Disposition and kinetics of tetrabromobisphenol A in female Wistar Han rats

Publication date: 2014 Source:Toxicology Reports, Volume 1 Author(s): Gabriel A. Knudsen , J. Michael Sanders , Abdella M. Sadik , Linda S. Birnbaum Tetrabromobisphenol A (TBBPA) is the brominated flame retardant with the largest production volume worldwide. NTP 2-year bioassays found TBBPA dose-dependent increases in uterine tumors in female Wistar Han rats; evidence of reproductive tissues carcinogenicity was equivocal in male rats. To explain this apparent sex-dependence, the disposition and toxicokinetic profile of TBBPA were investigated using female Wistar Han rats, as no data were available for female rats. In these studies, the primary route of elimination following [14C]-TBBPA administration (25, 250 or 1000mg/kg) was in feces; recoveries in 72h were 95.7±3.5%, 94.3±3.6% and 98.8±2.2%, respectively (urine: 0.2–2%; tissues: <0.1). TBBPA was conjugated to mono-glucuronide and -sulfate metabolites and eliminated in the bile. Plasma toxicokinetic parameters for a 250mg/kg dose were estimated based on free TBBPA, as determined by UV/radiometric-HPLC analyses. Oral dosing by gavage (250mg/kg) resulted in a rapid absorption of compound into the systemic circulation with an observed C max at 1.5h post-dose followed by a prolonged terminal phase. TBBPA concentrations in plasma decreased rapidly after an IV dose (25mg/kg) followed by a long elimination phase. These results indicate low systemic bioavailability (F <0.05), similar to previous reports u...
Source: Toxicology Reports - Category: Toxicology Source Type: research