Toxicological evaluation of lung responses after intratracheal exposure to non-dispersed titanium dioxide nanorods

J Toxicol Environ Health A. 2011;74(12):790-810. doi: 10.1080/15287394.2011.567954.


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 × 10(5) 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.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Inhalation
  • Animals
  • Dose-Response Relationship, Drug
  • Inhalation Exposure*
  • Listeria monocytogenes / drug effects
  • Listeria monocytogenes / growth & development
  • Listeria monocytogenes / metabolism
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Nanostructures / chemistry
  • Nanostructures / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Silicon Dioxide / toxicity
  • Titanium / toxicity*


  • titanium dioxide
  • Silicon Dioxide
  • Titanium