Histopathological investigation of DMF-induced hepatotoxicity.

N,N-Dimethylformamide (DMF) has been implicated in the production of hepatotoxicity in male and female F344 rats. Repeated administration of dosages of 0.75 and 1.0 ml/kg DMF for up to 12 weeks produced massive liver necrosis associated with decreased body weight gain. Macroscopically, areas of necrotic change were well pronounced in every hepatic lobe, being yellowish-red in coloration, irregular in shape, and varying in size, but were most striking immediately adjacent to the porta hepatis. Among the lobes, those which were relatively small were most markedly affected, and occasionally an entire lobe was involved. Light and electron microscopic studies revealed the hepatic architecture to be occupied by massive fibrosis. There were, however, sharp lines of demarcation between surviving normal and necrotic areas. Hemosiderosis involving macrophages was accompanied by proliferative bile ductules and a number of multinucleated giant cells. The distribution and quality of the hepatic lesions produced by DMF were discussed.