Metabolism and disposition of bisphenol A in female rats.
Bisphenol A (BPA), which is used in the manufacture of polycarbonates, elicits weak estrogenic activity in in vitro and in vivo test systems. The objectives of this study were to compare the patterns of disposition of radioactivity in adult female F-344 and CD rats after oral administration of (14)C BPA (100 mg/kg), to isolate the glucuronide of BPA and to assess its estrogenic activity in vitro, and to evaluate the transfer of radioactivity to pups from lactating dams administered (14)C BPA. Over 6 days, F-344 rats excreted more radioactivity in urine than CD rats. The major metabolite in urine was identified as bisphenol A glucuronide (BPA gluc) by incubation with beta-glucuronidase and (1)H and (13)C NMR spectroscopy. In lactating CD rats administered (14)C 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 microg equiv/ml (mean +/- SD) from dams collected 1, 8, and 26 h after dosing, respectively. Radioactivity in pup carcasses indicated exposure in the range 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 at 24 h. BPA gluc was the prominent metabolite in milk and plasma. In test systems for activation of in vitro estrogen receptors alpha and beta, BPA gluc did not show appreciable efficacy at concentrations up to 0.03 mM, indicating that metabolism via glucuronidation is a detoxication reaction.
Snyder
R W
RW
Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709, USA.
Maness
S C
SC
Gaido
K W
KW
Welsch
F
F
Sumner
S C
SC
Fennell
T R
TR
D000395:Air Pollutants, Occupational / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D001559:Benzhydryl Compounds; D002851:Chromatography, High Pressure Liquid; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D020719:Glucuronides / Q000378:metabolism; D007774:Lactation / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D010636:Phenols / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014162:Transfection; D000098826:Bisphenol A Compounds
D000395:Air Pollutants, Occupational; D001559:Benzhydryl Compounds; D004965:Estrogen Antagonists; D005966:Glucuronidase; D020719:Glucuronides; D008156:Luciferases; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds