1. Pharmacokinetics of Bisphenol A in Humans Following Dermal Administration
- Author
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Dustin F. Kapraun, Ralph Pirow, Alan F. Sasso, John R. Bucher, Susanne Linke, Rebecca Church, Shepherd H. Schurman, Rebecca M. Nachman, Kristina A. Thayer, Linda S. Birnbaum, Manish Arora, and Syam S. Andra
- Subjects
Male ,endocrine system ,Bioavailability ,010504 meteorology & atmospheric sciences ,Excretion ,Cmax ,Administration, Oral ,Physiology ,Absorption (skin) ,Urine ,Distribution ,010501 environmental sciences ,Administration, Cutaneous ,01 natural sciences ,Absorption ,Phenols ,Pharmacokinetics ,Oral administration ,Humans ,Medicine ,Distribution (pharmacology) ,Benzhydryl Compounds ,lcsh:Environmental sciences ,0105 earth and related environmental sciences ,General Environmental Science ,lcsh:GE1-350 ,urogenital system ,business.industry ,Area under the curve ,Metabolism ,Endocrine disruptor ,General Earth and Planetary Sciences ,Female ,business ,hormones, hormone substitutes, and hormone antagonists ,Half-Life - 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
- Published
- 2020
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