Absorption, distribution, metabolism and excretion of intravenously and orally administered tetrabromobisphenol A [2,3-dibromopropyl ether] in male Fischer-344 rats

Tetrabromobisphenol A bis[2,3-dibromopropyl ether],2,2-bis [3,5-dibromo-4- (2,3-dibromopropoxy)phenyl] propane is a brominated flame retardant with substantial U.S. production. Due to the likelihood of human exposure to TBBPA-DBPE and its probable metabolites, studies regarding the absorption, distribution, metabolism, and excretion were conducted. Male Fischer-344 rats were dosed with TBBPA-DBPE (20 mg/kg) by oral gavage or IV administration. Following a single oral administration of TBBPA-DBPE, elimination of [C-14] equivalents in the feces was extensive and rapid (95% of dose by 36 h). Following repeated daily oral doses for 5 or 10 days, route and rate of elimination was similar to single administrations of TBBPA-DBPE. After IV administration, fecal excretion of [C-14] equivalents was much slower (27% of dose eliminated by 36 h, 7 1 % by 96 h). Urinary elimination was minimal (< 0.1 %) following oral or IV administration. A single peak that co-eluted with the standard of TBBPA-DBPE was detected in extracts of whole blood following oral or IV administration. TBBPA-DBPE elimination from the blood was slow. Kinetic constants following IV dosing were-t(1/2 beta): 24.8 h; CLb: 0.1 mL min(-1). Kinetic constants following oral dosing were: t(1/2 alpha): 2.5 h; t(1/2 beta): 13.9 h; CLb: 4.6 mL min(-1). Systemic bioavailability was 2.2%. Liver was the major site of disposition following oral or IV administration. After oral administration, 1 % of the dose was eliminated in bile in 24 h (as metabolites). In in vitro experiments utilizing hepatocytes or liver microsomal protein, no detectable metabolism of TBBPA-DBPE occurred. These data indicate that TBBPA-DBPE is poorly absorbed from the gastrointestinal tract. Compound which is absorbed is sequestered in the liver, slowly metabolized, and eliminated in the feces. (c) 2007 Published by Elsevier Ireland Ltd.