title: Effect of inhaled azodicarbonamide on F344/N rats and B6C3F1 mice with 2-week and 13-week inhalation exposures.
abstract: Azodicarbonamide (ADA), a compound used in the baking and plastics industries, has been reported to cause pulmonary sensitization and dermatitis in people. Two-week repeated and 13-week subchronic inhalation exposures of F344/N rats and B6C3F1 mice to 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 nor 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 13-week subchronic 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. Viral titers for rats exposed to 50 mg ADA/m3 were negative for Sendai virus and pneumonia virus of mice, which produce similar lesions. The possibility of an unknown 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 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 be toxic to rodents.
authors.affiliation: Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709.
authors.forename: M A
authors.initials: MA
authors.lastname: Medinsky
authors.forename: W E
authors.initials: WE
authors.lastname: Bechtold
authors.forename: L S
authors.initials: LS
authors.lastname: Birnbaum
authors.forename: J A
authors.initials: JA
authors.lastname: Bond
authors.forename: D G
authors.initials: DG
authors.lastname: Burt
authors.forename: Y S
authors.initials: YS
authors.lastname: Cheng
authors.forename: N A
authors.initials: NA
authors.lastname: Gillett
authors.forename: D K
authors.initials: DK
authors.lastname: Gulati
authors.forename: C H
authors.initials: CH
authors.lastname: Hobbs
authors.forename: J A
authors.initials: JA
authors.lastname: Pickrell
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001391:Azo Compounds / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004798:Enzymes / Q000652:urine; D005260:Female; D008168:Lung / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D010316:Particle Size; D051381:Rats; D011916:Rats, Inbred F344; D013094:Spermatozoa / Q000187:drug effects / Q000648:ultrastructure; D014508:Urea / Q000652:urine; D014621:Vagina / Q000166:cytology / Q000187:drug effects
chemical_list: D001391:Azo Compounds; D004798:Enzymes; C004525:azodicarbonamide; D014508:Urea