The potential for pulmonary toxicity of nanoparticles after respiratory exposure may depend on particle size, shape, composition, and reactivity. The goal of this study was to characterize lung toxicity and inflammation associated with non-dispersed titanium nanorods (TiO2), a particle considered to be relatively inert at larger sizes. The reactivity of rutile TiO2 nanorods (10 x 40 nm) was assessed by electron spin resonance (ESR). Also, ESR was performed on rat alveolar macrophages (AMs) that had been treated for 3 min with TiO2 nanorods in vitro (10 microg, 50 microg, 100 microg, or 1 mg) or a positive control (silica) to measure particle-induced radical production. To assess the pulmonary effects in vivo, male Sprague-Dawley rats were intratracheally instilled (IT) with saline or TiO2 nanorods (10 microg, 100 microg, or 1 mg per rat). On days 1, 3, and 6 post-IT, the left lungs of rats were preserved for EM and histopathological analysis, and bronchoalveolar lavage (BAL) was performed on right lungs to retrieve cells and fluid for analysis. ESR showed a significant dose-dependent presence of hydroxyl radicals in the TiO2 samples, and a dose-dependent production of hydroxyl radicals in AMs stimulated with the particles when compared to controls; however, the hydroxyl radical signals of the TiO2 samples were low compared to the positive control. In vivo, rats treated with 1 mg of TiO2 nanorods had significantly elevated levels of lung cytotoxicty, neutrophil influx, cellular oxidant production, and inflammatory cytokines and chemokines (IL-6, MCP-1, and MIP-2) on days 1 and 3. Rats exposed to 100 microg of TiO2 nanorods also had significant increases in the same indicators of cytotoxicty, inflammation, and oxidative stress when compared to controls on day 1, although to a lesser degree than the 1 mg group. To summarize, the non-dispersed TiO2 nanorods were found to induce radical formation and oxidant production, and were acutely cytotoxic and inflammatory in the lung. Future studies will assess these responses using dispersed TiO2 nanorods.
Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Pulmonary-disorders; Pulmonary-system-disorders; Pulmonary-system; Laboratory-animals; Breathing; Inhalation-studies; Lung-cells; Fibrogenicity; Fibrous-bodies; Fibrogenesis; Particulates; Particulate-dust; Cytotoxic-effects; Oxidative-metabolism; Nanotechnology
The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington