biomarker","author":"Piersma","year":"2017","journal-title":"Reprod. Toxicol."},{"key":"10.1016\/j.taap.2025.117577_bb0150","author":"Research Group for Chemical Risk Assessment and GMO, N.F.I.T.U. of D"},{"key":"10.1016\/j.taap.2025.117577_bb0155","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1111\/and.12467","article-title":"Quercetin mitigates fenitrothion-induced testicular toxicity in rats","volume":"48","author":"Saber","year":"2016","journal-title":"Andrologia"},{"key":"10.1016\/j.taap.2025.117577_bb0160","doi-asserted-by":"crossref","DOI":"10.1002\/biot.202300659","article-title":"Development and validation of CYP26A1 inhibition assay for high-throughput screening","volume":"19","author":"Sakamuru","year":"2024","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.taap.2025.117577_bb0165","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s11745-001-0755-z","article-title":"Inhibition of purified pig and human liver retinyl ester hydrolase by pharmacologic agents","volume":"36","author":"Schindler","year":"2001","journal-title":"Lipids"},{"key":"10.1016\/j.taap.2025.117577_bb0170","doi-asserted-by":"crossref","DOI":"10.1002\/wdev.264","article-title":"New insights and changing paradigms in the regulation of vitamin a metabolism in development","author":"Shannon","year":"2017","journal-title":"Wiley Interdiscip. Rev. Dev. Biol."},{"key":"10.1016\/j.taap.2025.117577_bb0175","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.vascn.2014.01.007","article-title":"Development of yeast reporter assay for screening specific ligands of retinoic acid and retinoid X receptor subtypes","volume":"69","author":"Shiizaki","year":"2014","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"10.1016\/j.taap.2025.117577_bb0180","article-title":"Predictive models of prenatal developmental toxicity from toxcast high-throughput screening data","volume":"4","author":"Sipes","year":"2011","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.taap.2025.117577_bb0185","doi-asserted-by":"crossref","DOI":"10.1016\/S0022-3565(24)39233-X","article-title":"R115866 inhibits all-trans-retinoic acid metabolism and exerts retinoidal effects in rodents","volume":"293","author":"Stoppie","year":"2000","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.taap.2025.117577_bb0190","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2024.174717","article-title":"Screening (ant)agonistic activities of xenobiotics on the retinoic acid receptor alpha (RAR\u03b1) using in vitro and in silico analysis","volume":"947","author":"Su","year":"2024","journal-title":"Sci. Total Environ."},{"key":"10.1016\/j.taap.2025.117577_bb0195","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2023.115876","article-title":"Impaired spermatogenesis and associated endocrine effects of azole fungicides in peripubertal Xenopus tropicalis","volume":"270","author":"Svanholm","year":"2024","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"10.1016\/j.taap.2025.117577_bb0200","doi-asserted-by":"crossref","first-page":"3204","DOI":"10.1016\/j.bmc.2014.03.047","article-title":"Retinoic acid receptor agonist activity of naturally occurring diterpenes","volume":"22","author":"Tanabe","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.taap.2025.117577_bb0205","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1046\/j.1523-1747.2000.00066.x","article-title":"3-cis retinoic acid exerts its specific activity on human sebocytes through selective intracellular isomerization to all-trans retinoic acid and binding to retinoid acid receptors","volume":"115","author":"Tsukada","year":"2000","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.taap.2025.117577_bb0210","author":"US EPA"},{"key":"10.1016\/j.taap.2025.117577_bb0215","series-title":"Development and application of QSAR models of retinoic acid receptor antagonism","author":"Wedebye","year":"2025"}],"container-title":["Toxicology and Applied Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X25003539?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X25003539?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T05:08:58Z","timestamp":1780722538000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0041008X25003539"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":43,"alternative-id":["S0041008X25003539"],"URL":"https:\/\/doi.org\/10.1016\/j.taap.2025.117577","relation":{},"ISSN":["0041-008X"],"issn-type":[{"value":"0041-008X","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"In vitro disruption of the retinoic acid signaling pathway by industrial chemicals and pharmaceuticals","name":"articletitle","label":"Article Title"},{"value":"Toxicology and Applied Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.taap.2025.117577","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"117577"}}