Pharmacokinetics of bisphenol A in humans following a single oral administration |
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| Institution: | 1. 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;2. 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;3. 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;4. Biostatistics Branch, National Institute of Environmental Health Sciences, P.O. Box 12233, Mail Drop A3-03, Research Triangle Park, NC 27709, USA;5. Social & Scientific Systems, Inc., 1009 Slater Rd # 120, Durham, NC 27703, USA;6. 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;1. Exposure Biology, Lautenberg Environmental Health Sciences Laboratory, Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;2. College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China |
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| Abstract: | BackgroundHuman exposures to bisphenol A (BPA) are widespread. The current study addresses uncertainties regarding human pharmacokinetics of BPA.ObjectiveTo reduce uncertainties about the metabolism and excretion of BPA in humans following oral administration.MethodsWe 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.ResultsMean serum total (unconjugated and conjugated) d6-BPA Cmax of 1711 nM (390 ng/ml) was observed at Tmax of 1.1 ± 0.50 h. 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 ± 2.6 h, respectively. Recovery of total administered d6-BPA in urine was 84–109%. Most subjects (10 of 14) excreted > 90% as metabolites within 24 h.ConclusionsUsing 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 24 h. |
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