Pulmonary toxicity following an intratracheal instillation of nickel oxide nanoparticle agglomerates.

OBJECTIVE We examined the pulmonary toxicity of nickel oxide nanoparticle agglomerates in the rat lung following an intratracheal instillation. METHODS The weighted average surface primary diameter of nickel oxide nanoparticles was 8.41 nm, and the count median diameter of nickel oxide nanoparticle agglomerates suspended in saline was 1.34 µm. Male Wistar rats were exposed to 1 mg (3.3 mg/kg) of nickel oxide nanoparticles intratracheally. The control group received intratracheal instillation of saline. Rats were dissected 3 days, 1 wk, 1 mo, 3 mo, and 6 mo after the instillation. Cytokine-induced neutrophil chemoattractant (CINC)-2αβ in the lung tissue was determined by quantitative measurement of protein by ELISA. RESULTS The total cell count in bronchoalveolar lavage fluid (BALF) was increased persistently from 3 days to 6 mo. The neutrophil counts in BALF were also increased at 3 days, 1 wk, 3 mo, and 6 mo. In the lung tissue, infiltration of mainly neutrophils and alveolar macrophages was observed in alveoli from 3 days to 6 mo. The CINC-2αβ concentration was elevated from 3 days to 6 mo in the lung tissue. CONCLUSIONS These results showed that micron-sized nickel oxide nanoparticle agglomerates also induced a persistent inflammatory response.