Engineered Titanium Dioxide Nanowire Toxicity In Vitro and In Vivo

Details

• Personal Author:
  Buford M ; Hamilton R ; Holian A ; Porter DW ; Sriram K ; Wolfarth M ; Wu N
• Description:
  While the application and benefits of manufacturing nanowires is highly promising, their adverse effects have not been fully investigated. For these studies, TiO2 nanowires (anatase, diameter=80 nm, length=20-25 microm) were synthesized using sol-gel process directed by a porous anodic aluminum oxide template. We conducted in vitro studies using alveolar macrophages isolated from both C57Bl/6 and Balb/c mice assessing toxicity with 4 hr suspension incubations by trypan blue exclusion and apoptosis using Cell Death ELISA. TiO2 nanospheres caused no toxicity or apoptosis up to 200 microg/ml. In contrast, TiO2 nanowires caused significant and marked dose-dependent toxicity and increase in apoptosis. Furthermore, TiO2 nanowires, but not nanospheres increased alveolar macrophage antigen presenting activity (using ovalbumin and T cells from DO11.10 mice) to similar extents as the potent particle crystalline silica. For in vivo studies we exposed C57Bl/6 mice by pharyngeal aspiration to TiO2 nanowires (0-80 microg/mouse) and examined lung and brain responses at one day post-exposure. In the lung, exposure to TiO2 nanowires induced dose-dependent increases in the expression of the inflammatory mediators TNF-alpha (1.8- to 5-fold), MIP-2 (4- to 33-fold) and CCL2 (7- to 30-fold). In the brain, pulmonary exposure to TiO2 nanowires induced expression of the endothelial cell adhesion molecule E-selectin in olfactory bulb (4-6 fold), suggestive of altered blood brain barrier (BBB) permeability. Unlike the dose-dependent pulmonary effects, the neural responses were elicited only by higher doses of the nanowires. Whether the BBB changes observed are a consequence of the translocation of these nanoparticles to the brain or a systemic inflammatory response remains to be investigated. Taken together, the data suggest that exposure to TiO2 nanowires may result in adverse health outcomes. [Description provided by NIOSH]
• Subjects:
  Biological Factors Irritants Laboratories Lung Lung Diseases Nervous System Nervous System Diseases Occupational Health Particulate Matter Respiratory Hypersensitivity Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Biological-effects Biological-factors Biological-monitoring Brain-disorders Brain-function Breathing Cell-biology Immune-system-disorders Immunotoxins Laboratory-animals Nanotechnology Particulate-dust Particulates Pulmonary-disorders Pulmonary-system Pulmonary-system-disorders Respiratory-hypersensitivity Respiratory-irritants Respiratory-system-disorders

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Montana ; OSHA Region 10 ; OSHA Region 3 ; OSHA Region 8 ; Washington ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  102
• Issue:
  1
• NIOSHTIC Number:
  nn:20033627
• Citation:
  Toxicologist 2008 Mar; 102(1):306
• CAS Registry Number:
  Alumina (CAS RN 1344-28-1)
• Federal Fiscal Year:
  2008
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ee1eca8df58f4ef48e8c8a91a2175744f2c3ebe49ade678423987bb469df314270ea92ce1324dfdc00b151c65fefad8165807b2e16343ae3d06e1b267a982edd
• Download URL:
  https://stacks.cdc.gov/view/cdc/189113/cdc_189113_DS1.pdf
• File Type:
  [PDF - 7.72 MB ]