Pharmacokinetics of Bisphenol A in Humans Following Dermal Administration
or U.S. Environmental Protection Agency (US EPA). 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 elimination half-life and area under the curve. RESULTS AND CONCLUSIONS: Detectable serum levels of total d6-BPA were observed at 1.4 hours 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 hours after start of dermal administration, with Cmax of 0.272 nM. The elimination half-lives of total d6-BPA and free d6-BPA were 17.9 ± 4.88 h and 14.8 ± 4.06 h, respectively. Free d6-BPA was a greater percentage of the area under the curve of total serum BPA (8.95%) compared to the 0.56% observed in our previously published oral study. Recovery of total administered d6-BPA in urine was ~1% of the applied dose after three days. Analysis of the area under the curve for dermal and oral administration revealed that 2.3% of the dermal dose became systemically available. These data confirm predictions that pharmacokinetics of BPA differ following oral and dermal exposure. Dermal exposure resulted in a longer apparent serum elimination half-life and higher free:total d6-BPA ratio compared to oral.