Inhalation exposure study of titanium dioxide nanoparticles with a primary particle size of 2 to 5 nm.
BACKGROUND
Nanotechnology offers great promise in many industrial applications. However, little is known about the health effects of manufactured nanoparticles, the building blocks of nanomaterials.


OBJECTIVE
Titanium dioxide (TiO(2)) nanoparticles with a primary size of 2-5 nm have not been studied previously in inhalation exposure models and represent some of the smallest manufactured nanoparticles. The purpose of this study was to assess the toxicity of these nanoparticles using a murine model of lung inflammation and injury.


METHODS
The properties of TiO(2) nanoparticles as well as the characteristics of aerosols of these particles were evaluated. Mice were exposed to TiO(2) nanoparticles in a whole-body exposure chamber acutely (4 hr) or subacutely (4 hr/day for 10 days). Toxicity in exposed mice was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase (LDH) activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid. Lungs were also evaluated for histopathologic changes


RESULTS
Mice exposed acutely to 0.77 or 7.22 mg/m(3) nanoparticles demonstrated minimal lung toxicity or inflammation. Mice exposed subacutely (8.88 mg/m(3)) and necropsied immediately and at week 1 or 2 postexposure had higher counts of total cells and alveolar macrophages in the BAL fluid compared with sentinels. However, mice recovered by week 3 postexposure. Other indicators were negative.


CONCLUSIONS
Mice subacutely exposed to 2-5 nm TiO(2) nanoparticles showed a significant but moderate inflammatory response among animals at week 0, 1, or 2 after exposure that resolved by week 3 postexposure.
Grassian
Vicki H
VH
Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, USA. vicki-grassian@uiowa.edu
O'shaughnessy
Patrick T
PT
Adamcakova-Dodd
Andrea
A
Pettibone
John M
JM
Thorne
Peter S
PS
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D019570:Inhalation Exposure; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D010316:Particle Size; D014025:Titanium / Q000008:administration & dosage / Q000633:toxicity*
D016207:Cytokines; C009495:titanium dioxide; D014025:Titanium