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

DOI: 10.1080/17435390.2018.1554751 DOI Help

Authors: Chang Guo (Public Health England) , Sarah Robertson (Public Health England) , Ralf J. M. Weber (University of Birmingham) , Alison Buckley (Public Health England) , James Warren (Public Health England) , Alan Hodgson (Public Health England) , Joshua Z. Rappoport (Northwestern University) , Konstantin Ignatyev (Diamond Light Source) , Kirsty Meldrum (Public Health England) , Isabella Römer (Public Health England) , Sameirah Macchiarulo (Public Health England) , James Kevin Chipman (University of Birmingham) , Tim Marczylo (Public Health England) , Martin O. Leonard (Public Health England) , Timothy W. Gant (Public Health England) , Mark R. Viant (University of Birmingham) , Rachel Smith (Public Health England)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nanotoxicology , VOL 8 , PAGES 1 - 18

State: Published (Approved)
Published: February 2019
Diamond Proposal Number(s): 12583

Open Access Open Access

Abstract: 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 1.8 mg/m3, aerosol count median diameter 40 nm) for 3 h/d for 4 d/week, for 1 or 2 weeks and sacrificed at 3 and 7 d 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 7 d suggested the possibility of longer-term effects.

Journal Keywords: particle; cerium; omics; rat; inhalation

Subject Areas: Biology and Bio-materials, Environment, Chemistry

Instruments: I18-Microfocus Spectroscopy