Hepatotoxicity of dimethylformamide and dimethylsulfoxide at and above the levels used in some aflatoxin studies.
Albino rats were each treated with a single intraperitoneal injection of dimethylformamide (DMF) or dimethysulfoxide (DMSO). The doses of DMF administered were 0.6, 0.9, and 1.2 ml. per kg. and those of DMSO were 1.2, 2.4, 3.6, and 4.8 ml. per kg. The animals were sacrificed at 24, 48, 72, and 120 hours following administration of each dose. The liver was investigated in all cases. Treatment with DMF at 0.6 ml. per kg. indicated some histologic lesions of the liver which became well defined at 0.9 and 1.2 ml. per kg. causing severe central phlebitis with centrilobular coagulative necrosis of the cells associated with a heavy inflammatory infiltrate. Maximal liver lesions occurred at 48 hours and started to regress after 72 hours. However, cellular atypism became a consistent finding after this inflammatory phase. DMSO-treated animals showed minimal histologic lesions of the liver at 1.2 and 2.4 ml. per kg. Higher doses caused fatty infiltration with a predominatly periportal distribution. It tended to produce its maximal effect in 12 hours which then regressed rapidly after 24 hours. The development of histologic lesions in the liver even at 0.6 ml. per kg. suggests that DMF is not a suitable solvent for aflatoxin studies, and hence the results obtained from such studies need cautious interpretation. DMSO appears to be an ideal alternative for toxicologic studies at a much higher dose level compared to DMF.