Pharmacokinetics of Bisphenol A in Humans Following Dermal Administration

Abstract

Background Human exposures to bisphenol A (BPA) are widespread. Sources include food packaging and cash register receipts. Assessments of human health risk from BPA exposure rely on pharmacokinetic data for estimation of internal dose following human exposure. We addressed uncertainties regarding human pharmacokinetics of BPA following dermal exposure through an examination of absorption, distribution, metabolism and excretion in humans following dermal administration. Methods We dermally administered deuterated BPA (d6-BPA) to 10 subjects (6 men, 4 women) at a dose of 100 µg/kg over a 12-hour period and collected blood and urine samples over a follow-up period of three or six days. Using total and unconjugated (“free”) d6-BPA concentrations in serum, we calculated the elimination half-life and area under the curve. Results Detectable serum levels of total d6-BPA and unconjugated BPA were observed at 1.4 hours and 2.8 hours, respectively, after start of dermal administration, with maximum serum concentrations (Cmax) of 3.26 nM and 0.272 nM, respectively. Beginning at approximately seven hours and continuing to 12 hours, the rate of increase in free and total serum d6-BPA slowed. 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. Unconjugated d6-BPA was a greater percentage of the area under the curve of total serum BPA (8.95%) compared to 0.56% 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 2.3% of the dermal dose became systemically available. Conclusions 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. This abstract does not represent EPA policy.