title: Pharmacokinetics of bisphenol A in humans following a single oral administration.
abstract: BACKGROUND
  Human exposures to bisphenol A (BPA) are widespread. The current study addresses uncertainties regarding human pharmacokinetics of BPA.
  
  
  OBJECTIVE
  To reduce uncertainties about the metabolism and excretion of BPA in humans following oral administration.
  
  
  METHODS
  We exposed six men and eight women to 100 μg/kg bw of deuterated BPA (d6-BPA) by oral administration and conducted blood and urine analysis over a three day period. The use of d6-BPA allowed administered d6-BPA to be distinguished from background native (unlabeled) BPA. We calculated the rate of oral absorption, serum elimination, half-life, area under the curve (AUC), urinary excretion, and metabolism to glucuronide and sulfate conjugates.
  
  
  RESULTS
  Mean serum total (unconjugated and conjugated) d6-BPA Cmax of 1711 nM (390 ng/ml) was observed at Tmax of 1.1 ± 0.50h. Unconjugated d6-BPA appeared in serum within 5-20 min of dosing with a mean Cmax of 6.5 nM (1.5 ng/ml) observed at Tmax of 1.3 ± 0.52 h. Detectable blood levels of unconjugated or total d6-BPA were observed at 48 h in some subjects at concentrations near the LOD (0.001-0.002 ng/ml). The half-times for terminal elimination of total d6-BPA and unconjugated d6-BPA were 6.4 ± 2.0 h and 6.2 ± 2.6h, respectively. Recovery of total administered d6-BPA in urine was 84-109%. Most subjects (10 of 14) excreted >90% as metabolites within 24h.
  
  
  CONCLUSIONS
  Using more sensitive methods, our study expands the findings of other human oral pharmacokinetic studies. Conjugation reactions are rapid and nearly complete with unconjugated BPA comprising less than 1% of the total d6-BPA in blood at all times. Elimination of conjugates into urine largely occurs within 24h.
authors.affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, P.O. Box 12233, Mail Drop K2-02, Research Triangle Park, NC 27709, USA. Electronic address: thayer@niehs.nih.gov.
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Thayer
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food & Drug Administration, NCTR-53C RM204L HFT-110, 3900 NCTR Road, Jefferson, AR 72079, USA. Electronic address: daniel.doerge@fda.hhs.gov.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Doerge
authors.affiliation: Clinical Research Unit, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, P.O. Box 12233, Mail Drop CU-01, Research Triangle Park, NC 27709, USA. Electronic address: dawnhunt2233@outlook.com.
authors.forename: Dawn
authors.initials: D
authors.lastname: Hunt
authors.affiliation: Clinical Research Unit, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, P.O. Box 12233, Mail Drop CU-01, Research Triangle Park, NC 27709, USA. Electronic address: schurmansh@niehs.nih.gov.
authors.forename: Shepherd H
authors.initials: SH
authors.lastname: Schurman
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food & Drug Administration, NCTR-53C RM204L HFT-110, 3900 NCTR Road, 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 & Drug Administration, NCTR-53C RM204L HFT-110, 3900 NCTR Road, Jefferson, AR 72079, USA. Electronic address: Mona.Churchwell@fda.hhs.gov.
authors.forename: Mona I
authors.initials: MI
authors.lastname: Churchwell
authors.affiliation: Clinical Research Unit, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, P.O. Box 12233, Mail Drop CU-01, Research Triangle Park, NC 27709, USA. Electronic address: garantziotis@niehs.nih.gov.
authors.forename: Stavros
authors.initials: S
authors.lastname: Garantziotis
authors.affiliation: Biostatistics Branch, National Institute of Environmental Health Sciences, P.O. Box 12233, Mail Drop A3-03, Research Triangle Park, NC 27709, USA. Electronic address: kissling@niehs.nih.gov.
authors.forename: Grace E
authors.initials: GE
authors.lastname: Kissling
authors.affiliation: Social & Scientific Systems, Inc., 1009 Slater Rd # 120, Durham, NC 27703, USA. Electronic address: MEasterling@s-3.com.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Easterling
authors.affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, P.O. Box 12233, Mail Drop K2-02, Research Triangle Park, NC 27709, USA. Electronic address: bucher@niehs.nih.gov.
authors.forename: John R
authors.initials: JR
authors.lastname: Bucher
authors.affiliation: National Cancer Institute, National Institutes of Health, Department of Health and Human Services, P.O. Box 12233, Mail Drop B2-01, Research Triangle Park, NC 27709, USA. Electronic address: birnbaumls@niehs.nih.gov.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Birnbaum
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001559:Benzhydryl Compounds / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D004785:Environmental Pollutants / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D005260:Female; D020719:Glucuronides / Q000097:blood / Q000652:urine; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009657:North Carolina; D010636:Phenols / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D013463:Sulfuric Acid Esters / Q000097:blood / Q000652:urine; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D020719:Glucuronides; D010636:Phenols; D013463:Sulfuric Acid Esters; C512161:bisphenol A glucuronide; D000098826:Bisphenol A Compounds; C006780:bisphenol A
keywords: ADME; Bioavailability; Deuterated bisphenol A; Endocrine disruptor; Excretion; Metabolism