title: A two-year drinking-water study of dichloromethane in rodents. I. Rats.
abstract: In order to evaluate its toxicity and carcinogenic potential, dichloromethane (DCM) at levels of 0, 0, 5, 50, 125 and 250 mg/kg body weight/day was administered in deionized water to a total of 500 Fischer 344 rats of each sex for 104 wk. An additional group received a level of 250 mg/kg body weight/day for 78 wk followed by a 26-wk recovery period during which only deionized water was presented. Kills were performed at 26-wk intervals. Statistically significant effects on body weight, water consumption and food consumption were observed at the two highest dose levels. Minimal effects were noted on the haematological and serum chemistry parameters monitored. Treatment-related hepatic changes were observed histomorphologically in both sexes after 78 wk of treatment. These changes consisted of an increased incidence of foci/areas of cellular alteration and of fatty change at all dose levels except the lowest. A decrease in the severity of fatty change was observed in the recovery group, but no difference was noted in the incidence of cellular alteration. An increased incidence of hepatic tumours noted in females treated at 50 and 250 mg/kg/day was within the range of historical control incidences. In view of an unusually low incidence of similar tumours in the concurrent control groups and the absence of an increased incidence of hepatic tumours in the group treated at 125 mg/kg/day, the effect seen at 50 and 250 mg/kg/day was not considered to be attributable to DCM treatment. Under the experimental conditions of this study, there was a no-observable-effect level of 5 mg/kg/day in both males and females.
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001769:Blood / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D005260:Female; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008752:Methylene Chloride / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D006843:Hydrocarbons, Chlorinated; D008752:Methylene Chloride