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Juvenile Toxicity Rodent Model to Study Toxicological Effects of Bisphenol A (BPA) at Dose Levels Derived From Italian Children Biomonitoring Study.
Tassinari, Roberta; Narciso, Laura; Tait, Sabrina; Busani, Luca; Martinelli, Andrea; Di Virgilio, Antonio; Carli, Fabrizia; Deodati, Annalisa; La Rocca, Cinzia; Maranghi, Francesca.
Afiliación
  • Tassinari R; Center for Gender-Specific Medicine.
  • Narciso L; Center for Gender-Specific Medicine.
  • Tait S; Center for Gender-Specific Medicine.
  • Busani L; Department of Infectious Diseases.
  • Martinelli A; Experimental Animal Welfare Sector, Istituto Superiore di Sanità, 00161 Rome, Italy.
  • Di Virgilio A; Experimental Animal Welfare Sector, Istituto Superiore di Sanità, 00161 Rome, Italy.
  • Carli F; Institute of Clinical Physiology, National Research Council, Pisa, Italy.
  • Deodati A; Dipartimento Pediatrico Universitario Ospedaliero "Bambino Gesù".
  • La Rocca C; Children's Hospital-Tor Vergata University, Rome, Italy.
  • Maranghi F; Center for Gender-Specific Medicine.
Toxicol Sci ; 173(2): 387-401, 2020 02 01.
Article en En | MEDLINE | ID: mdl-31697385
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-olive 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenoles / Compuestos de Bencidrilo / Hormonas Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Toxicol Sci Asunto de la revista: TOXICOLOGIA Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenoles / Compuestos de Bencidrilo / Hormonas Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Toxicol Sci Asunto de la revista: TOXICOLOGIA Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos