{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:59:18Z","timestamp":1790290758228,"version":"4.1.0"},"reference-count":31,"publisher":"American Chemical Society (ACS)","issue":"8","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":4323,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The Organisation for Economic Cooperation and Development (OECD) has completed phase 1 of the Hershberger validation intended to identify in vivo activity of suspected androgens and anti-androgens. Seventeen laboratories from 7 countries participated in phase 1, and results were collated and evaluated by the OECD with the support of an international committee of experts. Five androgen-responsive tissues (ventral prostate, paired seminal vesicles and coagulating glands, levator ani and bulbocavernosus muscles, glans penis, and paired Cowper\u2019s or bulbourethral glands) were evaluated. The standardized protocols used selected doses of a reference androgen, testosterone propionate (TP), and an antiandrogen, flutamide (FLU). All laboratories successfully detected TP-stimulated increases in androgen-responsive tissue weight and decreases in TP-stimulated tissue weights when FLU was co-administered. The standardized protocols performed well under a variety of conditions (e.g., strain, diet, housing protocol, bedding). There was good agreement among laboratories with regard to the TP doses inducing significant increases in tissue weights and the FLU doses decreasing TP-stimulated tissue weights. Several additional procedures (e.g., weighing of the dorsolateral prostate and fixation of tissues before weighing) and serum component measurements (e.g., luteinizing hormone) were also included by some laboratories to assess their potential utility. The results indicated that the OECD Hershberger protocol was robust, reproducible, and transferable across laboratories. Based on this phase 1 validation study, the protocols have been refined, and the next phase of the OECD validation program will test the protocol with selected doses of weak androgen agonists, androgen antagonists, a 5\u03b1-reductase inhibitor, and chemicals having no androgenic activity.<\/jats:p>","DOI":"10.1289\/ehp.8751","type":"journal-article","created":{"date-parts":[[2006,2,27]],"date-time":"2006-02-27T14:16:12Z","timestamp":1141049772000},"page":"1259-1265","source":"Crossref","is-referenced-by-count":38,"title":["The OECD Program to Validate the Rat Hershberger Bioassay to Screen Compounds\nfor\n                    <i>in Vivo<\/i>\n                    Androgen and Antiandrogen Responses. Phase 1: Use of a Potent Agonist\nand a Potent Antagonist to Test the Standardized Protocol"],"prefix":"10.1021","volume":"114","author":[{"given":"William","family":"Owens","sequence":"first","affiliation":[{"name":"Procter & Gamble, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Errol","family":"Zeiger","sequence":"additional","affiliation":[{"name":"Errol Zeiger Consulting, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Walker","sequence":"additional","affiliation":[{"name":"Health Canada, Ottawa, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Ashby","sequence":"additional","affiliation":[{"name":"Syngenta Central Toxicology Laboratory, Macclesfield, Cheshire, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley","family":"Onyon","sequence":"additional","affiliation":[{"name":"World Health Organization, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"L. Earl","family":"Gray","sequence":"additional","affiliation":[{"name":"U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2006,2,27]]},"reference":[{"key":"2026081311020517900_micit1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1006\/rtph.1999.1372","article-title":"Preliminary evaluation of the major protocol variables for the Hershberger\ncastrated male rat assay for the detection of androgens, antiandrogens, and\nmetabolic modulators","volume":"31","author":"Ashby","year":"2000","journal-title":"Regul Toxicol Pharmacol"},{"key":"2026081311020517900_micit2","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1210\/endo-89-1-16","article-title":"Studies on the inhibition of fetal androgen formation: inhibition of testosterone\nsynthesis in rat and rabbit fetal testes with observations\non reproductive tract development","volume":"89","author":"Bloch","year":"1971","journal-title":"Endocrinology"},{"key":"2026081311020517900_micit3","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1042\/bj0281360","article-title":"Conditions of hypertrophy of seminal vesicles in rats. II. The effect of\nderivatives of oestrone (memformon)","volume":"28","author":"David","year":"1934","journal-title":"Biochem J"},{"key":"2026081311020517900_micit4","author":"Dorfman"},{"key":"2026081311020517900_micit5","author":"Dorfman"},{"key":"2026081311020517900_micit6","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1080\/01621459.1955.10501294","article-title":"A multiple comparisons procedure for comparing several treatments with\na control","volume":"50","author":"Dunnett","year":"1955","journal-title":"J Am Stat Assoc"},{"key":"2026081311020517900_micit7","doi-asserted-by":"crossref","first-page":"482","DOI":"10.2307\/2528490","article-title":"New tables for multiple comparisons with a control","volume":"20","author":"Dunnett","year":"1964","journal-title":"Biometrics"},{"key":"2026081311020517900_micit8","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S0022-3565(25)04222-3","article-title":"The levator ani muscle of the rat as an index of myotrophic activity of\nsteroidal hormones","volume":"99","author":"Eisenberg","year":"1950","journal-title":"J Pharmacol Exp Ther"},{"key":"2026081311020517900_micit9","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1210\/endo-45-2-113","article-title":"Testosterone and tissue respiration of the castrate male rat with a possible\ntest for mytrophic activity","volume":"45","author":"Eisenberg","year":"1949","journal-title":"Endocrinology"},{"key":"2026081311020517900_micit10","author":"European Commission\/OECD"},{"key":"2026081311020517900_micit11","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1210\/endo-88-2-527","article-title":"Production of hypospadias in the rat by selective inhibition