Metabolism and disposition of bisphenol A in female rats

Bisphenol A (BPA), which is used in the manufacture of polycarbonates, elic its weak estrogenic activity in in vitro and in vivo test systems. The obje ctives of this study were to compare the patterns of disposition of radioac tivity in adult female F-344 and CD rats after oral administration of C-14 BPA (100 mg/kg), to isolate the glucuronide of BPA and to assess its estrog enic activity in vitro, and to evaluate the transfer of radioactivity to pu ps from lactating darns administered C-14 BPA. Over 6 days, F-344 rats excr eted more radioactivity in urine than CD rats. The major metabolite in urin e was identified as bisphenol A glucuronide (BPA glue) by incubation with p -glucuronidase and H-1 and C-13 NMR spectroscopy. In lactating CD rats admi nistered C-14 BPA (100 mg/kg) by gavage, only a small fraction of the label was found in milk, with 0.95 +/- 0.66, 0.63 +/- 0.13, and 0.26 +/- 0.10 mu g equiv/ml (mean +/- SD) from darns collected I, 8, and 26 h after dosing, respectively. Radioactivity in pup carcasses indicated exposure in the rang e of microgram equivalents per kilogram; those values ranged from 44.3 +/- 24.4 for pups separated from their lactating dams at 2 h to 78.4 +/- 10.9 a t 24 h. BPA glue was the prominent metabolite in milk and plasma. In test s ystems for activation of in vitro estrogen receptors alpha and beta, BPA gl ue did not show appreciable efficacy at concentrations up to 0.03 mM, indic ating that metabolism via glucuronidation is a detoxication reaction. (C) 2 000 Academic Press.