{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T06:54:44Z","timestamp":1782111284290,"version":"3.54.5"},"reference-count":97,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T00:00:00Z","timestamp":1720310400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007036","name":"Milj\u00f8styrelsen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007036","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014803","name":"EFSA","doi-asserted-by":"publisher","award":["GP\/EFSA\/PREV\/2022\/01"],"award-info":[{"award-number":["GP\/EFSA\/PREV\/2022\/01"]}],"id":[{"id":"10.13039\/100014803","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Reproductive Toxicology"],"published-print":{"date-parts":[[2024,9]]},"DOI":"10.1016\/j.reprotox.2024.108662","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T16:32:44Z","timestamp":1720456364000},"page":"108662","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["Methodology for developing data-rich Key Event Relationships for Adverse Outcome Pathways exemplified by linking decreased androgen receptor activity with decreased anogenital distance"],"prefix":"10.1016","volume":"128","author":[{"given":"Marie L.","family":"Holmer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Zilliacus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica K.","family":"Draskau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrieta","family":"Hlisn\u00edkov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Beronius","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.reprotox.2024.108662_bib1","unstructured":"Daniel Villeneuve, Bette Meek, Barbara Viviani, Tanja Burgdorf, Carlie La.Lone, Jason O.\u2019Brien, Dries Knapen, Michelle Angrish, Rex FitzGerald, Shihori Tanabe. AOP WIKI Handbook. Developers\u2019 Handbook 2.6, 2023. \u3008https:\/\/aopwiki.org\/handbooks\/4\u3009."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib2","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1093\/toxsci\/kfab113","article-title":"A pragmatic approach to adverse outcome pathway development and evaluation","volume":"184","author":"Svingen","year":"2021","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.reprotox.2024.108662_bib3","article-title":"AOP key event relationship report: linking decreased retinoic acid levels with disrupted meiosis in developing oocytes","volume":"3","author":"Draskau","year":"2022","journal-title":"Curr. Res. Toxicol."},{"key":"10.1016\/j.reprotox.2024.108662_bib4","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.reprotox.2022.07.004","article-title":"AOP key event relationship report: linking decreased androgen receptor activation with decreased granulosa cell proliferation of gonadotropin-independent follicles","volume":"112","author":"Panagiotou","year":"2022","journal-title":"Reprod. Toxicol."},{"key":"10.1016\/j.reprotox.2024.108662_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/j.crtox.2022.100085","article-title":"AOP key event relationship report: linking androgen receptor antagonism with nipple retention","volume":"3","author":"Pedersen","year":"2022","journal-title":"Curr. Res. Toxicol."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib6","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s00204-018-2350-5","article-title":"Anogenital distance as a toxicological or clinical marker for fetal androgen action and risk for reproductive disorders","volume":"93","author":"Schwartz","year":"2019","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.reprotox.2024.108662_bib7","doi-asserted-by":"crossref","unstructured":"OECD, Test No. 421: Reproduction\/Developmental Toxicity Screening Test, OECD Guidelines for the Testing of Chemicals, Section 4. OECD, 2016. \u3008https:\/\/doi.org\/10.1787\/9789264264380-en\u3009.","DOI":"10.1787\/9789264264380-en"},{"key":"10.1016\/j.reprotox.2024.108662_bib8","doi-asserted-by":"crossref","unstructured":"OECD, Test No. 422: Combined Repeated Dose Toxicity Study with the Reproduction\/Developmental Toxicity Screening Test, OECD Guidelines for the Testing of Chemicals, Section 4. OECD, 2016. \u3008https:\/\/doi.org\/10.1787\/9789264264403-en\u3009.","DOI":"10.1787\/9789264264403-en"},{"key":"10.1016\/j.reprotox.2024.108662_bib9","doi-asserted-by":"crossref","unstructured":"OECD, Test No. 443: Extended One-Generation Reproductive Toxicity Study, OECD Guidelines for the Testing of Chemicals, Section 4. OECD, 2018. \u3008https:\/\/doi.org\/10.1787\/9789264185371-en\u3009.","DOI":"10.1787\/9789264185371-en"},{"key":"10.1016\/j.reprotox.2024.108662_bib10","doi-asserted-by":"crossref","unstructured":"OECD, Test No. 414: Prenatal Developmental Toxicity Study, OECD Guidelines for the Testing of Chemicals, Section 4. OECD, 2018. \u3008https:\/\/doi.org\/10.1787\/9789264070820-en\u3009.","DOI":"10.1787\/9789264070820-en"},{"key":"10.1016\/j.reprotox.2024.108662_bib11","unstructured":"OECD, Guidance Document on Mammalian Reproductive Toxicity Testing and Assessment, OECD Environment, Health and Safety Publications, 2008. \u3008https:\/\/one.oecd.org\/document\/env\/jm\/mono(2008)16\/en\/pdf\u3009."