Comparative Toxicity of Standard Nickel and Ultrafine Nickel in Lung after Intratracheal Instillation

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Abstract
Comparative Toxicity of Standard Nickel and Ultrafine Nickel in Lung after Intratracheal Instillation: Qunwei Zhang, et al.; Department of Environmental Health, School of Medicine, Fukui Medical University—A comparison was made of the bronchoalveolar lavage fluid (BALF) response to ultrafine nickel (Uf‐Ni) and standard‐sized nickel (Std‐Ni). Rats were intratracheally instilled with 0, 0.1, 0.5, 1 and 5 mg Uf‐Ni and Std‐Ni, respectively. At 3 d after instillation, the body weight and wet lung weight were determined. At the same time, BALF was analyzed for lactate dehydrogenase (LDH), total protein (TP), tumor necrosis factor‐alpha (TNF‐alpha), 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 and Std‐Ni for each from 0 to 1 mg, and there were no differences in the indices between instillation of Uf‐Ni at 1 mg and 5 mg. The results also showed that the effects of Uf‐Ni on the indices were significantly higher than those of Std‐Ni. Additional groups of rats were intratracheally instilled with 1 mg of Uf‐Ni or Std‐Ni, and wet lung weight and BALF profiles were analyzed at 1, 3, 7, 15 and 30 d later. The effect of Uf‐Ni and Std‐Ni on indices that can be presumed to reflect epithelial injury and permeability (LDH or TP), and release of proinflammatory cytokine (TNF‐alpha) were increased throughout the 30 d post‐exposure and the effects of Uf‐Ni on these indices were significantly higher than those of Std‐Ni from 1 to 30 d after instillation. Moreover, the number of neutrophils and LDH activity in BALF of rats after exposure to Uf‐Ni were significantly greater than those of Std‐Ni‐exposed rats up to 30 d after instillation. Our findings suggest that Uf‐Ni has a much more toxic effect on the lung than St‐Ni, but the mechanism remains to be elucidated.