The pharmacokinetics of dichloromethane. II. Disposition in Fischer 344 rats following intravenous and oral administration.
The tissue distribution and metabolism of dichloromethane (DCM; CH2Cl2) was investigated in Fischer 344 rats following iv or oral administration. The route and level of exposure were found to have a significant effect on the disposition characteristics. A two-compartment model was used to describe the elimination of DCM from blood following single iv doses. The estimates of t1/2,beta were 11.9 and 23.5 min for doses of 10 and 50 mg/kg, respectively, and the disposition rate constants, beta were found to differ significantly at P less than 0.05. When DCM was administered orally (by gavage) in a daily dose of 50 or 200 mg/kg for 14 consecutive days, rapid absorption and distribution to the tissues characterized the disposition. Dose-dependent metabolism to 14CO2 and 14CO and rapid pulmonary clearance of unchanged 14CH2Cl2 were the dominant routes of elimination of DCM from the body following both iv and oral doses. No observable pharmacokinetic or metabolic effect resulted from repeated oral dosing.
D000284:Administration, Oral; D000818:Animals; D001944:Breath Tests; D002245:Carbon Dioxide / Q000032:analysis; D002248:Carbon Monoxide / Q000032:analysis; D002250:Carbon Radioisotopes; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism*; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007700:Kinetics; D008168:Lung / Q000378:metabolism; D008297:Male; D008752:Methylene Chloride / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D006843:Hydrocarbons, Chlorinated; D002245:Carbon Dioxide; D008752:Methylene Chloride; D002248:Carbon Monoxide