},{"key":"10.1016\/j.reprotox.2024.108662_bib12","unstructured":"OECD, Guidance Document Supporting Oecd Test Guideline 443 on the Extended Onegeneration Reproductive Toxicity Test, OECD Environment, Health and Safety Publications, 2013. \u3008https:\/\/one.oecd.org\/document\/ENV\/JM\/MONO(2013)10\/en\/pdf\u3009."},{"issue":"6","key":"10.1016\/j.reprotox.2024.108662_bib13","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1210\/jc.2012-4057","article-title":"Anogenital distance or digit length ratio as measures of fetal androgen exposure: relationship to male reproductive development and its disorders","volume":"98","author":"Dean","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"4","key":"10.1016\/j.reprotox.2024.108662_bib14","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1111\/andr.12156","article-title":"Anogenital distance as a marker of androgen exposure in humans","volume":"4","author":"Thankamony","year":"2016","journal-title":"Andrology"},{"issue":"In Press","key":"10.1016\/j.reprotox.2024.108662_bib15","article-title":"Aop report: an upstream network for reduced androgen signalling leading to altered gene expression of ar responsive genes in target tissues","author":"Draskau","year":"2024","journal-title":"Environ. Toxicol. Chem."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108662_bib16","first-page":"3","article-title":"Androgen receptor structure, function and biology: from bench to bedside","volume":"37","author":"Davey","year":"2016","journal-title":"Clin. Biochem. Rev."},{"key":"10.1016\/j.reprotox.2024.108662_bib17","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1210\/edrv.23.2.0460","article-title":"Androgen Receptor (AR) Coregulators: An Overview","volume":"23","author":"Heinlein","year":"2002","journal-title":"Endocr Rev"},{"issue":"1","key":"10.1016\/j.reprotox.2024.108662_bib18","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1476-069X-3-8","article-title":"Anogenital distance in human male and female newborns: a descriptive, cross-sectional study","volume":"3","author":"Salazar-Martinez","year":"2004","journal-title":"Environ. Health"},{"issue":"4","key":"10.1016\/j.reprotox.2024.108662_bib19","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1172\/JCI34241","article-title":"Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism","volume":"118","author":"Welsh","year":"2008","journal-title":"J. Clin. Investig."},{"issue":"5","key":"10.1016\/j.reprotox.2024.108662_bib20","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1159\/000357932","article-title":"Development of the external genitalia and their sexual dimorphic regulation in mice","volume":"8","author":"Ipulan","year":"2014","journal-title":"Sex. Dev."},{"issue":"6","key":"10.1016\/j.reprotox.2024.108662_bib21","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1177\/106002809002400612","article-title":"Flutamide: an antiandrogen for advanced prostate cancer","volume":"24","author":"Goldspiel","year":"1990","journal-title":"DICP"},{"key":"10.1016\/j.reprotox.2024.108662_bib22","doi-asserted-by":"crossref","unstructured":"OECD, Test No. 458: Stably Transfected Human Androgen Receptor Transcriptional Activation Assay for Detection of Androgenic Agonist and Antagonist Activity of Chemicals, OECD Guidelines for the Testing of Chemicals, Section 4, OECD, 2023. \u3008https:\/\/doi.org\/10.1787\/9789264264366-en\u3009.","DOI":"10.1787\/9789264264366-en"},{"issue":"3","key":"10.1016\/j.reprotox.2024.108662_bib23","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/0303-7207(86)90132-2","article-title":"Characteristics of interaction of the antiandrogen flutamide with the androgen receptor in various target tissues","volume":"44","author":"Simard","year":"1986","journal-title":"Mol. Cell. Endocrinol."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib24","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2131\/jts.18.83","article-title":"The Affinity of Procymidone to Androgen Receptor in Rats and Mice","volume":"18","author":"Hosokawa","year":"1993","journal-title":"J. Toxicol. Sci."