Data on acute exposures of humans to both isomers of dimethylhydrazine are limited to case reports of accidental exposures. Signs and symptoms of exposure include respiratory irritation, pulmonary edema, nausea, vomiting, and neurological effects. However, definitive exposure data (concentration and duration) were unavailable for these exposures. The limited data for humans suggest that the nonlethal toxic response to acute inhalation of dimethylhydrazine is qualitatively similar to that observed in animals (no information was available regarding lethal responses in humans). In the absence of quantitative data for humans, the use of animal data is considered a credible approach for developing AEGL values.
Toxicity data of varying degrees of completeness are available for several laboratory species, including rhesus monkeys, dogs, rats, mice, and hamsters (Weeks et al. 1963). Most of the animal studies were conducted using 1,1-dimethylhydrazine, although limited data suggest that 1,2-dimethylhydrazine exerts similar toxic effects. Minor nonlethal effects such as respiratory tract irritation appear to occur at cumulative exposures of less than 100 ppm multiplied by hours. At cumulative exposures at or only slightly greater than 100 ppm-h, more notable effects have been reported, including muscle fasciculation, behavioral changes, tremors, and convulsions. At only slightly higher exposures, lethality has been demonstrated. The available data suggest that there is very little margin between exposures resulting in no significant toxicity and those causing substantial lethality (the lethal concentration for 50% of the animals was ≈900-2,000 ppm-h).
Developmental toxicity of dimethylhydrazines has been demonstrated in rats following parenteral administration of maternally toxic doses.
Both isomers of dimethylhydrazine have been shown to be carcinogenic in rodents following oral exposure, and 6-month inhalation to 1,1-dimethylhydrazine resulted in an increased tumor response in mice, although these findings are compromised by the contaminant dimethylnitrosamine. U.S. Environmental Protection Agency (EPA) inhalation slope factors are currently unavailable for dimethylhydrazine.
AEGL-1 values for dimethylhydrazine are not recommended because of inadequate data to develop health-based criteria and because the concentration-response relationship for dimethylhydrazine indicated that a very narrow margin exists between exposures that produce no toxic response and those that result in significant toxicity.
Behavioral changes and muscle fasciculations in dogs exposed for 15 min to 360 ppm of 1,1-dimethylhydrazine (Weeks et al. 1963) served as the basis for deriving AEGL-2 values. Available lethality data in dogs and rats indicated a near-linear temporal relationship (n = 0.84 and 0.80 for dogs and rats, respectively). For temporal scaling (C1 × t = k) to derive values for AEGL-specific exposure durations, a linear concentration-response relationship, n = 1, was used. (C = exposure concentration, t = exposure duration, and k = a constant). An uncertainty factor of 3 for interspecies variability was applied because the