Effect of Inhaled Azodicarbonamide on F344/N Rats and B6C3F1 Mice with 2-Week and 13-Week Inhalation Exposures

Effect of Inhaled Azodicarbonamide on F344/N Rats and B6C3F,Mice with 2-Week and 13-Week Inhalation Exposures. MEDINSKY,M. A., BECHTOLD, W. E., BIRNBAUM, L. S., BOND, J. A., BURT,D. G., CHENG, Y. S., GILLFTT, N. A., GULATI, D. K., HOBBS, C.H., AND PICK-RELL, J. A. (1990). Fundam. Appl. Toxicol 15, 308/319.Azodicarbonamide (ADA), a compound used in the baking and plasticsindustries, has been reported to cause pulmonary sensiti-zationand dermatitis in people. Two-week repeated and 13-week subchronicinhalation exposures of F344/N rats and B6C3F, mice to ADA wereconducted to determine the toxicity of inhaled ADA. The meanair concentrations of ADA in the 2-week studies were 207, 102,52, 9.4, or 2.0 mg/m3. No exposure-related mortality nor abnormalclinical signs were observed in rats or mice during or afterexposure. The terminal body weights were slightly depressedin the highest exposure group. Liver weights were lower in malerats exposed to 200 mg ADA/m3. No significant lesions were notedon either gross or histologic evaluation of rats or mice. Inthe 13-week subchronic study, the mean air concentrations ofADA were 204, 100, or 50 mg/m3. No mortality or clinical signsrelated to exposure were observed. The terminal body weightsof exposed rats were not significantly different from thoseof control rats but were significantly depressed in mice exposedto 100 or 200 mg ADA/m3. No histopathological lesions were notedin mice. Lung weights were increased and enlarged mediastinaland/or tracheobronchial lymph nodes were noted in rats exposedto 50 mg ADA/m3. No exposure-related lesions were observed microscopicallyin rats exposed to 100 or 200 mg ADA/m3. All rats in the 50mg ADA/m3 exposure group only had lung lesions that consistedof perivascular cuffing with lymphocytes and a multifocal typeII cell hyperplasia, suggesting a possible immune reaction toan antigen in the lung. Viral titers for rats exposed to 50mg ADA/m3 were negative for Sendai virus and pneumonia virusof mice, which produce similar lesions. The possibility of anunknown viral antigen causing this lesion cannot be eliminated.Lung tissue from male rats was analyzed for ADA and biurea,the major metabolite of ADA. No ADA was detected. The amountof biurea in the lungs increased nonlinearly with increasingexposure concentration, suggesting that clearance was somewhatimpaired with repeated exposures. However, even at the highestexposure concentration, this amount of biurea was less than1 % of the estimated total ADA deposited over the exposure period.In summary, ADA is rapidly cleared from the lungs, even wheninhaled at concentrations up to 200 mg/m3. Exposure to ADA forup to 13 weeks did not appear to be toxic to rodents