},{"issue":"1\u20132","key":"10.1016\/j.reprotox.2024.108662_bib25","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1177\/074823379901500108","article-title":"The Fungicide Procymidone Alters Sexual Differentiation in the Male Rat by Acting as an Androgen-Receptor Antagonist in Vivo and in Vitro","volume":"15","author":"Ostby","year":"1999","journal-title":"Toxicol. Ind. Health"},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib26","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.reprotox.2012.05.090","article-title":"Adverse effects on sexual development in rat offspring after low dose exposure to a mixture of endocrine disrupting pesticides","volume":"34","author":"Hass","year":"2012","journal-title":"Reprod. Toxicol."},{"issue":"5","key":"10.1016\/j.reprotox.2024.108662_bib27","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1289\/ehp.6649","article-title":"Screening for Estrogen and Androgen Receptor Activities in 200 Pesticides by in Vitro Reporter Gene Assays Using Chinese Hamster Ovary Cells","volume":"112","author":"Kojima","year":"2004","journal-title":"Environ. Health Perspect."},{"issue":"6","key":"10.1016\/j.reprotox.2024.108662_bib28","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1289\/ehp.1002895","article-title":"Widely Used Pesticides with Previously Unknown Endocrine Activity Revealed as\u00a0in Vitro\u00a0Antiandrogens","volume":"119","author":"Orton","year":"2011","journal-title":"Environ. Health Perspect."},{"issue":"11","key":"10.1016\/j.reprotox.2024.108662_bib29","doi-asserted-by":"crossref","DOI":"10.1289\/EHP6774","article-title":"Quantitative\u00a0in Vitro\u00a0to\u00a0in Vivo\u00a0Extrapolation (QIVIVE) for Predicting Reduced Anogenital Distance Produced by Anti-Androgenic Pesticides in a Rodent Model for Male Reproductive Disorders","volume":"128","author":"Scholze","year":"2020","journal-title":"Environ. Health Perspect."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108662_bib30","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1006\/taap.1996.7966","article-title":"Vinclozolin Andp,P\u2032-DDE Alter Androgen-Dependent Gene Expression:In VivoConfirmation of an Androgen Receptor-Mediated Mechanism","volume":"142","author":"Kelce","year":"1997","journal-title":"Toxicol. Appl. Pharmacol."},{"issue":"34","key":"10.1016\/j.reprotox.2024.108662_bib31","doi-asserted-by":"crossref","DOI":"10.1074\/jbc.270.34.19998","article-title":"Androgen receptor antagonist versus agonist activities of the fungicide vinclozolin relative to hydroxyflutamide","volume":"270","author":"Wong","year":"1995","journal-title":"J. Biol. Chem."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib32","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1093\/toxsci\/69.2.332","article-title":"Response-Surface Modeling of the Effect of 5alpha-Dihydrotestosterone and Androgen Receptor Levels on the Response to the Androgen Antagonist Vinclozolin","volume":"69","author":"Euling","year":"2002","journal-title":"Toxicol. Sci."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108662_bib33","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.taap.2006.04.005","article-title":"Steroid Receptor Profiling of Vinclozolin and Its Primary Metabolites","volume":"216","author":"Molina-Molina","year":"2006","journal-title":"Toxicol. Appl. Pharmacol."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib34","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0300-483X(02)00044-6","article-title":"Comparison of antiandrogenic activities of vinclozolin and d,l-camphorquinone in androgen receptor gene transcription assay in vitro and mouse in utero exposure assay in vivo","volume":"174","author":"Shimamura","year":"2002","journal-title":"Toxicology"},{"issue":"10","key":"10.1016\/j.reprotox.2024.108662_bib35","doi-asserted-by":"crossref","first-page":"3640","DOI":"10.1073\/pnas.87.10.3640","article-title":"Structural and Biochemical Properties of Cloned and Expressed Human and Rat Steroid 5 Alpha-Reductases","volume":"87","author":"Andersson","year":"1990","journal-title":"Proc. Natl. Acad. Sci."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib36","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1056\/NEJM199401133300208","article-title":"Finasteride","volume":"330","author":"Rittmaster","year":"1994","journal-title":"N. Engl. J. Med."},{"issue":"3","key":"10.1016\/j.reprotox.2024.108662_bib37","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/0960-0760(90)90487-6","article-title":"The Clinical Development of a 5\u03b1-Reductase Inhibitor, Finasteride","volume":"37","author":"Stoner","year":"1990","journal-title":"J. Steroid Biochem. Mol. Biol."