[P2-61] Oral Exposure of Female Rhesus Monkeys to 8-Times More Bisphenol A Than the FDAs Safe Daily Dose Results in Plasma Unconjugated Bisphenol A below Mean Levels in People.

CA VandeVoort, JA Taylor, PA Hunt, WV Welshons, FS Vom Saal, California Natl Primate Res Ctr, Univ of California, Davis, CA; Biol Scis, Univ of Missouri, Columbia, MO; Molecular Bioscis, Washington State Univ, Pullman, WA; Biomed Scis, Univ of Missouri, Columbia, MO

Estimates of daily adult human exposure to the estrogenic endocrine disrupting chemical bisphenol A (BPA) in the USA have ranged from below 1 g/kg to over 500 g/kg; the latter is 10-fold higher than the FDA current estimated safe daily intake dose of 50 g/kg. Those proposing low human exposure also claim virtually complete first pass conjugation (inactivation) in the liver after BPA absorption from the gut (the assumption being that virtually all human exposure is from food and beverages). However, this prediction is inconsistent with data from numerous studies that report mean levels of unconjugated (biologically active) BPA in people living in developed countries ranging from about 0.5 4 ng/ml, regardless of analytical method (1). Since the rhesus monkey historically has been a good model for human metabolism of chemicals such as BPA, we fed 5 adult female rhesus macaques (Macaca mulatta) a 400-g/kg dose of deuterated bisphenol A (dBPA). Blood was collected prior to and during the following 24 h, and serum dBPA was analyzed by isotope dilution LC-MS (0.2 ng/ml limit of detection). The maximum serum unconjugated dBPA concentration (CMax) of 4.51.2 ng/ml (meanSEM) was reached in 1 hr. The mean area under the curve for 24 h (AUC0-24/24) was 0.48 ng/ml. The half-life for clearance between 1 12 hr (when the slope on a semi-log plot was linear) was 1.0 h. At 12 h serum unconjugated dBPA was 0.10.03 ng/ml, and at 24 hr unconjugated dBPA was below the limit of detection (we thus did not estimate the slope after 12 h). Initial findings are that unconjugated dBPA is about 3% of conjugated (glucuronidated and sulfated) dBPA, which is cleared primarily in the urine. Since no difference in the 24 h serum levels of dBPA were found after 1 or 7 days of feeding dBPA (data not shown), our findings indicate that BPA does not bioaccumulate. However, this study shows that female monkeys administered a single oral BPA dose 8-fold higher than the current estimated safe human dose showed mean serum levels of unconjugated BPA during the 24 h after administration that are exceeded by mean serum levels in human populations that have been examined. We predict that higher human exposure to BPA than regulatory agencies have estimated occurs from multiple unknown routes, in addition to known sources such as food packaging, carbonless paper, water pipes and polyvinylchloride products, since over 8-billion pounds of BPA are used to manufacture products each year.

(1) Vandenberg LN et al., Reprod Toxicol 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