Effect of four-week repeated inhalation exposure to unconjugated azodicarbonamide on specific and non-specific airway sensitivity of the guinea pig

Reports of respiratory problems among industrial workers exposed repeatedly by inhalation to azodicarbonamide (ADA) raised concern that ADA might be a pulmonary sensitizer. We used a non‐invasive method for measuring specific airway conductance to evaluate the potential for repeated inhalation of unconjugated ADA to cause specific or non‐specific pulmonary sensitization in the guinea pig. Two groups of male Hartley guinea pigs were exposed 6 h/day, 5 days/week for 4 weeks to aerosolized ADA at 51 or 200 mg/m3, or to filtered air as controls. One group was tested for specific sensitization to ADA by measuring specific airway conductance during inhalation challenge with ADA before and on the third day after the 4‐week ADA exposure. The ADA concentrations for the challenges were identical to the repeated exposure concentrations (51 or 200 mg/m3, 200 mg/m3 for controls). The other group was tested for non‐specific airway sensitization by inhalation challenge with aerosolized histamine before and after the 4‐week ADA exposure. Histamine was administered in stepwise increasing concentrations to elicit an airway response in each guinea pig. Skin tests for immunological responses to ADA, body weight and histopathology of the respiratory tract and skin test sites were also evaluated. The 4‐week exposure to ADA did not result in either specific or non‐specific airway sensitization. The ADA exposure did not induce positive skin reactions, influence body weight or cause histopathological responses. These results indicate that ADA, acting alone (i.e. not conjugated to a protein), is not a pulmonary sensitizer in the guinea pig exposed repeatedly for 4 weeks and challenged to simulate a ‘Monday morning’ exposure.