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108662_bib38","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.reprotox.2003.10.011","article-title":"Steroidogenesis in Fetal Male Rats Is Reduced by DEHP and DINP, but Endocrine Effects of DEHP Are Not Modulated by DEHA in Fetal, Prepubertal and Adult Male Rats","volume":"18","author":"Borch","year":"2004","journal-title":"Reprod. Toxicol."},{"issue":"1\u20132","key":"10.1016\/j.reprotox.2024.108662_bib39","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.tox.2006.03.015","article-title":"Mechanisms underlying the anti-androgenic effects of diethylhexyl phthalate in fetal rat testis","volume":"223","author":"Borch","year":"2006","journal-title":"Toxicology"},{"issue":"6","key":"10.1016\/j.reprotox.2024.108662_bib40","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1095\/biolreprod.107.065649","article-title":"In utero exposure to di-(2-ethylhexyl) phthalate exerts both short-term and long-lasting suppressive effects on testosterone production in the rat1","volume":"78","author":"Culty","year":"2008","journal-title":"Biol. Reprod."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108662_bib41","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1093\/toxsci\/kfr146","article-title":"Dose-response assessment of fetal testosterone production and gene expression levels in rat testes following inutero exposure to diethylhexyl phthalate, diisobutyl phthalate, diisoheptyl phthalate, and diisononyl phthalate","volume":"123","author":"Hannas","year":"2011","journal-title":"Toxicol. Sci."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib42","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1093\/toxsci\/kfr315","article-title":"Genomic biomarkers of phthalate-induced male reproductive developmental toxicity: a targeted RT-PCR array approach for defining relative potency","volume":"125","author":"Hannas","year":"2012","journal-title":"Toxicol. Sci."},{"issue":"6","key":"10.1016\/j.reprotox.2024.108662_bib43","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1530\/REP-12-0266","article-title":"Novel molecular targets associated with testicular dysgenesis induced by gestational exposure to diethylhexyl phthalate in the rat: a role for estradiol","volume":"144","author":"Klinefelter","year":"2012","journal-title":"Reproduction"},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib44","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1093\/toxsci\/58.2.339","article-title":"The Plasticizer Diethylhexyl Phthalate Induces Malformations by Decreasing Fetal Testosterone Synthesis during Sexual Differentiation in the Male Rat","volume":"58","author":"Parks","year":"2000","journal-title":"Toxicol. Sci."},{"issue":"3","key":"10.1016\/j.reprotox.2024.108662_bib45","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.toxlet.2003.09.012","article-title":"Phthalate Ester-Induced Gubernacular Lesions Are Associated with Reduced Insl3 Gene Expression in the Fetal Rat Testis","volume":"146","author":"Wilson","year":"2004","journal-title":"Toxicol. Lett."},{"issue":"3","key":"10.1016\/j.reprotox.2024.108662_bib46","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.toxlet.2007.03.004","article-title":"Differential expression of the phthalate syndrome in male Sprague\u2013Dawley and wistar rats after in utero DEHP exposure","volume":"170","author":"Wilson","year":"2007","journal-title":"Toxicol. Lett."},{"issue":"4","key":"10.1016\/j.reprotox.2024.108662_bib47","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1262\/jrd.20220","article-title":"Differential effects of flutamide and di-(2-ethylhexyl) phthalate on male reproductive organs in a rat model","volume":"55","author":"Vo","year":"2009","journal-title":"J. Reprod. Dev."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib48","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1093\/toxsci\/62.2.236","article-title":"Androgen-mediated development in male rat offspring exposed to flutamide in utero: permanence and correlation of early postnatal changes in anogenital distance and nipple retention with malformations in androgen-dependent tissues","volume":"62","author":"McIntyre","year":"2001","journal-title":"Toxicol. Sci."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib49","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1093\/toxsci\/kfi159","article-title":"Changes in androgen-mediated reproductive development in male rat offspring following exposure to a single oral dose of flutamide at different gestational ages","volume":"85","author":"Foster","year":"2005","journal-title":"Toxicol. Sci."