Maternal and fetal pharmacokinetics of oral radiolabeled and authentic bisphenol A in the rhesus monkey
2016
Vandevoort, Catherine A. | Gerona, Roy R. | Vom Saal, Frederick S. | Tarantal, Alice F. | Hunt, Patricia A. | Hillenweck, Anne | Zalko, Daniel | Department of Obstetrics and Gynecology ; Helsinki University Hospital [Finland] (HUS) | California National Primate Research Center ; University of California [Davis] (UC Davis) ; University of California (UC)-University of California (UC) | Department of Obstetrics, Gynecology and Reproductive Sciences ; Yale University [New Haven]-Yale School of Medicine [New Haven, Connecticut] (YSM) | School of Biological Sciences [Univ California San Diego] (UC San Diego) ; University of California [San Diego] (UC San Diego) ; University of California (UC)-University of California (UC) | School of Medicine, Departments of Pediatrics and Cell Biology and Human Anatomy ; University of California [Davis] (UC Davis) ; University of California (UC)-University of California (UC) | School of Molecular Biosciences ; Washington State University (WSU) | Métabolisme et Xénobiotiques (ToxAlim-MeX) ; ToxAlim (ToxAlim) ; Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT) | This work was supported by National Institute of Environmental Health Sciences (NIEHS) Grants ES016770 and the CNPRC Base Grant (National Institutes of Health) OD011107 (RR00169)
The present study was conducted in pregnant rhesus monkeys to determine the rapidity and extent to which BPA reaches the fetal compartment following oral ingestion, and the 24-hr fate of BPA. To assess metabolism changes during the course of pregnancy, we compared BPA biotransformation during the second and third trimesters in the same animals, measuring the levels of sulfated, gluronidated, and free BPA in maternal serum, amniotic fluid, and fetal serum. All animals showed measurable unconjugated and conjugated BPA in the fetal compartment and slow clearance compared to maternal serum. There were higher levels of BPA-G in amniotic fluid at 150 days gestation compared to 100 days gestation, as well as higher levels of BPA-G than BPA-S. We also monitored H-3-BPA (and metabolites) in key tissues and excreta from a mother and fetus and from a non-pregnant female. The elimination of radioactivity was rapid, but residues were still detectable 24 hr after dosing in all tissues analyzed. These data suggest that, in primates, rapid maternal processing of BPA does not alleviate the risk of exposure to the developing fetus. This study elevates concerns about levels of current BPA human exposure from potentially a large number of unknown sources and the risks posed to developing fetuses.
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