AEGL-3 VALUES

10 min

30 min

1 h

4 h

8 h

Not recommended

Not recommended

Not recommended

Not recommended

Not recommended

Reference: Not applicable.

Test Species/Strain/Sex/Number: Not applicable.

Exposure Route/Concentrations/Durations: Not applicable.

Effects: Not applicable.

End Point/Concentration/Rationale: For the derivation of AEGL-3 values, no relevant and well-documented LC50 studies were available.

Although oral lethality data in animals are available, they were not used as a basis for derivation of AEGL values because of the uncertainty regarding local effects of MCAA in the respiratory tract. Several mechanistic aspects point at a possible role of local effects: (1) MCAA has a pKa of 2.85 and thus is a strong acid, which may cause irritation and local tissue damage by its acidity alone; (2) MCAA can bind to sulfhydryl groups, for example, those of reduced glutathione, and may thus cause lung damage through glutathione depletion; and (3) during inhalation exposure, local concentrations of MCAA in the respiratory tract could cause local tissue damage by enzyme inhibition already in doses lower than those required for systemic effects in oral studies. Experimental findings support a possible local effect on the respiratory tract: (1) the available inhalation studies report effects on the respiratory tract, and (2) MCAA causes severe local damage to skin and eyes.

Unfortunately, in the only LC50 study located in the literature (Maksimov and Dubinina, 1974), data presentation is inadequate. Because pathologic findings were not reported, it remains unknown whether rats died from local lung tissue destruction or from systemic toxicity (that is, acidosis affecting CNS or heart).

Inhalation studies using MCAA esters were not considered relevant for the derivation of AEGL-3 values; compared with MCAA, local effects of its esters are less likely, because (1) the esters are not acidic and thus do not cause local effects by lowering the tissue pH value; and (2) local effects due to glutathione binding or enzyme inhibition can be expected to be smaller because the esters have to get hydrolyzed enzymatically to free MCAA first. Although quantitative data for the hydrolysis are lacking, it is likely that due to its rapid distribution in the body, much of the deposited ester will enter systemic circulation before it is hydrolyzed, and thus the concentration of MCAA in respiratory tract tissue is likely to be much smaller during inhalation exposure to MCAA esters than during MCAA exposure.

Due to the inadequate presentation of the only LC50 available (Maksimov and Dubinina 1974) and the uncertainties of a route-to-route extrapolation, AEGL-3 values were not recommended.

Uncertainty Factors/Rationale: Not applicable.

Modifying Factor: Not applicable.

Animal to Human Dosimetric Adjustment: Not applicable.

Time Scaling: Not applicable.

Data Adequacy: Adequate animal data relevant for the derivation of AEGL-3 values are not available.



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