Inflammatory response of mice following inhalation exposure to iron and copper nanoparticles

Abstract

We examined pulmonary inflammatory responses of mice following whole-body inhalation exposure to copper and iron nanoparticles in acute and sub-acute studies. Concentrations for sub-acute copper and iron exposures were 3.6 mg m⁻³. No significant pathology was found following acute exposure. Immediately following sub-acute exposure, both iron- and copper-exposed mice showed increased inflammation compared to sentinels. Copper nanoparticle-exposed mice had significantly higher lavage cytokines as well as perivasculitis and alveolitis. Three weeks post-exposure, all inflammatory markers decreased for iron nanoparticle-exposed mice, however, some remained elevated for copper-exposed mice. At biologically relevant pHs, in vitro studies showed that copper nanoparticles displayed a greater propensity for dissolution compared to iron. We conclude that the presence of dissolved ions, the concomitant formation of smaller nanoparticles and the absence of particles in stained lung sections immediately postexposure (inferring either translocation or more dispersed aerosol distribution) contributed to the increased inflammation observed in copper nanoparticle-exposed mice.

• Aerosol
• inhalation
• murine models
• dissolution
• copper
• iron
• nanoparticles
• agglomerates

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. NIOSH support is also acknowledged through R01 OH009448-01. 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 Northern Nanotech Inc. Toronto, Canada, and Nanoscale Materials Inc. of Manhattan, Kansas, and owns stock shares in that company. All of the other authors declare they have no competing financial interests. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.