Toxicological evaluation of lung responses after intratracheal exposure to non-dispersed titanium dioxide nanorods.
Roberts-JR; Chapman-RS; Tirumala-VR; Karim-A; Chen-BT; Schwegler-Berry-D; Stefaniak-AB; Leonard-SS; Antonini-JM
J Toxicol Environ Health, A 2011 May; 74(12):790-810
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 x 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 ug, 100 ug, 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 ug or 1 mg/rat) on d 0, intratracheally inoculated with 5 x 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 TiO(2) nanorods. To summarize, non-dispersed TiO(2) 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.
Alveolar-cells; Animal-studies; Biological-effects; Biological-systems; Immune-reaction; Laboratory-animals; Laboratory-testing; Lung-disorders; Lung-irritants; Microscopic-analysis; Nanotechnology; Particle-aerodynamics; Particulates; Physiological-effects; Physiological-response; Pulmonary-system; Pulmonary-system-disorders; Quantitative-analysis; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Tissue-disorders; Toxic-effects; Toxicology
Jenny R. Roberts, PhD, Health Effects Laboratory Division, National Institute for Occupational Safety and Health (NIOSH), 1095 Willowdale Rd. (M/S 2015), Morgantown, WV 26505, USA
Journal of Toxicology and Environmental Health, Part A: Current Issues