title: Review of investigations of dichloromethane metabolism and subchronic oral toxicity as the basis for the design of chronic oral studies in rats and mice.
abstract: In preparation for the design and performance of chronic toxicity and carcinogenicity studies in rats and mice on dichloromethane (methylene chloride; DCM), biochemical, mutagenicity, short-term, metabolic and subchronic feeding studies were carried out. These studies established that it was feasible to present DCM to rodents at adequate levels in drinking-water. Saturation of metabolic pathways was demonstrated in both rats and mice at oral doses of approximately 100 mg/kg. The lowest toxic effect levels after 90 days of treatment were found to be approximately 190 and 580 mg/kg for rats and mice, respectively. Dose, vehicle and the exposure regimen were found to affect DCM challenge to target tissues and its metabolism to CO and CO2.
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D001345:Autoradiography; D001944:Breath Tests; D002248:Carbon Monoxide / Q000032:analysis; D002250:Carbon Radioisotopes; D005260:Female; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism*; D007700:Kinetics; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D008452:Maximum Allowable Concentration; D008752:Methylene Chloride / Q000378:metabolism* / Q000633:toxicity / Q000652:urine; D051379:Mice; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D006843:Hydrocarbons, Chlorinated; D008752:Methylene Chloride; D002248:Carbon Monoxide