Acute and subchronic toxicity of dimethylformamide and dimethylacetamide following various routes of administration

Abstract

Dimethylformamide (DMF, CAS No. 68-12-2) and dimethylacetamide (DMAC, CAS No. 127-19-5) are widely used for their superior solvent properties. A series of single and multiple dose experiments in rodents were conducted to determine the target organs, and to establish doses which, under various routes of administration, produced those changes. DMF produced moderate irritation in the rabbit eye, with the corneal response clearing in 2 to 4 weeks. DMAC produced only mild, quickly reversible conjunctival irritation. Oral doses of DMF to the rat of 2,250 mg/kg or greater produced lethality which was associated with liver damage. Lethality occurred following oral doses of 4,500 mg/kg DMAC with LD50's for male and female rats of 5,809 and 4,930 mg/kg, respectively. The 1 hour LC50 by inhalation for DMAC in the rat was 2,475 ppm or greater. Sensory irritation was produced in the mouse at concentrations of 1,658 ppm or greater for DMF. Repeated oral doses of 450 mg DMF/kg to rats produced reduced body weight gain and liver injury with both changes being reversible. DMAC tested similarly produced body weight effects, liver injury, and testicular changes in the rat with all changes again being readily reversible. Dermal doses of 2,000 mg/kg of either DMF or DMAC were poorly tolerated by rabbits. DMAC was slightly more toxic with all treated rabbits dying of acute hepatic necrosis. Repeated inhalation of 2,000-2,500 ppm produced mortality in rats exposed to DMF but not DMAC. Liver injury was seen with DMF, testicular changes with DMAC. DMF and DMAC both produced slight anemia and leukocytosis in rats during 90 days of feeding. Liver weights were elevated in rats fed DMF, but not DMAC, at a level of 1,000 ppm. The "no-observed effect level" in rats fed DMF for 90 days was 200 ppm. The overall toxicologic profiles of both DMAC and DMF are similar with the target organ being the liver.