Pulmonary toxicity of inhaled nano-sized cerium oxide aerosols in Sprague–Dawley rats

Chang Guo*, Sarah Robertson, Ralf J.M. Weber, Alison Buckley, James Warren, Alan Hodgson, Joshua Z. Rappoport, Konstantin Ignatyev, Kirsty Meldrum, Isabella Römer, Sameirah Macchiarulo, James Kevin Chipman, Tim Marczylo, Martin O. Leonard, Timothy W. Gant, Mark R. Viant, Rachel Smith

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Cerium oxide nanoparticles (CeO2NPs), used in some diesel fuel additives to improve fuel combustion efficiency and exhaust filter operation, have been detected in ambient air and concerns have been raised about their potential human health impact. The majority of CeO2NP inhalation studies undertaken to date have used aerosol particles of larger sizes than the evidence suggests are emitted from vehicles using such fuel additives. Hence, the objective of this study was to investigate the effects of inhaled CeO2NP aerosols of a more environmentally relevant size, utilizing a combination of methods, including untargeted multi-omics to enable the broadest possible survey of molecular responses and synchrotron X-ray spectroscopy to investigate cerium speciation. Male Sprague–Dawley rats were exposed by nose-only inhalation to aerosolized CeO2NPs (mass concentration 1.8mg/m3, aerosol count median diameter 40nm) for 3h/d for 4 d/week, for 1 or 2 weeks and sacrificed at 3 and 7d post-exposure. Markers of inflammation changed significantly in a dose- and time-dependent manner, which, combined with results from lung histopathology and gene expression analyses suggest an inflammatory response greater than that seen in studies using micron-sized ceria aerosols. Lipidomics of lung tissue revealed changes to minor lipid species, implying specific rather than general cellular effects. Cerium speciation analysis indicated a change in Ce3+/Ce4+ ratio within lung tissue. Collectively, these results in conjunction with earlier studies emphasize the importance of aerosol particle size on toxicity determination. Furthermore, the limited effect resolution within 7d suggested the possibility of longer-term effects.

Original languageEnglish (US)
Pages (from-to)733-750
Number of pages18
Issue number6
StatePublished - Jul 3 2019


  • Nanoparticle
  • cerium
  • inhalation
  • omics
  • rat

ASJC Scopus subject areas

  • Biomedical Engineering
  • Toxicology


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