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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)




  • GA Knudsen
  • JM Sanders
  • AM Sadik
  • LS Birnbaum


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.

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