Inflammatory response of mice to manufactured titanium dioxide nanoparticles: Comparison of size effects through different exposure routes

Abstract

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

Acknowledgements

Although the research described in this article has been funded wholly or in part by the Environmental Protection Agency through grant number EPA RD-83171701-0 to VHG, PTO and PST, 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. NIEHS supported the Pulmonary Toxicology Facility through NIH P30 ES05605. Competing financial interest statement: Vicki H. Grassian is paid a consulting fee as a member of the science advisory board of Nanoscale Materials Inc. of Manhattan, Kansas, USA, and owns stock shares in that company. All of the other authors declare they have no competing financial interests.