Premium
Toxicity of gallium oxide particles following a 4‐week inhalation exposure
Author(s) -
Wolff R. K.,
Henderson R. F.,
Eidson A. F.,
Pickrell J. A.,
Rothenberg S. J.,
Hahn F. F.
Publication year - 1988
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550080307
Subject(s) - toxicity , bronchoalveolar lavage , inhalation , lactate dehydrogenase , inhalation exposure , pulmonary alveolar proteinosis , lung , endocrinology , medicine , glutathione , chemistry , pulmonary toxicity , pathology , anesthesia , enzyme , biochemistry
To evaluate the inhalation toxicity of Ga 2 O 3 , F344 rats were exposed nose‐only to 0.2 μm Ga 2 O 3 particles 2 h/day, 5 days/week for 4 weeks. The exposure concentration was 23 ± 5 mg/m 3 (mean ± SD) resulting in lung burdens of 0.8 ± 0.1 mg Ga 2 O 3 /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 Ga 2 O 3 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 Ga 2 O 3 exposures. Long‐term clearance half‐times were significantly longer| (3–4 fold, P <0.01) in rats exposed to Ga 2 O 3 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 Ga 2 O 3 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 Ga 2 O 3 particles produce considerable toxicity and exposures in the work place should be limited.