Format

Send to

Choose Destination
Environ Int. 2015 Oct;83:107-15. doi: 10.1016/j.envint.2015.06.008. Epub 2015 Jun 24.

Pharmacokinetics of bisphenol A in humans following a single oral administration.

Author information

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. Electronic address: thayer@niehs.nih.gov.
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. Electronic address: daniel.doerge@fda.hhs.gov.
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. Electronic address: dawnhunt2233@outlook.com.
4
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.
5
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.
6
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.
7
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.
8
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.
9
Social & Scientific Systems, Inc., 1009 Slater Rd # 120, Durham, NC 27703, USA. Electronic address: MEasterling@s-3.com.
10
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.
11
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.

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.

KEYWORDS:

ADME; Bioavailability; Deuterated bisphenol A; Endocrine disruptor; Excretion; Metabolism

PMID:
26115537
PMCID:
PMC4545316
DOI:
10.1016/j.envint.2015.06.008
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center