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93170 
Journal Article 
Inflammatory response of mice to manufactured titanium dioxide nanoparticles: Comparison of size effects through different exposure routes 
Grassian, VH; Adamcakoca-Dodd, A; Pettibone, JM; O'Shaughnessy, PI; Thorne, PS 
2007 
1 
Nanotoxicology
ISSN: 1743-5390
EISSN: 1743-5404 
Taylor & Francis, 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] 
1 
3 
211-226 
WOS:000260296700004 
TiO2 is a widely used manufactured nanomaterial and the opportunity for human exposure makes it necessary to study its health implications. Using murine models for inflammation, size effects of inflammatory response in instillation and acute inhalation exposures of TiO2 nanoparticles with manufacturers' average particles sizes of 5 and 21 nm were investigated. The properties of the primary nanoparticles, nanoparticle agglomerates, aerosol and instillation solution for both sized nanoparticles were evaluated. Mice were acutely exposed in a whole-body exposure chamber or through nasal instillation and toxicity was assessed by enumeration of total and differential cells, determination of total protein, LDH activity and inflammatory cytokines in BAL fluid. Lungs were also evaluated for histopathological changes. Results show the larger TiO2 nanoparticles were found to be moderately, but significantly, more toxic. The nanoparticles had different agglomeration states which may be a factor as important as the surface and physical characteristics of the primary nanoparticles in determining toxicity. 
Aerosol; inhalation; instillation; murine models; nanoparticle agglomeration; aggregation; titanium dioxide; inflammation