Reference: Not applicable

Test Species/Strain/Number: Not applicable

Exposure Route/Concentrations/Durations: Not applicable

Effects: Not applicable

Endpoint/Concentration/Rationale: Not applicable

Uncertainty Factors/Rationale: Not applicable

Modifying Factor: Not applicable

Animal to Human Dosimetric Adjustment: Not applicable

Time Scaling: Not applicable

Data Adequacy: Numeric values for AEGL-1 are not recommended because (1) data are not available, (2) data indicate that toxic effects may occur at or below the odor threshold, (3) an inadequate margin of safety exists between the derived AEGL-1 and the AEGL-2, or (4) the derived AEGL-1 is greater than the AEGL-2. Absence of an AEGL-1 does not imply that exposure below the AEGL-2 is safe.

Reference: Weeks, M.H., G.C.Maxey, M.E.Sicks, and E.A.Greene. 1963. Vapor toxicity on UDMH in rats and dogs from short exposures. Am. Ind. Hyg. Assoc. J. 24:137–143

Test Species/Strain/Sex/Number: mongrel dogs, 2–4/group, sex not specified

Exposure Route/Concentrations/Durations: Inhalation; 1,200–4,230 ppm for 5 min; 360, 400, or 1,530 ppm for 15 min; 80–250 ppm for 60 min

Effects:

Exposure (15 min)

Effect

360 ppm

muscle fasciculations in 1 of 4 dogs (determinant for AEGL-2)

400 ppm

behavioral changes in 2 of 4 dogs

1,530 ppm

tremors, convulsions, vomiting in 2 of 2 dogs

Endpoint/Concentration/Rationale: 15-min exposure at 360 ppm considered a threshold for potentially irreversible effects or effects that would impair escape. At this exposure, muscle fasciculations were observed in 1 of 4 exposed dogs, and at 400 ppm, behavioral changes were observed.

Uncertainty Factors/Rationale: Total uncertainty factor: 30

Interspecies: 3—The toxic response to dimethylhydrazine (LC₅₀ values) was similar across species. The 4-h LC₅₀ values for mouse, rat, and hamster differ by a factor of approximately 2 and were consistent with the dog data when extrapolated from 1 h using n=1. The more susceptible species, the dog, was used to derive the AEGL-2 values.

Intraspecies: 10—A broad spectrum of effects were seen, including behavioral effects, hyperactivity, fasciculations, tremors, convulsions, and vomiting. The mechanism of toxicity is uncertain and susceptibility among individuals regarding these effects may vary. This variability was especially demonstrated in dogs wherein responses varied from one of extreme severity (vomiting, tremors, convulsions, and death) to no observable effects. Therefore, a factor of 10 was applied. A factor of 10 was also applied because experiments by Weeks et al. (1963) indicated that dogs had been previously stressed (auditory stimuli), which may have affected their response to dimethylhydrazine. Based upon these data, it was assumed that humans may be equally variable in their response to dimethylhydrazine.

Modifying Factor: None

Animal to Human Dosimetric Adjustment: None applied, insufficient data

Time Scaling: Cⁿ×t=k, where n=1 and k=180 ppm·min; LC₅₀ data were available for 5-, 15-, 30-, 60-, and 240-min exposures in rats and 5-, 15-, and 60-min in dogs. Exposure-response data indicated a near linear concentration-response relationship (n=0.84 for rats; n=0.80 for dogs). For time-scaling, a linear relationship was assumed and a value where n=1 was selected.

Data Adequacy: Information regarding the human experience for acute inhalation exposure to dimethylhydrazine are limited to qualitatively case reports indicating nasal and respiratory tract irritation, breathing difficulties, and nausea. Data in animals have shown concentration-dependent effects ranging from respiratory tract irritation, pulmonary edema and neurologic effects to lethality. Because the nonlethal effects in humans and animals are qualitatively similar, the animal data were considered relevant and appropriate for development of AEGL values. The AEGL values for dimethylhydrazine reflect the steep exposure-response relationship suggested by available data.

Reference: Weeks, M.H., G.C.Maxey, M.E.Sicks, and E.A.Greene. 1963. Vapor toxicity of UDMH in rats and dogs from short exposures. Am. Ind. Hyg. Assoc. J. 24:137–143

Test Species/Strain/Sex/Number: mongrel dogs, 3–4/group; sex not specified

Exposure Route/Concentrations/Durations: Inhalation; exposure to various concentrations (80–22,300 ppm) for 5, 15, or 60 min

Effects:

1-h LC₅₀

981 ppm (reduction by 1/3 was basis for AEGL-3 derivation)

15-min LC₅₀

3,580 ppm

5-min LC₅₀

22,300 ppm

Endpoint/Concentration/Rationale: 1-h LC₅₀ (981 ppm) reduced by 1/3 was considered an estimate of the lethality threshold (327 ppm). Based on the available exposure-response data for this chemical (Jacobson et al. 1955), a 3-fold reduction in LC₅₀ values results in exposures that would not be associated with lethality.

Uncertainty Factors/Rationale: Total uncertainty factor: 30

Interspecies: 3—The toxic response to dimethylhydrazine (LC₅₀ values) was similar across species. The 4-h LC₅₀ values for mouse, rat, and hamster differ by a factor of approximately 2 and were consistent with the dog data when extrapolated from 1 h using n=1. The more susceptible species, the dog, was used to derive the AEGL-3 values.

Intraspecies: 10—A broad spectrum of effects were seen, including behavioral effects, hyperactivity, fasciculations, tremors, convulsions, and vomiting. The mechanism of toxicity is uncertain, and susceptibility among individuals regarding these effects may vary. This variability was especially demonstrated in dogs wherein responses varied from one of extreme severity (vomiting, tremors, convulsions, and death) to no observable effects. Therefore, a factor of 10 was used. A factor of 10-fold was also used because experiments by Weeks et al. (1963) indicated that dogs previously stressed by auditory stimuli may have a potentiated response to dimethylhydrazine. Based upon these data, it was assumed that humans may be equally variable in their response to dimethylhydrazine subsequent to similar stresses.

Modifying Factor: None

Animal to Human Dosimetric Adjustment: None applied, insufficient data

Time Scaling: Cⁿ×t=k, where n=1 and k=654 ppm·min; LC₅₀ data were available for 5-, 15-, 30-, 60-, and 240-min exposures in rats and 5-, 15-, and 60-min in dogs. Exposure-response data indicated a near linear concentration-response relationship (n=0.84 for rats; n=0.80 for dogs). For time-scaling, a linear relationship was assumed and a value where n=1 was selected by the National Advisory Committee.

Data Adequacy: Information regarding the lethality of dimethylhydrazine in humans were not available. Lethality data for several animal species allowed for a defensible development of the AEGL-3 values but uncertainties remain regarding individual variability in the toxic response to dimethylhydrazines.