10 min

30 min

1 h

4 h

8 h

3.3 ppm

3.3 ppm

3.3 ppm

1.8 ppm

1.2 ppm

Time Scaling: None, because the degree of irritation is expected to remain within the scope of AEGL-2 for 60 min.

Time Scaling: Cn × t = k, where n = 1.7 [n is based on regression analysis of Guzman et al. (1961) cardiotoxicity data].

Data Adequacy: Dataset was limited but adequate. All derived AEGL-2 values were well below 14 ppm, which was “intolerable” to human volunteers (Hine et al. 1960).

AEGL-3 VALUES

10 min

30 min

1 h

4 h

8 h

 

150 ppm

40 ppm

18 ppm

3.5 ppm

2.3 ppm

 

Reference: Hine, C.H., J.K. Kodama, R.J. Guzman, and G.S. Loquvam. 1960. The toxicity of allylamines. Arch. Environ. Health 1:343-352.

Test Species/Strain/Sex/Number: Long-Evans rats, five/dose group.

Exposure Route/Concentrations/Durations: Inhalation for 1, 4, or 8 h; see below:

Effects: All treated rats showed signs of eye and respiratory tract irritation, and some had lacrimation and red nasal discharge. Rats that died had stomachs distended with air, fluid-filled lungs, alveolar hemorrhage, and pulmonary edema. Mortality rates and calculated LC50 and LC01 values are as follows:

1-h exposure

4-h exposure

8-h exposure

Concentration

Mortality

Concentration

Mortality

Concentration

Mortality

1,000 ppm

1/5

133 ppm

0/5

89 ppm

0/5

1,500 ppm

1/5

200 ppm

0/5

133 ppm

0/5

2,250 ppm

3/5

300 ppm

3/5

200 ppm

4/5

3,380 ppm

5/5

450 ppm

5/5

300 ppm

5/5

LC50 = 1933 ppm

LC50 = 286 ppm

LC50 =177 ppm

LC01 = 533 ppm

LC01 = 104 ppm

LC01 = 69.2 ppm

End point/Concentration/Rationale: LC01 values, representing the lethality NOEL, were calculated by probit analysis using 1-, 4-, and 8-h exposure data from the key study.

Uncertainty Factors/Rationale:

Total uncertainty factor: 30.

Uncertainty factors: Total uncertainty factor: 30.

Interspecies: 10; to account for the lack of acute toxicity studies with AEGL-3 end points from other species.

Intraspecies: 3; steep dose-response (~2-fold increase in concentration caused mortality to increase from 0 to 100%) indicates the NOEL for lethality due to direct destruction of lung tissue is not likely to vary greatly among humans.

Modifying Factor: Not applicable.

Animal to Human Dosimetric Adjustment: Not applied.

Time Scaling: Cn × t = k, where n = 0.85, based on regression analysis of key study.

Time scaling was used only for derivation of the 10- and 30-min values, using the 1-h LC01.

Data Adequacy: The dataset was limited but adequate. The key rat study was well conducted, and the data were internally consistent.



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