Metabolism and disposition of 2,2',4,4'- tetrabromodiphenyl ether following administration of single or multiple doses to rats and mice.
The metabolism and disposition of (14)C-labelled 2,2',4,4'-tetrabromodiphenyl ether (BDE47) were investigated in F344 rats and B6C3F1 mice. Approximately 75-85% of 1 micromol BDE47 kg(-1) was absorbed following oral administration to either rats or mice. Sex and species differences were observed in tissue distribution and excretion of BDE47-derived radioactivity. Absorption and distribution of (14)C to major tissues were dose-proportional in male rats from 0.1 to 1,000 micromol kg(-1). BDE47-derived radioactivity increased in all rat and mouse tissues examined following repeated daily doses of 1 micromol kg(-1). Accumulation of (14)C in tissues of mice was less than in corresponding rat tissues. Glutathione conjugates of BDE47 were excreted in rat bile. A glucuronide and a sulfate conjugate of 2,4-dibromophenol were detected in the urine of BDE47-treated rats. BDE47 appears to induce its own metabolism. Increased formation of reactive metabolites over time may correlate with toxicological effects in BDE47-treated rodents.
Sanders
J M
JM
Laboratory of Pharmacology and Chemistry, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. sander10@niehs.nih.gov
Chen
L-J
LJ
Lebetkin
E H
EH
Burka
L T
LT
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D009928:Organ Specificity; D010647:Phenyl Ethers / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011075:Polybrominated Biphenyls; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D014018:Tissue Distribution
D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated; D010647:Phenyl Ethers; D011075:Polybrominated Biphenyls; C511295:2,2',4,4'-tetrabromodiphenyl ether