},{"issue":"Suppl. 1","key":"10.1016\/j.reprotox.2024.108662_bib50","doi-asserted-by":"crossref","first-page":"S122","DOI":"10.1289\/ehp.9360","article-title":"Combined exposure to anti-androgens exacerbates disruption of sexual differentiation in the rat","volume":"115","author":"Hass","year":"2007","journal-title":"Environ. Health Perspect."},{"issue":"5","key":"10.1016\/j.reprotox.2024.108662_bib51","doi-asserted-by":"crossref","first-page":"517","DOI":"10.2131\/jts.29.517","article-title":"Effects of flutamide on sex maturation and behavior of offspring born to female rats treated during late pregnancy","volume":"29","author":"Goto","year":"2004","journal-title":"J. Toxicol. Sci."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108662_bib52","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.tox.2004.12.004","article-title":"Effects of in utero and lactational exposure to flutamide in SD rats: comparison of the effects of administration periods","volume":"209","author":"Kanji","year":"2005","journal-title":"Toxicology"},{"issue":"12","key":"10.1016\/j.reprotox.2024.108662_bib53","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1007\/s00204-015-1622-6","article-title":"Investigations of putative reproductive toxicity of low-dose exposures to flutamide in wistar rats","volume":"89","author":"Fussell","year":"2015","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.reprotox.2024.108662_bib54","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.tox.2016.08.021","article-title":"Manipulation of pre and postnatal androgen environments and anogenital distance in rats","volume":"368\u2013369","author":"Kita","year":"2016","journal-title":"Toxicology"},{"issue":"4-5","key":"10.1016\/j.reprotox.2024.108662_bib55","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/S0031-9384(03)00120-3","article-title":"Play, Copulation, Anatomy, and Testosterone in Gonadally Intact Male Rats Prenatally Exposed to Flutamide","volume":"79","author":"Casto","year":"2003","journal-title":"Physiol. Behav."},{"issue":"3","key":"10.1016\/j.reprotox.2024.108662_bib56","doi-asserted-by":"crossref","first-page":"299","DOI":"10.2131\/jts.35.299","article-title":"Maternal exposure to procymidone has no effects on fetal external genitalia development in male rabbit fetuses in a modified developmental toxicity study","volume":"35","author":"Inawaka","year":"2010","journal-title":"J. Toxicol. Sci."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108662_bib57","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1093\/toxsci\/55.1.152","article-title":"Characterization of the period of sensitivity of fetal male sexual development to vinclozolin","volume":"55","author":"Wolf","year":"2000","journal-title":"Toxicol. Sci."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108662_bib58","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1006\/taap.1994.1227","article-title":"Developmental effects of an environmental antiandrogen: the fungicide vinclozolin alters sex differentiation of the male rat","volume":"129","author":"Gray","year":"1994","journal-title":"Toxicol. Appl. Pharm."},{"issue":"Special","key":"10.1016\/j.reprotox.2024.108662_bib59","doi-asserted-by":"crossref","first-page":"S163","DOI":"10.2131\/jts.30.S163","article-title":"Evaluation of a two-generation reproduction toxicity study adding endopoints to detect endocrine disrupting activity using vinclozolin","volume":"30","author":"Matsuura","year":"2005","journal-title":"J. Toxicol. Sci."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108662_bib60","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1093\/toxsci\/kfh018","article-title":"Interactive effects of vinclozolin and testosterone propionate on pregnancy and sexual differentiation of the male and female SD rat","volume":"78","author":"Wolf","year":"2004","journal-title":"Toxicol. Sci."},{"issue":"6","key":"10.1016\/j.reprotox.2024.108662_bib61","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1289\/ehp.7509","article-title":"Perinatal Exposure to Low Levels of the Environmental Antiandrogen Vinclozolin Alters Sex-Differentiated Social Play and Sexual Behaviors in the Rat","volume":"113","author":"Colbert","year":"2005","journal-title":"Environ. Health Perspect."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108662_bib62","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1006\/rtph.2000.1400","article-title":"Pre- and Postnatal Oral Toxicity of Vinclozolin in Wistar and Long\u2013Evans Rats","volume":"32","author":"Hellwig","year":"2000","journal-title":"Regul. Toxicol. Pharmacol."