| Abstract: | The tissue distribution and metabolism of dichloromethane (DCM; CH2Cl2) was investigated in B6C3F1 mice following iv or oral administration. The route of exposure and the composition of the dosing solution were found to have a significant effect on the pharmacokinetics. Following single iv doses of 10 or 50 mg [14C]DCM/kg dose-dependent metabolism to 14CO2 and 14CO and rapid pulmonary clearance of unchanged 14CH2Cl2 characterized the elimination of DCM from the body. The highest concentrations of 14CH2Cl2 were found in the liver, lung and kidney, with more than 50% of the total radioactivity in these tissues represented by the parent compound. When DCM was administered orally in single gavage doses for 14 consecutive days at treatment levels of 50 mg/kg in water or 500 and 1000 mg/kg in corn oil, rapid absorption and elimination of DCM characterized the treatment in water while distinctly slower trends were found for the doses in corn oil. No observable pharmacokinetic or metabolic effect resulted from repeated oral dosing over the 2-wk treatment period. |
