| Inhalation Exposure Study of Titanium Dioxide Nanoparticles with a Primary Particle Size of 2 to 5 nm Vicki H. Grassian,1,2,3, Patrick T. O'Shaughnessy,3 Andrea Adamcakova-Dodd,3 John M. Pettibone,2 and Peter S. Thorne3 1Departments of Chemistry, 2Chemical and Biochemical Engineering, and 3Occupational and Environmental Health, University of Iowa, Iowa City, Iowa, USA Abstract
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. Objectives: Titanium dioxide (TiO2) 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. Materials and Methods: The properties of TiO2 nanoparticles as well as the characteristics of aerosols of these particles were evaluated. Mice were exposed to TiO2 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/m3 nanoparticles demonstrated minimal lung toxicity or inflammation. Mice exposed subacutely (8.88 mg/m3) 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 TiO2 nanoparticles showed a significant but moderate inflammatory response among animals at week 0, 1, or 2 after exposure that resolved by week 3 postexposure. Key words: aerosol, inhalation toxicology study, murine models, nanoparticles, nanotoxicity, particle aggregation, surface area, titanium dioxide. Environ Health Perspect 115:397–402 (2007) . doi:10.1289/ehp.9469 available via http://dx.doi.org/ [Online 4 December 2006]
Address correspondence to V. Grassian, Department of Chemistry, University of Iowa, Iowa City, IA 52242 USA. Telephone: (310) 335-1392. Fax: (319) 335-1270. E-mail: vicki-grassian@uiowa.edu Although the research described in this article has been funded wholly or in part by the U.S. Environmental Protection Agency (EPA) through grant number EPA RD-83171701-0 to V.H.G., P.T.O., and P.S.T., it has not been subjected to the Agency's required peer and policy review and therefore does not necessarily reflect the views of the Agency and no official endorsement should be inferred. The National Institute of Environmental Health Sciences supported the pulmonary toxicology facility through National Institutes of Health grant P30 ES05605. V.H.G. is paid a consulting fee as a member of the science advisory board of Nanoscale Materials Inc. of Manhattan, Kansas, and owns stock shares in that company. All other authors declare no competing financial interest.
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