},{"issue":"12","key":"10.1016\/j.reprotox.2024.108662_bib63","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1289\/ehp.0900689","article-title":"Synergistic Disruption of External Male Sex Organ Development by a Mixture of Four Antiandrogens","volume":"117","author":"Christiansen","year":"2009","journal-title":"Environ. Health Perspect."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108662_bib64","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.yrtph.2010.09.010","article-title":"Vinclozolin: A Feasibility and Sensitivity Study of the ILSI-HESI F1-Extended One-Generation Rat Reproduction Protocol","volume":"59","author":"Schneider","year":"2011","journal-title":"Regul. Toxicol. Pharmacol."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib65","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1093\/toxsci\/kfg128","article-title":"Effects of in utero exposure to finasteride on androgen-dependent reproductive development in the male rat","volume":"74","author":"Bowman","year":"2003","journal-title":"Toxicol. Sci."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108662_bib66","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1006\/taap.1993.1041","article-title":"Critical developmental periods for effects on male rat genitalia induced by finasteride, a 5\u03b1-reductase inhibitor","volume":"119","author":"Clark","year":"1993","journal-title":"Toxicol. Appl. Pharm."},{"issue":"12","key":"10.1016\/j.reprotox.2024.108662_bib67","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1089\/jmf.2010.0279","article-title":"Effects of in utero exposure to D-004, a lipid extract from Roystonea regia fruits, in the male rat: a comparison with finasteride","volume":"14","author":"Mart\u00ednez","year":"2011","journal-title":"J. Med. Food"},{"issue":"1\u20132","key":"10.1016\/j.reprotox.2024.108662_bib68","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1177\/074823379901500109","volume":"15","author":"Wolf","year":"1999","journal-title":"Toxicol. Ind. Health"},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib69","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1093\/toxsci\/58.2.350","article-title":"Perinatal Exposure to the Phthalates DEHP, BBP, and DINP, but Not DEP, DMP, or DOTP, Alters Sexual Differentiation of the Male Rat","volume":"58","author":"Gray","year":"2000","journal-title":"Toxicol. Sci."},{"issue":"3","key":"10.1016\/j.reprotox.2024.108662_bib70","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1289\/ehp.01109229","article-title":"Abnormalities of sexual development in male rats with in utero and lactational exposure to the antiandrogenic plasticizer di(2-ethylhexyl) phthalate","volume":"109","author":"Moore","year":"2001","journal-title":"Environ. Health Perspect."},{"issue":"4","key":"10.1016\/j.reprotox.2024.108662_bib71","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.reprotox.2004.11.005","article-title":"Antiandrogenic effects in male rats perinatally exposed to a mixture of di(2-ethylhexyl) phthalate and di(2-ethylhexyl) adipate","volume":"19","author":"Jarfelt","year":"2005","journal-title":"Reprod. Toxicol."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108662_bib72","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.tox.2006.05.007","article-title":"A dose\u2013response study following in utero and lactational exposure to di-(2-Ethylhexyl) phthalate (DEHP): effects on androgenic status, developmental landmarks and testicular histology in male offspring rats","volume":"225","author":"Andrade","year":"2006","journal-title":"Toxicology"},{"issue":"4","key":"10.1016\/j.reprotox.2024.108662_bib73","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1007\/s00244-009-9385-9","article-title":"Vitamin C and Resveratrol Supplementation to Rat Dams Treated with Di(2-Ethylhexyl)Phthalate: Impact on Reproductive and Oxidative Stress End Points in Male Offspring","volume":"57","author":"Botelho","year":"2009","journal-title":"Arch. Environ. Contam. Toxicol."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib74","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/toxsci\/kfp109","article-title":"Transgenerational Effects of Di (2-Ethylhexyl) Phthalate in the Male CRL:CD(SD) Rat: Added Value of Assessing Multiple Offspring per Litter","volume":"110","author":"Gray","year":"2009","journal-title":"Toxicol. Sci."