Metabolism and distribution of bromodichloromethane in rats after single and multiple oral doses.
The disposition of [14C]bromodichloromethane (BDCM) was studied in male Fischer rats after single oral doses of 1, 10, 32, or 100 mg/kg and 10-d repeat oral dosing of 10 or 100 mg/kg/d. Methods were developed to quantitate exhaled 14CO and 14CO2. Bromodichloromethane was extensively (approximately 80-90%) metabolized within 24 h postdosing with approximately 70-80% of the administered dose appearing as 14CO2 and approximately 3-5% as 14CO. Urinary and fecal elimination were low, accounting for 4-5% and 1-3% of the dose, respectively. Oral administration of BDCM at a level of 10 mg/kg/d for 10 d did not result in the bioaccumulation or altered disposition of the test chemical, but during the course of the repeat 100 mg/kg/d dosing the rate of production of 14CO2 increased, suggesting that this dose of BDCM induced its own metabolism. Persistence of radiolabeled residues in tissues collected 24 h after single-dose administration was low (3-4% of dose), with the most marked accumulation (1-3% of dose) in liver. Kidney tissue, particularly the cortical region, also contained significant concentrations of residues.
Mathews
J M
JM
Center for Bioorganic Chemistry, Research Triangle Institute, North Carolina 27709-2194.
Troxler
P S
PS
Jeffcoat
A R
AR
D000284:Administration, Oral; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006846:Hydrocarbons, Halogenated / Q000378:metabolism*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D022882:Trihalomethanes
D006846:Hydrocarbons, Halogenated; D022882:Trihalomethanes; D002245:Carbon Dioxide; C025191:bromodichloromethane