Studies on the toxicity of the antitumour agent N-methylformamide in mice

Aspects of the toxicology of N-methylformamide (NMF), an investigational antitumour agent, were studied in mice. After injection of NMF at its LD10 (800 mg/kg) dosage the total peripheral white blood cell and platelet counts were unchanged in BALB/c mice. A mild granulocytosis was seen in this strain after administration of the LD50 (2300 mg/kg) dosage. Plasma activity of the enzyme sorbitol dehydrogenase in BDF1 mice was markedly increased after either a single injection of not less than 800 mg/kg or a chronic treatment of not less than 400 mg/kg/day over 5 days indicating the drug to be hepatotoxic. Plasma activities of L-alanine and L-aspartate aminotransferases were also increased after the chronic treatment. Chronic administration of NMF was less hepatotoxic than single dose administration of the same total dose and also increased the antitumour efficacy of NMF against the M5076 sarcoma. These results indicate that the maximum therapeutic benefit of NMF might be obtained by the use of chronic schedules and that the drug is not myelosuppressive.