},{"issue":"5","key":"10.1016\/j.reprotox.2024.108662_bib75","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1095\/biolreprod.108.072975","article-title":"In utero and lactational exposures to diethylhexyl-phthalate affect two populations of leydig cells in male long-evans rats1","volume":"80","author":"Lin","year":"2009","journal-title":"Biol. Reprod."},{"key":"10.1016\/j.reprotox.2024.108662_bib76","doi-asserted-by":"crossref","unstructured":"Anderson J.\u00a0Martino-Andrade, Rosana N. Morais, Giuliana G. K. Botelho, Graziela Muller, Simone W. Grande, Giovanna B. Carpentieri, Gabriel M. C. Le\u00e3o, Paulo R. Dalsenter, coadministration of active phthalates results in disruption of foetal testicular function in rats, Int. J. Androl., vol. 32(no. 6), 2009, pp. 704\u201312. \u3008https:\/\/doi.org\/10.1111\/j.1365-2605.2008.00939.x\u3009.","DOI":"10.1111\/j.1365-2605.2008.00939.x"},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib77","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.reprotox.2008.07.006","article-title":"Diisobutyl phthalate impairs the androgen-dependent reproductive development of the male rat","volume":"26","author":"Saillenfait","year":"2008","journal-title":"Reprod. Toxicol."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib78","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.reprotox.2010.04.005","article-title":"Low-dose perinatal exposure to di(2-ethylhexyl) phthalate induces anti-androgenic effects in male rats","volume":"30","author":"Christiansen","year":"2010","journal-title":"Reprod. Toxicol."},{"issue":"4","key":"10.1016\/j.reprotox.2024.108662_bib79","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.reprotox.2012.09.006","article-title":"Non-monotonic dose effects of in utero exposure to di(2-ethylhexyl) phthalate (DEHP) on testicular and serum testosterone and anogenital distance in male mouse fetuses","volume":"34","author":"Do","year":"2012","journal-title":"Reprod. Toxicol."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib80","doi-asserted-by":"crossref","first-page":"139","DOI":"10.4067\/S0716-97602013000200004","article-title":"Disruption of reproductive development in male rat offspring following gestational and lactational exposure to di-(2-ethylhexyl) phthalate and genistein","volume":"46","author":"Zhang","year":"2013","journal-title":"Biol. Res."},{"key":"10.1016\/j.reprotox.2024.108662_bib81","doi-asserted-by":"crossref","DOI":"10.1093\/toxsci\/kfx019","article-title":"Teratogenic Effects of\u00a0in Utero\u00a0Exposure to Di-(2-Ethylhexyl)-Phthalate (DEHP) in B6:129S4 Mice","author":"Ungewitter","year":"2017","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.reprotox.2024.108662_bib82","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.tox.2019.03.008","article-title":"Effects of in utero and lactational exposure to phthalates on reproductive development and glycemic homeostasis in rats","volume":"421","author":"Venturelli","year":"2019","journal-title":"Toxicology"},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib83","doi-asserted-by":"crossref","DOI":"10.1016\/j.yexcr.2020.112151","article-title":"Maternal exposure to di-(2-ethylhexyl) phthalate (DEHP) activates the PI3K\/Akt\/MTOR signaling pathway in F1 and F2 generation adult mouse testis","volume":"394","author":"Zhang","year":"2020","journal-title":"Exp. Cell Res."},{"issue":"4","key":"10.1016\/j.reprotox.2024.108662_bib84","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1111\/andr.12180","article-title":"Timing of Prenatal Phthalate Exposure in Relation to Genital Endpoints in Male Newborns","volume":"4","author":"Martino\u2010Andrade","year":"2016","journal-title":"Andrology"},{"issue":"8","key":"10.1016\/j.reprotox.2024.108662_bib85","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1289\/ehp.8100","article-title":"Decrease in anogenital distance among male infants with prenatal phthalate exposure","volume":"113","author":"Swan","year":"2005","journal-title":"Environ. Health Perspect."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib86","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.envres.2008.08.007","article-title":"Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans","volume":"108","author":"Swan","year":"2008","journal-title":"Environ. Res."},{"key":"10.1016\/j.reprotox.2024.108662_bib87","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.envint.2017.10.007","article-title":"Influence of race on prenatal phthalate exposure and anogenital measurements among boys and girls","volume":"110","author":"Wenzel","year":"2018","journal-title":"Environ. Int."