title: 24-hour human urine and serum profiles of bisphenol A: Evidence against sublingual absorption following ingestion in soup.
abstract: Extensive first-pass metabolism of ingested bisphenol A (BPA) in the gastro-intestinal tract and liver restricts blood concentrations of bioactive BPA to <1% of total BPA in humans and non-human primates. Absorption of ingested BPA through non-metabolizing tissues of the oral cavity, recently demonstrated in dogs, could lead to the higher serum BPA concentrations reported in some human biomonitoring studies. We hypothesized that the extensive interaction with the oral mucosa by a liquid matrix, like soup, relative to solid food or capsules, might enhance absorption through non-metabolizing oral cavity tissues in humans, producing higher bioavailability and higher serum BPA concentrations. Concurrent serum and urine concentrations of d6-BPA, and its glucuronide and sulfate conjugates, were measured over a 24hour period in 10 adult male volunteers following ingestion of 30μg d6-BPA/kg body weight in soup. Absorption of d6-BPA was rapid (t1/2=0.45h) and elimination of the administered dose was complete 24h post-ingestion, evidence against any tissue depot for BPA. The maximum serum d6-BPA concentration was 0.43nM at 1.6h after administration and represented <0.3% of total d6-BPA. Pharmacokinetic parameters, pharmacokinetic model simulations, and the significantly faster appearance half-life of d6-BPA-glucuronide compared to d6-BPA (0.29h vs 0.45h) were evidence against meaningful absorption of BPA in humans through any non-metabolizing tissue (<1%). This study confirms that typical exposure to BPA in food produces picomolar to subpicomolar serum BPA concentrations in humans, not nM concentrations reported in some biomonitoring studies.
authors.affiliation: Health Effects and Exposure Science, Pacific Northwest National Laboratory, Richland, WA 99352, USA; Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 93771, USA. Electronic address: jt@pnl.gov.
authors.forename: Justin G
authors.initials: JG
authors.lastname: Teeguarden
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA. Electronic address: nathan.twaddle@fda.hhs.gov.
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Twaddle
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA. Electronic address: mona.churchwell@fda.hhs.gov.
authors.forename: Mona I
authors.initials: MI
authors.lastname: Churchwell
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA. Electronic address: xiaoxia.yang@fda.hhs.gov.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Yang
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA. Electronic address: jeffrey.fisher@fda.hhs.gov.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Fisher
authors.affiliation: Division of Epidemiology, College of Public Health, The Ohio State University, Columbus, OH 43210, USA. Electronic address: seryak.2@osu.edu.
authors.forename: Liesel M
authors.initials: LM
authors.lastname: Seryak
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA. Electronic address: daniel.doerge@fda.hhs.gov.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Doerge
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine; D001711:Biotransformation; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D005506:Food Contamination; D020719:Glucuronides / Q000097:blood / Q000652:urine; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D009061:Mouth Mucosa / Q000378:metabolism*; D065568:Oral Mucosal Absorption; D010636:Phenols / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine; D065667:Renal Elimination; D013431:Sulfates / Q000097:blood / Q000652:urine; D055815:Young Adult; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D020719:Glucuronides; D010636:Phenols; D013431:Sulfates; C512161:bisphenol A glucuronide; D000098826:Bisphenol A Compounds; C006780:bisphenol A
keywords: Bisphenol A; Endocrine disruptors; Exposure; Oral; Pharmacokinetics; Sublingual