of fetal testicular 17\u03b1-hydroxylase and C17\u201326-lyase","volume":"88","author":"Goldman","year":"1971","journal-title":"Endocrinology"},{"key":"2026081311020517900_micit12","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S0890-6238(97)00025-7","article-title":"Endocrine screening methods workshop report: detection of estrogenic and\nandrogenic hormonal and antihormonal activity for chemicals that act\nvia receptor or steroidogenic enzyme mechanisms","volume":"11","author":"Gray","year":"1997","journal-title":"Reprod Toxicol"},{"key":"2026081311020517900_micit13","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3181\/00379727-83-20301","article-title":"Myotrophic activity of 19-nortestosterone and other steroids determined\nby modified levator ani muscle method","volume":"83","author":"Hershberger","year":"1953","journal-title":"Proc Soc Exp Biol Med"},{"key":"2026081311020517900_micit14","author":"Hilgar"},{"key":"2026081311020517900_micit15","author":"Hsu"},{"key":"2026081311020517900_micit16","first-page":"271","article-title":"Recherches sur la diff\u00e9renciation de l\u2019embryon de Lapin. III. R\u00f4le\ndes gonads foetales dans la diff\u00e9renciation\nseuelle","volume":"36","author":"Jost","year":"1947","journal-title":"Somat Arch Anat Microsc Morphol Exp"},{"key":"2026081311020517900_micit17","first-page":"379","article-title":"Problems of fetal endocrinology: the gonadal and hypophyseal hormones","volume":"8","author":"Jost","year":"1953","journal-title":"Rec Prog Horm Res"},{"key":"2026081311020517900_micit18","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1289\/ehp.01109785","article-title":"The OECD program to validate the rat uterotrophic bioassay to screen compounds\nfor in vivo estrogenic responses: phase 1","volume":"109","author":"Kanno","year":"2001","journal-title":"Environ Health Perspect"},{"key":"2026081311020517900_micit19","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1289\/ehp.5870","article-title":"The OECD program to validate the rat uterotrophic bioassay. Phase 2: coded\nsingle-dose studies","volume":"111","author":"Kanno","year":"2003","journal-title":"Environ Health Perspect"},{"key":"2026081311020517900_micit20","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1042\/bj0260413","article-title":"The assay of testicular hormone preparations","volume":"26","author":"Korenchevsky","year":"1932","journal-title":"Biochem J"},{"key":"2026081311020517900_micit21","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1042\/bj0261306","article-title":"The response of castrated male rats to the injection of the testicular\nhormone","volume":"26","author":"Korenchevsky","year":"1932","journal-title":"Biochem J"},{"key":"2026081311020517900_micit22","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1093\/toxsci\/56.2.389","article-title":"Cellular and molecular mechanisms of action of linuron: an antiandrogenic\nherbicide that produces reproductive malformations in male rats","volume":"56","author":"Lambright","year":"2000","journal-title":"Toxicol Sci"},{"key":"2026081311020517900_micit23","first-page":"337","article-title":"Aspects of androgen-dependent events as studied by antiandrogens","volume":"B26","author":"Neumann","year":"1970","journal-title":"Rec Prog Horm Res"},{"key":"2026081311020517900_micit24","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1210\/endo-78-3-628","article-title":"Development of a vagina in male rats by inhibiting androgen receptors with\nan anti-androgen during the critical phase of organogenesis","volume":"78","author":"Neumann","year":"1966","journal-title":"Endocrinology"},{"key":"2026081311020517900_micit25","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1093\/toxsci\/51.1.44","article-title":"Detection of the environmental antiandrogen p,p\u2019-DDE in CD and Long-Evans rats using a tier I screening battery and a Hershberger\nassay","volume":"51","author":"O\u2019Connor","year":"1999","journal-title":"Toxicol Sci"},{"key":"2026081311020517900_micit26","author":"OECD"},{"key":"2026081311020517900_micit27","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1210\/endo-94-2-532","article-title":"On the mechanism of the antiandrogenic action of flutamide (\u03b1-\u03b1-\u03b1-trifluoro-2-methyl-4\u2032-nitro-m-propionotoluidide) in the rat","volume":"94","author":"Peets","year":"1973","journal-title":"Endocrinology"},{"issue":"248","key":"2026081311020517900_micit28","first-page":"71541","article-title":"Endocrine disruptor screening program; proposed statement of policy","volume":"63","author":"U.S. EPA (U.S. Environmental Protection Agency)","year":"1998","journal-title":"Fed Reg"},{"key":"2026081311020517900_micit29","author":"U.S. EPA (U.S. Environmental Protection Agency)"},{"key":"2026081311020517900_micit30","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1093\/toxsci\/53.2.289","article-title":"Comparative evaluation of a 5-day Hershberger assay utilizing mature male\nrats and a pubertal male assay for detection of flutamide\u2019s\nantiandrogenic activity","volume":"53","author":"Yamada","year":"2000","journal-title":"Toxicol Sci"},{"key":"2026081311020517900_micit31","first-page":"25","article-title":"Time-course changes in accessory sex organ weights in male CDIGS rats after\ncastration","volume":"40","author":"Yamasaki","year":"2001","journal-title":"Cont Topics Labor Anim Sci"}],"container-title":["Environmental Health Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-pdf\/114\/8\/1259\/66529786\/ehp.8751.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-pdf\/114\/8\/1259\/66529786\/ehp.8751.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T15:04:02Z","timestamp":1786633442000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article\/114\/8\/1259\/5248522\/The-OECD-Program-to-Validate-the-Rat-Hershberger"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,2,27]]},"references-count":31,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2006,2,27]]},"published-print":{"date-parts":[[2006,8,1]]}},"URL":"https:\/\/doi.org\/10.1289\/ehp.8751","relation":{},"ISSN":["0091-6765","1552-9924"],"issn-type":[{"value":"0091-6765","type":"print"},{"value":"1552-9924","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,2,27]]}}}