Comparison of Serum Bisphenol A Concentrations in Mice Exposed to Bisphenol A through the Diet versus Oral Bolus Exposure

Background: Bisphenol A (BPA) is a widely produced endocrine-disrupting chemical. Diet is a primary route of exposure, but internal exposure (serum concentrations) in animals and humans has been measured only after single oral bolus administration. Objective: We compared serum concentrations of BPA over a 24-hr period after oral bolus administration or ad libitum feeding in mice and assessed for buildup with dietary exposure. Methods: Adult female mice were administered [dimethyl-d(6)]-BPA (BPA-d(6)) as a single oral bolus (20 mg/kg body weight) or fed a diet containing 100 mg BPA-d(6)/kg feed weight ad libitum for 1 week. Serum concentrations were analyzed using isotope dilution liquid chromatography coupled with electrospray tandem mass spectrometry and compared between exposure groups over the first 23 hr and after 7 days of dietary exposure. Results: Maximum concentration (C(max)) for BPA-d(6) during the first 24 hr was reached at 1 hr and 6 hr for oral bolus and diet groups, respectively. Relative BPA-d(6) bioavailability (unconjugated BPA-d(6)) was higher in diet-exposed mice than in the bolus group despite a relative lower absorption, a phenomenon consistent with an inhibitory effect of food on first-pass hepatic metabolism. In mice with ongoing dietary exposure, unconjugated BPA-d(6) was higher on day 7 than on day 1. Conclusions: This is the first report of serum BPA concentrations in an animal model exposed to this chemical via the diet. Although bolus administration of BPA-d(6) led to peak concentrations within 1 hr, C(max) for diet-exposed mice was delayed for several hours. However, bolus administration underestimates bioavailable serum BPA concentrations in animals—and presumably humans—than would result from dietary exposure. Exposure via diet is a more natural continuous exposure route than oral bolus exposure and is thus a better predictor of BPA concentrations in chronically exposed animals and humans.