Journal
ENVIRONMENTAL HEALTH PERSPECTIVES
Volume 121, Issue 8, Pages 951-956Publisher
US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
DOI: 10.1289/ehp.1206339
Keywords
bioavailability; bisphenol A; endocrine disruptor; pharmacokinetic analysis; sublingual exposure
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BACKGROUND: Bisphenol A (BPA) risk assessment is currently hindered by the rejection of reported higher-than-expected plasma BPA concentrations in humans after oral ingestion. These are deemed incompatible with the almost complete hepatic first-pass metabolism of BPA into its inactive glucurono-conjugated form, BPA glucuronide (BPAG). OBJECTIVES: Using dogs as a valid model, we compared plasma concentrations of BPA over a 24-hr period after intravenous, orogastric, and sub-lingual administration in order to establish the absolute bioavailability of BPA administered sub-lingually and to compare it with oral bioavailability. METHODS: Six dogs were sublingually administered BPA at 0.05 mg/kg and 5 mg/kg. We compared the time course of plasma BPA concentrations with that obtained in the same dogs after intravenous administration of the same BPA doses and after a 20-mg/kg BPA dose administrated by orogastric gavage. RESULTS: The data indicated that the systemic bioavailability of BPA deposited sublingually was high (70-90%) and that BPA transmucosal absorption from the oral cavity led to much higher BPA internal exposure than obtained for BPA absorption from the gastro-intestinal tract. The concentration ratio of BPAG to BPA in plasma was approximately 100-fold lower following sub-lingual administration than after orogastric dosing, distinguishing the two pathways of absorption. CONCLUSIONS: Our findings demonstrate that BPA can be efficiently and very rapidly absorbed through the oral mucosa after sub-lingual exposure. This efficient systemic entry route of BPA may lead to far higher BPA internal exposures than known for BPA absorption from the gastro-intestinal tract.
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