Pharmacokinetics of bisphenol A in humans following dermal administration

Alan F Sasso; Ralph Pirow; Syam S Andra; Rebecca Church; Rebecca M Nachman; Susanne Linke; Dustin F Kapraun; Shepherd H Schurman; Manish Arora; Kristina A Thayer; John R Bucher; Linda S Birnbaum

doi:10.1016/j.envint.2020.106031

Pharmacokinetics of bisphenol A in humans following dermal administration

Environ Int. 2020 Nov:144:106031. doi: 10.1016/j.envint.2020.106031. Epub 2020 Aug 13.

Authors

Affiliations

¹ U.S. Environmental Protection Agency (US EPA), Office of Research and Development, Center for Public Health and Environmental Assessment (CPHEA), Chemical Pollutant Assessment Division (CPAD), 1200 Pennsylvania Avenue, NW (8623R), Washington, DC 20460, USA. Electronic address: Sasso.Alan@epa.gov.
² German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany. Electronic address: Ralph.Pirow@bfr.bund.de.
³ Exposure Biology, Senator Frank R. Lautenberg Environmental Health Sciences Laboratory, Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: syam.andra@mssm.edu.
⁴ Clinical Research Unit, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), P.O. Box 12233, Mail Drop CU-01, Research Triangle Park, NC 27709, USA. Electronic address: rebecca.church@nih.gov.
⁵ U.S. Environmental Protection Agency (US EPA), Office of Research and Development, Center for Public Health and Environmental Assessment (CPHEA), Chemical Pollutant Assessment Division (CPAD), 1200 Pennsylvania Avenue, NW (8623R), Washington, DC 20460, USA. Electronic address: nachman.rebecca@epa.gov.
⁶ German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany. Electronic address: Susanne.Linke@bfr.bund.de.
⁷ U.S. Environmental Protection Agency (US EPA), Office of Research and Development, Center for Public Health and Environmental Assessment (CPHEA), Chemical Pollutant Assessment Division (CPAD), 1200 Pennsylvania Avenue, NW (8623R), Washington, DC 20460, USA. Electronic address: Kapraun.Dustin@epa.gov.
⁸ Clinical Research Unit, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), P.O. Box 12233, Mail Drop CU-01, Research Triangle Park, NC 27709, USA. Electronic address: schurmansh@niehs.nih.gov.
⁹ Exposure Biology, Senator Frank R. Lautenberg Environmental Health Sciences Laboratory, Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: manish.arora@mssm.edu.
¹⁰ U.S. Environmental Protection Agency (US EPA), Office of Research and Development, Center for Public Health and Environmental Assessment (CPHEA), Chemical Pollutant Assessment Division (CPAD), 1200 Pennsylvania Avenue, NW (8623R), Washington, DC 20460, USA. Electronic address: thayer.kris@epa.gov.
¹¹ Division of the National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), P.O. Box 12233, Mail Drop K2-02, Research Triangle Park, NC 27709, USA. Electronic address: bucher@niehs.nih.gov.
¹² Division of the National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), 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 following dermal exposure.

Objective: To examine the absorption, distribution, metabolism and excretion of BPA in humans following dermal administration.

Methods: We dermally administered deuterated BPA (d6-BPA) to 10 subjects (6 men and 4 women) at a dose of 100 µg/kg over a 12-hour period and conducted blood and urine analysis from the beginning of dosing through a three- or six-day period. We present time-course serum and urine concentrations of total and unconjugated ("free") d6-BPA and used this information to calculate terminal half-life and area under the curve.

Results and conclusions: Detectable serum levels of total d6-BPA were observed at 1.4 h after the start of dosing, and a maximum serum concentration (C_max) of 3.26 nM was observed. Free d6-BPA was detectable in serum 2.8 h after start of dermal administration, with C_max of 0.272 nM. Beginning at approximately seven hours and continuing to 12 h (which corresponds to cessation of exposure), the concentration of free and total serum d6-BPA plateaued. The terminal half-lives of total d6-BPA and free d6-BPA in the body were 21.4 ± 9.81 h and 17.6 ± 7.69 h, respectively. Elimination from the body was rate-limited by kinetics in the dermal compartment. Free d6-BPA was a greater percentage of the area under the curve of total serum BPA (8.81%) compared to the 0.56% observed in our previously published oral study. Recovery of total d6-BPA in urine was <2% of the applied dose after six days. Analysis of the area under the curve for dermal and oral administration revealed that 2.2% of the dermal dose became systemically available. These data are in line with prior studies indicating how pharmacokinetics of BPA differ following oral and dermal exposures. Dermal exposure resulted in a longer apparent half-life and higher free:total d6-BPA ratio compared to oral.

Keywords: Absorption; Bioavailability; Distribution; Endocrine disruptor; Excretion; Metabolism.

MeSH terms

Administration, Cutaneous
Administration, Oral
Benzhydryl Compounds*
Female
Half-Life
Humans
Male
Phenols*

Substances

Benzhydryl Compounds
Phenols
bisphenol A

Grants and funding

EPA999999/ImEPA/Intramural EPA/United States