TY - JOUR
T1 - Pulmonary toxicity of inhaled nano-sized cerium oxide aerosols in Sprague–Dawley rats
AU - Guo, Chang
AU - Robertson, Sarah
AU - Weber, Ralf J.M.
AU - Buckley, Alison
AU - Warren, James
AU - Hodgson, Alan
AU - Rappoport, Joshua Z.
AU - Ignatyev, Konstantin
AU - Meldrum, Kirsty
AU - Römer, Isabella
AU - Macchiarulo, Sameirah
AU - Chipman, James Kevin
AU - Marczylo, Tim
AU - Leonard, Martin O.
AU - Gant, Timothy W.
AU - Viant, Mark R.
AU - Smith, Rachel
N1 - Funding Information:
This study was funded by the UK’s Natural Environment Research Council and Medical Research Council as part of the FABLE project (From Airborne exposures to BioLogical Effects) (NE/I008314), with support from Public Health England.
Funding Information:
The authors thank Dr Jennifer Kirwan and Lorraine Wallace (University of Birmingham) for assistance with the multi-omics data collection. Transmission electron microscopy was performed by Mr Lennell Reynolds at the Northwestern University Center for Advanced Microscopy, generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. The authors thank Diamond Light Source for access to beamline I18 (proposal SP12583-1) that contributed to the results presented here.
Funding Information:
This study was funded by the UK?s Natural Environment Research Council and Medical Research Council as part of the FABLE project (From Airborne exposures to BioLogical Effects) (NE/I008314), with support from Public Health England. The authors thank Dr Jennifer Kirwan and Lorraine Wallace (University of Birmingham) for assistance with the multi-omics data collection. Transmission electron microscopy was performed by Mr Lennell Reynolds at the Northwestern University Center for Advanced Microscopy, generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. The authors thank Diamond Light Source for access to beamline I18 (proposal SP12583-1) that contributed to the results presented here.
Publisher Copyright:
© 2019, © 2019 Crown Copyright. Reproduced with the permission of Public Health England. Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2019/7/3
Y1 - 2019/7/3
N2 - 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.
AB - 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.
KW - Nanoparticle
KW - cerium
KW - inhalation
KW - omics
KW - rat
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UR - http://www.scopus.com/inward/citedby.url?scp=85060850880&partnerID=8YFLogxK
U2 - 10.1080/17435390.2018.1554751
DO - 10.1080/17435390.2018.1554751
M3 - Article
C2 - 30704321
AN - SCOPUS:85060850880
SN - 1743-5390
VL - 13
SP - 733
EP - 750
JO - Nanotoxicology
JF - Nanotoxicology
IS - 6
ER -
