sponses, and some evidence of renal and hepatic toxicity. Lethal exposures are usually preceded by convulsions. Lethal toxicity varies somewhat among species. One-hour LC50 values of 162, 82, 96, 244, 122, and 991 ppm have been determined for rhesus monkeys, squirrel monkeys, beagle dogs, rats, mice, and hamsters, respectively. Exposure concentration-exposure time relationships appear to follow a linear relationship, although there appears to be a critical threshold for lethality with little margin between exposures causing only minor reversible effects and those resulting in lethality.

In a 1-year inhalation bioassay using dogs, rats, mice, and hamsters and monomethylhydrazine concentrations of 2 ppm and 5 ppm, there was no evidence of treatment-related carcinogenicity in dogs or rats even after a 1-year postexposure observation period. However, mice exposed to 2 ppm exhibited an increased incidence of lung tumors, nasal adenomas, nasal polyps, nasal osteomas, hemangioma, and liver adenomas and carcinomas. In hamsters exposed to 2 or 5 ppm, there was an increase in nasal polyps and nasal adenomas (5 ppm only), interstitial fibrosis of the kidney, and benign adrenal adenomas. Recommendation of AEGL-1 values for monomethylhydrazine would be inappropriate. This conclusion was based on the fact that notable toxicity may occur at or below the odor threshold. Exposure concentration-exposure duration relationships for monomethylhydrazine indicated little margin between exposures that produce no adverse health effect and those that result in significant toxicity.

The AEGL-2 values were derived by a 3-fold reduction of the AEGL-3 values. This approach for estimating a threshold for irreversible effects was used in the absence of exposure-response data related to irreversible or other serious long-lasting effects. It is believed that a 3-fold reduction in the estimated threshold for lethality is adequate to reach the AEGL-2 threshold level because of the steep dose-response relationship.

For AEGL-3, lethality data (1-h LC50 of 82 ppm) for squirrel monkeys (Haun et al. 1970) were downwardly adjusted by a factor of 3 to estimate a lethality threshold (27.3 ppm). Temporal scaling to obtain time-specific AEGL values was described by C1 × t = k (where C = exposure concentration, t = exposure duration, and k = a constant). The lethality data for the species tested indicated a near-linear relationship between concentration and time (n = 0.97 and 0.99 for monkeys and dogs, respectively). The derived exposure values were adjusted by a total uncertainty factor of 10. An uncertainty factor of 3 was applied for interspecies variability with the following justification. One-hour LC50s were determined for the monkey, dog, rat, and mouse. The LC50 values ranged from 82 ppm in the squirrel monkey to 244 ppm in the mouse, differing by a factor of approximately 3. The squirrel monkey data (1-h LC50 = 82 ppm) were used to determine the AEGL-3 because this species appeared to be the most sensitive to monomethylhydrazine toxicity and because it was the species most closely related to humans. An uncertainty factor of 3 for protection of sensitive individuals was applied to reflect individual variability of less than an order of magnitude. Although the mechanism of toxicity is uncertain and sensitivity among individuals may vary, the exposure-response relationship for each spe-



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