Evaluation of the effect of valence state on cerium oxide nanoparticle toxicity following intratracheal instillation in rats

Abstract

Cerium (Ce) is becoming a popular metal for use in electrochemical applications. When in the form of cerium oxide (CeO₂), Ce can exist in both 3 + and 4 + valence states, acting as an ideal catalyst. Previous in vitro and in vivo evidence have demonstrated that CeO₂ has either anti- or pro-oxidant properties, possibly due to the ability of the nanoparticles to transition between valence states. Therefore, we chose to chemically modify the nanoparticles to shift the valence state toward 3+. During the hydrothermal synthesis process, 10 mol% gadolinium (Gd) and 20 mol% Gd, were substituted into the lattice of the CeO₂ nanoparticles forming a perfect solid solution with various A-site valence states. These two Gd-doped CeO₂ nanoparticles were compared to pure CeO₂ nanoparticles. Preliminary characteristics indicated that doping results in minimal size and zeta potential changes but alters valence state. Following characterization, male Sprague-Dawley rats were exposed to 0.5 or 1.0 mg/kg nanoparticles via a single intratracheal instillation. Animals were sacrificed and bronchoalveolar lavage fluid and various tissues were collected to determine the effect of valence state and oxygen vacancies on toxicity 1-, 7-, or 84-day post-exposure. Results indicate that damage, as measured by elevations in lactate dehydrogenase, occurred within 1-day post-exposure and was sustained 7-day post-exposure, but subsided to control levels 84-day post-exposure. Furthermore, no inflammatory signaling or lipid peroxidation occurred following exposure with any of the nanoparticles. Our results implicate that valence state has a minimal effect on CeO₂ nanoparticle toxicity in vivo.

Keywords:

• Cerium oxide
• intratracheal instillation
• nanoparticles
• nanotoxicity
• valence state

Acknowledgements

The authors would like to thank Carrie Long and Dr. Nikki Marshall for insightful conversation about the project. Additionally, the authors would like to thank the histopathology research group at NIOSH for their assistance with tissue fixation and preparation and Shannon Case for her assistance with histopathology methods.

Declaration of interest

The authors report no conflict of interest. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health.

This project was funded by CDC/NIOSH/HELD Direct funding project (CAN 3927ZJUD). K.M.D. acknowledges support from the National Science Foundation through the IGERT program under grant number, DGE-1144676.

Supplementary material available online

Supplementary Figure S1