Toxicity of ultrafine nickel particles in lungs after intratracheal instillation

To study the lung acute and subacute toxicity of ultrafine nickel particles, rats were intratracheally instilled with 0, 0.1, 0.5, 1 and 5 mg ultrafine nickel (Uf-Ni), respectively. At 3 days after injection, the body weight and wet lung weight were determined. At the same time, bronchoalveolar lavage fluid (BALF) was analyzed for lactate dehydrogenase (LDH), total protein (TP), and total cell and differential cell counts. The results showed that indicators of lung injury and inflammation in BALF were markedly raised with increased Uf-Ni from 0 to I mg, and there were no differences in the indices between injection of Uf-Ni at 1 mg and at 5 mg. Rats were intratracheally instilled with 1 mg Uf-Ni, and wet lung weight, and bronchoalveolar lavage fluid (BALF) profiles were analyzed 1, 3, 7, 15 and 30 days later. The effects of Uf-Ni on indices that can be presumed to reflect epithelial injury and permeability (LDH or TP) were dramatically increased from day 1 up to 30 days after injection. Lung histology findings generally confirmed the BALF data, showing severe lung inflammation at 1 day after injection of Uf-Ni, and epithelial hyperplasia and inflammation still present at 30 days after injection. Our findings suggest that Uf-Ni causes persistent inflammation following instillation of a small dose.