The pathologic and immunologic response to inhaled trimellitic anhydride in rats

Trimellitic anhydride (TMA) is a chemical intermediate used in the paint and plastics industry. Inhalation of TMA can induce four types of syndromes in TMA workers; three are immunologically based whereas the fourth, an irritant syndrome, is nonimmunologic. To evaluate the potential inhalation hazard of TMA under controlled conditions, Sprague-Dawley rats were exposed 6 hr/day via inhalation to target concentrations of 0, 10, 30, 100, and 300 micrograms/m3 for varying durations. Two sets of rats received either 5 or 10 exposures and were terminated. A third set received 10 exposures, and was held 12 days and terminated. A fourth set received 10 exposures, and was held 12 days, challenged with a single 6-hr exposure, and terminated. A fifth set received 10 exposures, and was held 12 weeks and terminated. There were no effects after 5 exposures; however, after 10 exposures the following parameters were increased in a concentration-related manner: absolute and relative lung weights, external hemorrhagic lung foci, alveolar macrophage accumulation, alveolar hemorrhage, pneumonitis, and lung and mediastinal lymph node nonspecific IgG and complement (C3). The rats exposed and rested 12 days were nearly recovered from these effects; however, rats rested 12 days and subsequently challenged exhibited lesions similar to those seen immediately following exposure. Exposed rats rested 12 weeks were completely normal in all of the above parameters. The timing and nature of the lung lesions, along with the presence of lung IgG and complement, are consistent with some of the known aspects of TMA-induced lesions in humans, and are reflective of results obtained from other hypersensitivity pneumonitis models.