Fisher F344 rats and B6C3F1 mice were exposed to concentrations of 0, 150, 300, 600 and 1200 ppm of dimethylformamide (DMF) for 6 hours a day, 5 days a week for 12 weeks. Detailed clinical observations were obtained weekly and body weights biweekly on all animals. Clinical chemistry and hematology evaluations were made on all rats and approximately half the mice at terminal sacrifice. Gross necropsy examinations were made on all animals. Histopathologic evaluations were conducted on selected tissues of animals of both species at all dose levels. Few overt signs of toxicity were seen in either rats or mice. There was a dose related depression in body weight gain in rats that was significant at the 1200 ppm level from the second week of study onwards. A total of 11 mice died or were sacrificed moribund during the study, 8 from the high dose and 2 from the 600 ppm dose level. Both clinical chemistry (in rats only) and gross necropsy observations, and histopathology of tissues indicate the possibility that liver may be the target in specific organ toxicity. The no-effect DMF dose was below the 150 ppm level for both rats and mice and the maximum tolerated dose was below the 600 ppm level.

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One death (Veley, 1909) and seven cases of narcosis (Colman, 1907; Sandilands, 1909 ; M0ller, 1933) and raised serum alanine aminotransferase at 216 units. The serum bilirubin rose to 5 mg./100 ml. 48 hours after admission, subsequently falling gradually to normal. The serum alanine aminotransferase rose to over 500 units, the serum aspartate aminotransferase to 210 units, and the zinc turbidity to 10 units after nine days, thereafter slowly falling towards normal. The plasma alkaline phosphatase remained normal throughout.In the first 24 hours after admission 600 ml. of urine was passed, but the urinary output increased thereafter to a diuresis of over 5 litres on the tenth day, with a gradual lessening of albuminuria and haematuria. The blood urea rose to 205 mg./100 ml. on the fifth day, returning gradually to normal 22 days after admission. Associated with this was a rise in plasma creatinine to 10 mg./ 100 ml. The serum calcium was low on one occasion at 8.5 mg./ 100 ml., but several other recordings were normal.Her fluid intake was strictly controlled until the diuresis was established, and once oral feeding was started on the third day a high carbohydrate and restricted protein diet was given. She was discharged 23 days after admission with no symptoms. The blood urea, plasma creatinine, and urine concentration test were normal, no albuminuria or haematuria was present, and the only abnormality of liver function was a slight rise in serum alanine aminotransferase (65 units). This had returned to normal two weeks later, and three months after discharge she remained symptom-free with normal urine, blood urea, and liver function tests.