Trimellitic anhydride (TMA) is a cause of
asthma in man. Dose-dependent TMA-specific
IgE, histopathology, and airway responses after sensitization by inhalation were examined in the Brown Norway rat. Rats were exposed to 0.04, 0.4, 4, or 40 mg/m3 TMA
aerosol for 10 min, once a week, over 10 weeks. All lower exposures were, subsequently, rechallenged to 40 mg/m3 TMA
aerosol. All rats received a
sham exposure 1 week prior to the first TMA exposure. Following the
sham exposure and weekly after each TMA exposure, TMA-specific
IgE and both early-phase airway response (EAR) and late-phase airway response (LAR) were measured using enhanced pause (Penh). All rats sensitized by 40 mg/m3 TMA developed specific
IgE, EAR, and LAR to one or more of the challenges to 40 mg/m3 TMA. TMA of 4 mg/m3 induced a much lower, but stable, specific
IgE response. EAR and LAR were observed only after a 40 mg/m3 TMA rechallenge in this group, but it was much larger than that observed in the 40 mg/m3 TMA-sensitized and challenged group. Exposure-dependent histopathological changes noted included eosinophilic granulomatous
interstitial pneumonia, perivascular eosinophil infiltrates, bronchial-associated lymphoid tissue
hyperplasia, and peribronchiolar plasma cell infiltrates.