{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:19:49Z","timestamp":1787167189947,"version":"build-2736575974"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T00:00:00Z","timestamp":1573084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"European Commission Directorate General Environment in the LIFE+ Programme"},{"name":"Environment Policy and Governance","award":["LIFE13 ENV\/IT\/000482"],"award-info":[{"award-number":["LIFE13 ENV\/IT\/000482"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Bisphenol A (BPA) is a plasticizer with endocrine disrupting properties particularly relevant for children health. Recently BPA has been associated with metabolic dysfunctions but no data are yet available in specific, long-term studies. This study aimed to evaluate BPA modes of action and hazards during animal juvenile life-stage, corresponding to childhood. Immature Sprague-Dawley rats of both sexes were orally treated with 0 (vehicle only\u2014olive oil), 2, 6, and 18 mg\/kg bw per day of BPA for 28 days, from weaning to sexual maturity. Dose levels were obtained from the PERSUADED biomonitoring study in Italian children. Both no-observed-adverse-effect-level (NOAEL)\/low-observed-adverse-effect-level (LOAEL) and estimated benchmark dose (BMD) approaches were applied. General toxicity, parameters of sexual development, endocrine\/reproductive\/functional liver and kidney biomarkers, histopathology of target tissues, and gene expression in hypothalamic-pituitary area and liver were studied. No mortality or general toxicity occurred. Sex-specific alterations were observed in liver, thyroid, spleen, leptin\/adiponectin serum levels, and hypothalamic-pituitary gene expression. Thyroid homeostasis and liver were the most sensitive targets of BPA exposure in the peripubertal phase. The proposed LOAEL was 2 mg\/kg bw, considering as critical effect the liver endpoints, kidney weight in male and adrenal histomorphometrical alterations and osteopontin upregulation in female rats. The BMD lower bounds were 0.05 and 1.33 mg\/kg bw in males and females, considering liver and thyroid biomarkers, respectively. Overall, BPA evaluation at dose levels derived from children biomonitoring study allowed to identify sex-specific, targeted toxicological effects that may have significant impact on risk assessment for children.<\/jats:p>","DOI":"10.1093\/toxsci\/kfz226","type":"journal-article","created":{"date-parts":[[2019,11,6]],"date-time":"2019-11-06T15:10:52Z","timestamp":1573053052000},"page":"387-401","source":"Crossref","is-referenced-by-count":17,"title":["Juvenile Toxicity Rodent Model to Study Toxicological Effects of Bisphenol A (BPA) at Dose Levels Derived From Italian Children Biomonitoring Study"],"prefix":"10.1093","volume":"173","author":[{"given":"Roberta","family":"Tassinari","sequence":"first","affiliation":[{"name":"Center for Gender-Specific Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Narciso","sequence":"first","affiliation":[{"name":"Center for Gender-Specific Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Tait","sequence":"first","affiliation":[{"name":"Center for Gender-Specific Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Busani","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Martinelli","sequence":"first","affiliation":[{"name":"Experimental Animal Welfare Sector, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Di Virgilio","sequence":"first","affiliation":[{"name":"Experimental Animal Welfare Sector, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizia","family":"Carli","sequence":"first","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Deodati","sequence":"first","affiliation":[{"name":"Dipartimento Pediatrico Universitario Ospedaliero \u201cBambino Ges\u00f9\u201d"},{"name":"Children\u2019s Hospital-Tor Vergata University, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"La Rocca","sequence":"first","affiliation":[{"name":"Center for Gender-Specific Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Maranghi","sequence":"first","affiliation":[{"name":"Center for Gender-Specific Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"LIFE PERSUADED Project Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Valeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Romana","family":"Mancini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Cianfarani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Germani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Gastaldelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziano","family":"Barsotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demetrio","family":"Ciociaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica Della","family":"Latta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziella","family":"Distante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melania","family":"Gaggini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Landi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Toffol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,11,7]]},"reference":[{"key":"2020030307494698500_kfz226-B1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.reprotox.2018.05.002","article-title":"Perinatal BPA exposure and reproductive axis function in CD-1 mice","volume":"79","author":"Acevedo","year":"2018","journal-title":"Reprod. 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