},{"key":"10.1016\/j.reprotox.2024.108662_bib88","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.envint.2018.08.034","article-title":"Prenatal Exposure to Phthalates and Phenols and Infant Endocrine-Sensitive Outcomes: The MIREC Study","volume":"120","author":"Arbuckle","year":"2018","journal-title":"Environ. Int."},{"key":"10.1016\/j.reprotox.2024.108662_bib89","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2023.161914","article-title":"Maternal phthalate exposure during pregnancy and testis function of young adult sons","volume":"871","author":"Henriksen","year":"2023","journal-title":"Sci. Total Environ."},{"issue":"7","key":"10.1016\/j.reprotox.2024.108662_bib90","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1289\/ehp.1509870","article-title":"Prenatal Exposure to Phthalates and Anogenital Distance in Male Infants from a Low-Exposed Danish Cohort (2010\u20132012)","volume":"124","author":"Jensen","year":"2016","journal-title":"Environ. Health Perspect."},{"key":"10.1016\/j.reprotox.2024.108662_bib91","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.reprotox.2019.05.065","article-title":"Prenatal Bisphenol a and Phthalate Exposure Are Risk Factors for Male Reproductive System Development and Cord Blood Sex Hormone Levels","author":"Sunman","year":"2019","journal-title":"Reprod. Toxicol."},{"key":"10.1016\/j.reprotox.2024.108662_bib92","doi-asserted-by":"crossref","unstructured":"Anna Lanzoni, Anna F. Castoldi, George E.N. Kass, Andrea Terron, Guilhem De Seze, Anna Bal-Price, Fr\u00e9d\u00e9ric Y. Bois, et al., Advancing human health risk assessment. EFSA Journal 17, no. Proceedings of the Third EFSA Scientific Conference: Science, Food and Society Guest Editors: Y. Devos, K.C. Elliott, A. Hardy, 2019. https:\/\/doi.org\/10.2903\/j.efsa.2019.e170712.","DOI":"10.2903\/j.efsa.2019.e170712"},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib93","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.bbagrm.2014.05.020","article-title":"Androgens and mammalian male reproductive tract development","volume":"1849","author":"Murashima","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA) - Gene Regul. Mech."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108662_bib94","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1210\/en.2014-1534","article-title":"Anogenital distance plasticity in adulthood: implications for its use as a biomarker of fetal androgen action","volume":"156","author":"Mitchell","year":"2015","journal-title":"Endocrinology"},{"issue":"2","key":"10.1016\/j.reprotox.2024.108662_bib95","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.diabres.2014.04.006","article-title":"Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes","volume":"105","author":"Esser","year":"2014","journal-title":"Diabetes Res. Clin. Pract."},{"key":"10.1016\/j.reprotox.2024.108662_bib96","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ejogrb.2016.08.026","article-title":"Obesity, type 2 diabetes mellitus and cardiovascular disease risk: an uptodate in the management of polycystic ovary syndrome","volume":"207","author":"Orio","year":"2016","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"issue":"S12","key":"10.1016\/j.reprotox.2024.108662_bib97","doi-asserted-by":"crossref","first-page":"3816","DOI":"10.1002\/1097-0142(19931215)72:12+<3816::AID-CNCR2820721711>3.0.CO;2-3","article-title":"Mechanism of action and pure antiandrogenic properties of flutamide","volume":"72","author":"Labrie","year":"1993","journal-title":"Cancer"}],"container-title":["Reproductive Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0890623824001291?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0890623824001291?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T01:18:23Z","timestamp":1728436703000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0890623824001291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9]]},"references-count":97,"alternative-id":["S0890623824001291"],"URL":"https:\/\/doi.org\/10.1016\/j.reprotox.2024.108662","relation":{},"ISSN":["0890-6238"],"issn-type":[{"value":"0890-6238","type":"print"}],"subject":[],"published":{"date-parts":[[2024,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Methodology for developing data-rich Key Event Relationships for Adverse Outcome Pathways exemplified by linking decreased androgen receptor activity with decreased anogenital distance","name":"articletitle","label":"Article Title"},{"value":"Reproductive Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.reprotox.2024.108662","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"108662"}}