Toxicity of gallium oxide particles following a 4-week inhalation exposure

To evaluate the inhalation toxicity of Ga2O3, F344 rats were exposed nose-only to 0.2 micron Ga2O3 particles 2 h/day, 5 days/week for 4 weeks. The exposure concentration was 23 +/- 5 mg/m3 (mean +/- SD) resulting in lung burdens of 0.8 +/- 0.1 mg Ga2O3/lung (mean +/- SE) at the end of 4 weeks of exposure. Analysis of bronchoalveolar lavage fluid of exposed rats showed marked responses. One day after termination of exposure, lactate dehydrogenase was increased 6-fold, and the lysosomal enzyme, beta-glucuronidase, was increased 38-fold in rats exposed to Ga2O3 compared to sham exposed controls. Alkaline phosphatase, glutathione reductase, glutathione peroxidase, white blood cells, acid proteinase, and protein were increased 3- to 4-fold. Responses remained elevated 6 and 12 months after exposure. Lung clearance of radiolabeled tracer particles was evaluated 4 days and 6 months after the end of 4 weeks of Ga2O3 exposures. Long-term clearance half-times were significantly longer (3-4 fold, P less than 0.01) in rats exposed to Ga2O3 than in the sham-exposed control rats at both 4 days and 6 months, indicating persistent impairment of particle clearance. Histopathological lesions consisted primarily of alveolar proteinosis 1 day after 4 weeks exposure, progressing in severity to large focal lesions of alveolar histiocytosis and septal fibrosis 6 and 12 months after exposure. Inhaled Ga2O3 produced cytotoxic, inflammatory, and fibrogenic responses of comparable or greater magnitude than those seen after similar exposures of rats to inhaled quartz particles in other studies. These data show that inhaled Ga2O3 particles produce considerable toxicity and exposures in the work place should be limited.