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 (20mg/kg) by oral gavage or IV administration. Following a single oral administration of TBBPA-DBPE, elimination of [(14)C] equivalents in the feces was extensive and rapid (95% of dose by 36h). 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 [(14)C] equivalents was much slower (27% of dose eliminated by 36h, 71% by 96h). 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(1/2beta): 24.8h; CL(b): 0.1mLmin(-1). Kinetic constants following oral dosing were: t(1/2alpha): 2.5h; t(1/2beta): 13.9h; CL(b): 4.6mLmin(-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 24h (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.
Knudsen
G A
GA
Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ, United States.
Jacobs
L M
LM
Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ, United States.
Kuester
R K
RK
Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ, United States.
Sipes
I G
IG
Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ, United States. Electronic address: sipes@email.arizona.edu.
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000737:chemistry; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D005411:Flame Retardants / Q000493:pharmacokinetics*; D022781:Hepatocytes / Q000378:metabolism; D008658:Inactivation, Metabolic; D007275:Injections, Intravenous; D008297:Male; D011075:Polybrominated Biphenyls / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D005411:Flame Retardants; D011075:Polybrominated Biphenyls; C020806:tetrabromobisphenol A