Pulmonary toxicity to intratracheally administered indium trichloride in Fischer 344 rats.
The use of indium by the semiconductor industry has risen sharply in recent years with the discovery that the electrical properties of compounds such as indium phosphide and indium arsenide are better than those of silicon. However, relatively little is known about its potential to induce lung damage. These studies examined the effect of indium trichloride (InCl3) on the lung. To examine the disposition and removal of InCl3 from the lung, groups of female Fischer 344 rats received a single intratracheal dose of 1.3 mg In/kg as InCl3 and were euthanized after 1, 2, 4, 7, 14, 28, and 56 days at which time lung samples were analyzed for metal content. Furthermore, the histology, hydroxyproline levels, and bronchoalveolar lavage (BAL) fluid cellularity of the lung were studied. In addition, the effect of 0.00016, 0.00325, 0.065, and 1.3 mg In/kg on inflammatory response and BAL fluid cellularity was compared. While a dose as low as 0.00325 mg In/kg was capable of initiating an influx of inflammatory cells, instillation of 1.3 mg In/kg resulted in an inflammatory response that was still evident 56 days later. After 28 days, the lung weight of the InCl3-treated animals was 2.5 times greater than that of the controls. The total cell number in the BAL fluid of the treated animals after 28 days was 32 times higher than that in the control rats. Sixty-seven percent of these cells were granulocytes. Compared to the controls, the hydroxyproline content of the lungs from the InCl3-treated animals were two-fold greater after 28 and 56 days. Furthermore, the levels of fibronectin and TNF alpha present in the BAL fluid of InCl3-treated rats increased sharply during the first 24 hr and remained elevated 56 days later. These data and the histological examination of the lung following InCl3 treatment suggest that InCl3 is capable of causing severe lung damage and the development of fibrosis.
Blazka
M E
ME
Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Dixon
D
D
Haskins
E
E
Rosenthal
G J
GJ
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D007204:Indium / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013054:Spectrophotometry, Atomic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D005353:Fibronectins; D014409:Tumor Necrosis Factor-alpha; D007204:Indium; C020758:indium trichloride; D006909:Hydroxyproline