[P2-66] Serum Bisphenol A Concentrations Following Oral Adminstration in Adult Female CD-1 Mice.

JA Taylor, WV Welshons, CA VandeVoort, FS vom Saal, Biol Scis, Univ of Missouri, Columbia, MO; Biomed Scis, Univ of Missouri, Columbia, MO; California Natl Primate Res Ctr, Univ of California, Davis, CA

Bisphenol A (BPA) present in food and beverages is considered the main source of human exposure to this estrogenic endocrine disrupting chemical. It has been proposed that ingestion of BPA is safe due to virtually complete first pass conjugation in the liver after BPA absorption from the gut and consequent excretion. There is controversy regarding daily human exposure to BPA, with estimates ranging from below 1 g/kg to over 500 g/kg, However, the estimates of very low daily human exposure to BPA are at odds with data that report average BPA levels in blood ranging from 0.5-4 ng/ml (L. Vandenberg et al. Reprod. Toxicol. 24:139, 2007). In this study we examined the serum concentrations of BPA in young adult female CD-1 mice prior to and during the 24 h following a single 100 mg/kg oral dose of BPA. Serum from four mice at each of 7 time points was pooled, and separate aliquots were used for unconjugated (bioactive) BPA and conjugated (glucuronidated and sulfated) BPA measurements. BPA was analyzed by HPLC with CoulArray detection (0.25 ng/ml limit of detection). The maximum serum unconjugated BPA concentration (CMax) of 831 ng/ml was reached in 1 hr. The mean area under the curve for 24 h (AUC0-24/24) was 118 ng/ml. Unconjugated BPA concentrations at 6 h and 24 h were 98 ng/ml and 23 ng/ml respectively. Conjugated BPA values followed a similar time course to that for unconjugated BPA, with maximum value of 101 g/ml reached at 1 hour, and values at 6 h and 24 h of 15 g/ml and 0.42 g/ml respectively. These initial findings indicate that the ratio of unconjugated to conjugated serum BPA levels in mice is 1:100. The 100 mg/kg dose of BPA was chosen for this stud to allow detection by CoulArray throughout the 24 h after administration. However, our prior data indicate that serum concentrations of unconjugated BPA are approximately linear with administered oral dose. Based on the assumption of linearity, dividing the serum BPA values determined at 100 mg/kg by 250 brings these data to concentrations comparable to those seen in non-pregnant adult female rhesus macaques dosed at 400 ug/kg. This suggests that the mouse may be an appropriate model for estimating blood levels of bioactive BPA in response to a comparable oral dose in monkeys and thus possibly humans. Ongoing experiments are testing this hypothesis using radiolabeled BPA fed to female CD-1 mice at the 400 ug/kg dose for comparison to both primate data and other mouse data.

(1) Vandenburg LN et al., Reproductive Toxicology 2007; 24:139

Supported by NIEHS.

Date: Thursday, June 11, 2009
Session Info: POSTER SESSION: BASIC/TRANSLATIONAL - Endocrine Disrupting Chemicals I (1:30 PM-3:30 PM)
Presentation Time: 1:30 PM
Room: Halls A & B