Serum bisphenol A pharmacokinetics and prostate neoplastic responses following oral and subcutaneous exposures in neonatal Sprague-Dawley rats

Abstract

The present study examines BPA pharmacokinetics in neonatal rats following s.c. injection or oral delivery of 10g BPA/kg BW and compares susceptibility to estrogen-induced prostate intraepithelial neoplasia (PIN) following either exposure route. Serum BPA in PND3 rats was measured using HPLC-MS-MS. Free and total BPA at Cmax were 1.77 and 2.0 ng/ml, respectively following injection and 0.26 and 1.02 ng/ml, respectively following oral exposure. The AUC0-2 for free and total BPA was 4.1- fold and 1.8-fold greater, respectively, in s.c. versus oral delivery. While exposure route affected BPA metabolism, internal dosimetry following s.c. injection of 10g BPA/kg BW is similar to BPA levels observed in humans. Prostates from aged rats given s.c. or oral BPA neonatally and T+E implants as adults exhibited nearly identical, heightened susceptibility to PIN incidence and score as compared to neonatal oil-controls. These findings on prostate health are directly relevant to humans at current BPA exposure levels.