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Engineered titanium dioxide nanowire toxicity in vitro and in vivo.

Authors
Porter-DW; Holian-A; Sriram-K; Wu-N; Wolfarth-M; Hamilton-R; Buford-M
Source
Toxicologist 2008 Mar; 102(1):306
NIOSHTIC No.
20033627
Abstract
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.
Keywords
Particulates; Particulate-dust; Cell-biology; Biological-factors; Biological-monitoring; Biological-effects; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Pulmonary-disorders; Pulmonary-system-disorders; Pulmonary-system; Laboratory-animals; Brain-disorders; Brain-function; Breathing; Immune-system-disorders; Immunotoxins; Nanotechnology
CAS No.
1344-28-1
Publication Date
20080301
Document Type
Abstract
Fiscal Year
2008
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
1096-6080
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington
State
WV; MT; WA
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