Toxicology and pathology of repeated doses of monomethylhydrazine in monkeys. AMRL-TR-66-199.

The effects of daily repeated doses of monomethylhydrazine (MMH) were studied in monkeys. Groups of monkeys were given from 2.5 to 5 mg/kg IMH i.p. for a total of 23 doses. Other monkeys were given from 7 to 10 mg/kg MMH i.p. for up to 4 days. Baseline and weekly clinical laboratory measurements studied were complete blood count, serum glucose, alkaline phosphatase, and glutamic oxaloacetic transaminase. At the end of the exposures, necropsies were performed on all animals. Special studies included fat stains of fresh cryostat sections of heart, liver, and luxol fast blue stains of pons, cerebellum, basal ganglia, and insular cortex. Results of the experiments have delineated the limits of toxicity for MMH in primates, as evaluated by clinical chemistry, symptomatology, and pathological examination. Repeated doses of 5 mg/kg caused emesis and some convulsions when a total of 15 mg/kg was reached. Animals tolerated daily doses of 2.5 mg/kg for a total of 23 injections with no significant effects. Other animals tolerated 12 doses of 5 mg/kg per day after having received 5 mg/kg each day for 3 days and 2.5 mg/kg for 8 days or 95 mg/kg for a 4-week period. This experiment tends to negate a tolerance phenomenon. The most significant conclusions from the experiments are the relative lack of pathological (either anatomical or clinical) alterations seen in the acute intoxications and the extremely narrow limits between a no-effect and lethal dose level. Of extreme interest is the absence of kidney malfunction or renal pathology in these studies as contrasted by results seen in dogs at these dose levels. MMH causes marked renal damage in dogs.