October 9 - 12, 2012
Building 10 & Natcher Conference Center
- General Schedule of Events
- Opening Plenary Session
- Concurrent Symposia Sessions
- Poster Sessions
- National Graduate Student Research Conference
- FARE Award Ceremony
- Special Exhibits on Resources for Intramural Research
- TSA Research Festival Exhibit Show
- Clinical Center Tours
- Research Festival Committees
- Past Research Festivals
Disposition and kinetics of Tetrabromobisphenol A in female Wistar-Han rats
| Thursday, November 07, 2013 — Poster Session II | |||
|---|---|---|---|
12:00 p.m. – 2:00 p.m. |
FAES Academic Center (Upper-Level Terrace) |
NCI |
CHEMCELL-9 |
Authors
- GA Knudsen
- JM Sanders
- AM Sadik
- LS Birnbaum
Abstract
Tetrabromobisphenol A (TBBPA) is the brominated flame retardant with the largest production volume worldwide. It is used in printed circuit boards, plastic casings, and laminates. NIEHS-NTP 2-year bioassays found dose-dependent increases in uterine tumor formation in female Wistar-Han rats following TBBPA exposures. To characterize this sex-dependent toxicity, the disposition and toxicokinetic profile of TBBPA were investigated using female Wistar-Han rats. The primary route of elimination following [14C]-TBBPA oral administration (25, 250 or 1,000 mg/kg) was in feces (94-98% in feces, 0.2-2% in urine, <0.1% in tissues by 72h). Free TBBPA in plasma was used to estimate kinetics; rapid absorption with an observed Cmax at 1.5h post-dose and a prolonged distribution phase were observed after oral dosing (250 mg/kg). TBBPA concentrations decreased rapidly after an IV dose (25 mg/kg) followed by a long distribution phase, with 2% of the dose remaining at 6h. These results indicate low systemic bioavailability for TBBPA (F<5%) with potential for enterohepatic cycling, similar to previous reports for male rats. A single administration of the highest dose appeared to saturate elimination pathways; following chronic high exposures, TBBPA may compete with endogenous substrates for metabolism in extrahepatic tissues (e.g., estrogen sulfation by SULT1E1) resulting in endocrine disruption.
