Effects of Intratracheally Administered Indium Phosphide on Male Fischer 344 Rats

Abstract

Effects of Intratracheally Administered Indium Phosphide on Male Fischer 344 Rats: Takamoto Uemura, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University—Objective—To examine the effects of intratracheally administered indium phosphide (InP) and distribution of indium on male Fischer 344 rats. Materials and methods—Rats were intratracheally given 0, 1, 10 or 100 mg/kg of InP with a mean diameter of 0.8pm and observed for 1 and 7 days. The bronchoalveolar lavage fluid (BALF) was examined biochemically and cytologically. Serum biochemical, hematological and histopathological examinations were done, and the indium concentration in organs and serum was determined. Findings—The number of neutrophils in BALF remarkably increased in a dose‐effect manner 1 and 7 days after administration and InP particles were phagocytized in the macrophages. Total protein (TP), lactate dehydrogenase (LDH), total phospholipid (TPL) and total cholesterol (T‐Cho) in BALF showed a clear dose‐effect relationship 7 days after administration. Indium was detected in the liver and spleen and increased in a dose‐related manner on the next day and 7 days after administration. Serum indium was detected in the group given more than 10 mg/kg but did not reveal a dose relationship. Histopathological examination of the lungs showed phagocytized InP particles in the macrophages and the migration of neutrophiles in the alveoli. InP particles remained in the bronchioles and alveoli until 7 days after. No histopathological changes were detected in the liver or spleen. A hematological study did not reveal significant findings, interpretation—Intratracheally administered InP particles cause pulmonary inflammation and those particles remain in the lower airways for at least 7 days. Phagocytosis of macrophages may contribute to their disposal and distribution to the liver and spleen. Further study is required with particles with a lower toxic activity than InP and with the same particle size as the InP used in this study, to clarify their specific toxicity. Simultaneously longer observation is needed to assess toxicity in the other organs after distribution.

Causal Relationship between Indium Compound Inhalation and Effects on the Lungs

“…It is well known that the inhalation of hardly soluble hazardous particles, such as crystalline silica, asbestos, and so on, induces pneumoconiosis. In animal experiments, intra-tracheal instillation of indium compounds induces pneumonitis, proliferation of fibrous tissues, pulmonary fibrosis, and other lung diseases [3][4][5][6] . The results of our study are consistent with these information.…”

“…Until the early 1990's, there was little information on the toxic effects of indium on humans or animals. In the mid 1990's, intra-tracheal instillation studies of particles of compound semiconductors such as indium phosphide, indium arsenide and indium trichloride revealed that metal compounds containing indium had a strong potential to induce severe lung damage [2][3][4][5][6] . In 2003, Homma et al 7) disclosed a case of interstitial pneumonia in a 27-yr-old male worker engaged in the wet surface polishing process of indium-tin oxide (ITO) target plates, high-density plates made of very hard ceramics composed of indium oxide and tin oxide, which are used to laminate transparent electroconductive thin-film on flat displays and solar cells.…”

Chronic Pulmonary Toxicity Study of Indium‐Tin Oxide and Indium Oxide Following Intratracheal Instillations into the Lungs of Hamsters

“…Due to the increasing production of ITO, the potential health hazards of occupational or environmental exposure to this material have began to cause great concern. Since the mid 1990's, data have become available indicating that indium compounds can be toxic to animals [2][3][4][5][6][7][8][9][10][11][12] , although there is little information regarding the adverse health effects for workers exposed to indium compounds. In 2003, the first case of interstitial pneumonia caused by occupational exposure to ITO was reported 13) .…”

Biological Monitoring of Indium by Means of Graphite Furnace Atomic Absorption Spectrophotometry in Workers Exposed to Particles of Indium Compounds

“…From the mid-1990s, animal experiments have shown that the inhalation or intratracheal instillation of In compounds causes severe lung inflammation [1][2][3][4][5][6][7] and mild adverse reproductive effects [8][9][10] . Although the health effects of In on workers' respiratory and reproductive systems have been unclear to date, assessing the exposure-effect relationships in Inexposed workers is a serious concern, but no information is available on the exposure-effect relationships in workers.…”