Pharmacokinetics of bisphenol A in humans following dermal administration. (November 2020)

• Record Type: Journal Article
• Authors: Sasso, Alan F.; Pirow, Ralph; Andra, Syam S.; Church, Rebecca; Nachman, Rebecca M.; Linke, Susanne; Kapraun, Dustin F.; Schurman, Shepherd H.; Arora, Manish; Thayer, Kristina A.; Bucher, John R.; Birnbaum, Linda S.
• Is Part Of: Environment international. Volume 144(2020)
• Publication Date: 2020-11
• Subjects: Absorption -- Distribution -- Bioavailability -- Endocrine disruptor -- Excretion -- Metabolism; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2020.106031
• Languages: English
• ISSNs: 0160-4120

Abstract

Highlights: We dermally administered deuterated BPA to 10 subjects at 100 µg/kg over 12 h. We conducted blood and urine analysis from the beginning of dosing through 3–6 days. We present time-course serum and urine concentrations of total and free d6-BPA. Free d6-BPA was a greater percentage of total serum BPA when compared to oral data. Dermal exposure resulted in a longer half-life when compared to oral data. Approximately 2.2% of the dermal dose became systemically available. 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 (Cmax ) of 3.26 nM was observed. Free d6-BPA was detectable in serum 2.8 h after start of dermal administration, with Cmax 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.