title: Toxicological evaluation of lung responses after intratracheal exposure to non-dispersed titanium dioxide nanorods.
abstract: 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.
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA. jur6@cdc.gov
authors.forename: Jenny R
authors.initials: JR
authors.lastname: Roberts
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Chapman
authors.forename: Vijay R
authors.initials: VR
authors.lastname: Tirumala
authors.forename: Alamgir
authors.initials: A
authors.lastname: Karim
authors.forename: Bean T
authors.initials: BT
authors.lastname: Chen
authors.forename: Diane
authors.initials: D
authors.lastname: Schwegler-Berry
authors.forename: Aleksandr B
authors.initials: AB
authors.lastname: Stefaniak
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Leonard
authors.forename: James M
authors.initials: JM
authors.lastname: Antonini
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D004305:Dose-Response Relationship, Drug; D019570:Inhalation Exposure; D008089:Listeria monocytogenes / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D049329:Nanostructures / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000633:toxicity; D014025:Titanium / Q000633:toxicity*
chemical_list: C009495:titanium dioxide; D012822:Silicon Dioxide; D014025:Titanium