Biochemical Response to 1,1-dimethylhydrazine (udmh).

Owing to their present use as rocket fuels and their pharmacologic activity as central nervous system stimulants, substituted hydrazines and hydrazine derivatives have come into increasing use in recent years. The parent compound hydrazine and the methyl-substituted hydrazines are of potential hazard because of their toxicity, volatility, and explosive nature. Exposure to hydrazine vapor brings about central nervous system (CNS) effects resulting in clonic-tonic convulsions and death if the exposure is severe; in addition, hydrazine at lower levels of exposure will severely damage the liver, resulting in necrosis and fatty infiltration (Comstock et al., 1954). Inhalation of l,l-dimethylhydrazine (unsymmetrical dimethylhydrazine, UDMH), while producing similar CNS effects, is apparently lacking the severe hepatotoxic effects of hydrazine (Rinehart et al., 1960). The differences in hepatotoxic action and the exact mechanisms by which these compounds exert their CNS effects are not clear, although several recent reports have demonstrated that UDMH inhibits glutamic acid decarboxylase and y-aminobutyrica-ketoglutaric transaminase activities in brain tissue. This inhibition can be reversed and CNS symptoms alleviated by pyridoxine hydrochloride (Medina et al., 1962; Reeves, 1961). The present study was undertaken with two objectives in mind: to study the cytotoxic effect of UDMH on tissues and to evaluate several techniques that might be of value as sensitive indexes of tissue damage due to UDMH exposure. Serum glutamicoxalacetic transaminase (GOT) was determined since it has been shown to be a relatively sensitive index of liver damage. Urinary amino acid excretion was measured since it may reflect liver or kidney damage or altered protein and amino acid metabolism. Brain and liver sulfhydryl levels were also studied, as they may be affected by the chemical reactivity of UDMH or by its effect on the oxidation-reduction state of the tissue. Histopathologic examination of the various tissues was also included in this study.