چکیده (انگلیسی):

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 1000 mg/kg) was in feces; recoveries in 72 h
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 250 mg/kg dose were estimated based on free
TBBPA, as determined by UV/radiometric-HPLC analyses. Oral dosing by gavage (250 mg/kg)
resulted in a rapid absorption of compound into the systemic circulation with an observed
Cmax at 1.5 h post-dose followed by a prolonged terminal phase. TBBPA concentrations in
plasma decreased rapidly after an IV dose (25 mg/kg) followed by a long elimination phase.
These results indicate low systemic bioavailability (F < 0.05), similar to previous reports
using male rats. Elimination pathways appeared to become saturated leading to delayed
excretion after a single oral administration of the highest dose (1000 mg/kg); no such saturation
or delay was detected at lower doses. Chronic high exposures to TBBPA may result
in competition for metabolism with endogenous substrates in extrahepatic tissues (e.g.,
SULT1E1 estrogen sulfation) resulting in endocrine disruption.