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Administrative data

Description of key information

One valid sub-chronic inhalation study on rats and mice is available (Medinsky, 1990). No effect has been observed and no target organ has been identified in both species after 13-week inhalation at the highest levels tested (200mg/m3). Therefore, the NOAEL in rats and mice after sub-chronic (13 weeks) inhalation is 200mg/m3. One dietary study on ADCA and on its main metabolite (biurea) is also available (Oser, 1965) and supports this result.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
450 mg/kg bw/day
Study duration:
chronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
200 mg/m³
Study duration:
subchronic
Species:
rat

Additional information

In the Medinsky study (1990), 2 -week and 13-week repeated sub-chronic inhalation exposures of F344/N rats and B6C3F1 mice to Azodicarbonamide (ADA) were conducted to determine the toxicity of inhaled ADA. The mean air concentrations of ADA in the 2-week studies were 207, 102, 52, 9.4, or 2.0 mg/m3. No exposure-related mortality or abnormal clinical signs were observed in rats or mice during or after exposure. The terminal body weights were slightly depressed in the highest exposure group. Liver weights were lower in male rats exposed to 200 mg ADA/m3. No significant lesions were noted on either gross or histologic evaluation of rats or mice. In the 13week sub-chronic study, the mean air concentrations of ADA were 204, 100, or 50 mg/m3. No mortality or clinical signs related to exposure were observed. The terminal body weights of exposed rats were not significantly different from those of control rats but were significantly depressed in mice exposed to 100 or 200 mg ADA/m3. No histopathological lesions were noted in mice. Lung weights were increased and enlarged mediastinal and/or tracheobronchial lymph nodes were noted in rats exposed to 50 mg ADA/m3. No exposure-related lesions were observed microscopically in rats exposed to 100 or 200 mg ADA/m3. All rats in the 50 mg ADA/m3 exposure group only had lung lesions that consisted of perivascular cuffing with lymphocytes and a multifocal type II cell hyperplasia, suggesting a possible immune reaction to an antigen in the lung. Lung tissue from male rats was analyzed for ADA and biurea, the major metabolite of ADA. No ADA was detected. The amount of biurea in the lungs increased nonlinearly with increasing exposure concentration, suggesting that clearance was somewhat impaired with repeated exposures. However, even at the highest exposure concentration, this amount of biurea was less than 1% of the estimated total ADA deposited over the exposure period. In summary, ADA is rapidly cleared from the lungs, even when inhaled at concentrations up to 200 mg/m3. Exposure to ADA for up to 13 weeks did not appear to betoxic to rodents.

These results are supported by those of Oser studies on ADCA and metabolites (1965).

Justification for classification or non-classification

No target organ identified and signs of toxicity after 13 -week exposure at 200mg/m3 in rats and mice. No classification is required.