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 CO 2.