Toxicological Evaluation of Lung Responses After Intratracheal Exposure to Non-Dispersed Titanium Dioxide Nanorods.

Fine- and coarse-sized titanium dioxide (TiO2) particles are considered to be relatively inert when inhaled. The goal of this study was to assess potential lung toxicity associated with well-characterized, non-dispersed rutile TiO2 nanorods (10 × 40 nm). In vitro bioreactivity of TiO2 nanorods was determined by electron spin resonance (ESR) to measure free radical production. To assess pulmonary effects in vivo, Sprague-Dawley rats were intratracheally instilled with saline, silica, or TiO2 nanorods (10 μg, 100 μg, or 1 mg/rat). On d 1, 3, and 6 posttreatment, left lungs were preserved for microscopy and histopathology, and lung lavage was performed on right lungs. Additional rats were treated with saline or TiO2 nanorods (100 μg or 1 mg/rat) on d 0, intratracheally inoculated with 5 × 105 Listeria monocytogenes on d 3, and bacterial clearance was assessed. ESR showed a significant concentration-dependent generation of hydroxyl radicals by TiO2 nanorods in the presence and absence of macrophages; however, the hydroxyl radical signals from TiO2 samples were low compared to silica. Rats exposed to 1 mg of TiO2 nanorods had significantly elevated levels of lung injury, inflammation, and lavage fluid monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-2 on d 1 and 3 that subsided by d 6, unlike the silica response that persisted. Immune cytokine secretion in the lung and bacterial clearance were not affected by preexposure to TiO2 nanorods. To summarize, non-dispersed TiO2 nanorods were found to induce radical formation and cellular oxidant production, and to generate transient and reversible pneumotoxic effects, and to not markedly alter pulmonary immune function. [ABSTRACT FROM AUTHOR]