Effect of dose on the metabolism of 1,1,2,2-tetrabromoethane in F344/N rats after gavage administration.
1,1,2,2-Tetrabromo[U-14C]ethane ([14C]TBE) was used to study the metabolism of TBE in rats. Three graded doses of TBE (1.17, 13.6, and 123 mg/kg; 1 microCi 14C/rat at each dose) were administered by gavage to three groups of four rats each. Excreta samples were collected at various time intervals up to 96 hr. Following euthanization, 14C activity was measured in the excreta, tissues, and carcass. The fraction of the dose exhaled as volatile metabolites of TBE, excluding 14CO2, was approximately 9-10% higher in rats given the high dose of TBE compared to that in rats given either the low or the medium dose. The fraction excreted in the urine decreased with increasing TBE dosage. 1,2-Dibromoethylene and tribromoethylene were identified as exhaled metabolites at the high dose. Three major urinary metabolites were identified: dibromoacetic acid, glyoxylic acid, and oxalic acid. The results of this study indicate that the metabolism of TBE was linear up to a dose of 13.6 mg/kg, but the contribution of various TBE metabolic pathways was different at a dose of 123 mg/kg.
Kennedy
C H
CH
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185.
Cohen
K B
KB
Bechtold
W E
WE
Chang
I Y
IY
Eidson
A F
AF
Dahl
A R
AR
Henderson
R F
RF
D000085:Acetates; D000284:Administration, Oral; D000818:Animals; D062845:Chloroacetates; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D006038:Glyoxylates / Q000652:urine; D006842:Hydrocarbons, Brominated / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity / Q000652:urine; D008297:Male; D010070:Oxalates / Q000652:urine; D019815:Oxalic Acid; D051381:Rats; D011916:Rats, Inbred F344; D014238:Trichloroacetic Acid / Q000652:urine
D000085:Acetates; D062845:Chloroacetates; D006038:Glyoxylates; D006842:Hydrocarbons, Brominated; D010070:Oxalates; D014238:Trichloroacetic Acid; C017766:tribromoacetic acid; D019815:Oxalic Acid; C031150:glyoxylic acid; C037530:1,1,2,2-tetrabromoethane