LEUKEMIA INDUCED IN RATS BUT NOT MICE BY DIMETHYL MORPHOLINOPHOSPHORAMIDATE, A SIMULANT ANTICHOLINESTERASE AGENT

Dimethyl morpholinophosphoramidate (DMMPA), an organophosphate, caused leukemia in male and female Fischer 344/N rats. DMMPA was administere d in corn oil by oral intubation to groups of 50 male and 50 female ra ts at 0, 150, 300, or 600 mg/kg body weight, five times per week for 2 years. B6C3F1 mice were given 0, 150 (males only), 300, and 600 (fema les only) mg/kg body weight under the same schedule. DMMPA induced a d ose-related enhancement in the incidence of mononuclear cell leukemia in rats - males: controls = 14/50, 150 mg group 21/50; 300 mg group = 19/50; 600 mg group = 25/50; females: controls = 9/50, 150 mg group = 13/50; 300 mg group = 12/49; 600 mg group = 18/50. Survival-adjusted r ates strengthen the DMMPA effect: males - 31%, 50%, 47%, and 63%; fema les - 20%, 32%, 30%, 50%. Latent periods for mononuclear cell leukemia development in exposed rats were not shortened compared to controls. No carcinogenic effects in mice were detected. DMMPA was not mutagenic in Salmonella, was mutagenic for mouse lymphoma cells, and induced bo th chromosome aberrations and sister chromatid exchanges in Chinese ha mster ovary cells.