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dc.contributor.authorDekkers, Susan
dc.contributor.authorMiller, Mark R
dc.contributor.authorSchins, Roel P F
dc.contributor.authorRömer, Isabella
dc.contributor.authorRuss, Mike
dc.contributor.authorVandebriel, Rob J
dc.contributor.authorLynch, Iseult
dc.contributor.authorBelinga-Desaunay, Marie-France
dc.contributor.authorValsami-Jones, Eugenia
dc.contributor.authorConnell, Shea P
dc.contributor.authorSmith, Ian P
dc.contributor.authorDuffin, Rodger
dc.contributor.authorBoere, John A F
dc.contributor.authorHeusinkveld, Harm J
dc.contributor.authorAlbrecht, Catrin
dc.contributor.authorde Jong, Wim H
dc.contributor.authorCassee, Flemming R
dc.date.accessioned2018-01-09T09:20:11Z
dc.date.available2018-01-09T09:20:11Z
dc.date.issued2017-08
dc.identifier.citationThe effect of zirconium doping of cerium dioxide nanoparticles on pulmonary and cardiovascular toxicity and biodistribution in mice after inhalation. 2017, 11 (6):794-808 Nanotoxicologyen
dc.identifier.issn1743-5404
dc.identifier.pmid28741972
dc.identifier.doi10.1080/17435390.2017.1357214
dc.identifier.urihttp://hdl.handle.net/10029/621043
dc.description.abstractDevelopment and manufacture of nanomaterials is growing at an exponential rate, despite an incomplete understanding of how their physicochemical characteristics affect their potential toxicity. Redox activity has been suggested to be an important physicochemical property of nanomaterials to predict their biological activity. This study assessed the influence of redox activity by modification of cerium dioxide nanoparticles (CeO2 NPs) via zirconium (Zr) doping on the biodistribution, pulmonary and cardiovascular effects in mice following inhalation. Healthy mice (C57BL/6 J), mice prone to cardiovascular disease (ApoE-/-, western-diet fed) and a mouse model of neurological disease (5 × FAD) were exposed via nose-only inhalation to CeO2 NPs with varying amounts of Zr-doping (0%, 27% or 78% Zr), or clean air, over a four-week period (4 mg/m3 for 3 h/day, 5 days/week). Effects were assessed four weeks post-exposure. In all three mouse models CeO2 NP exposure had no major toxicological effects apart from some modest inflammatory histopathology in the lung, which was not related to the amount of Zr-doping. In ApoE-/- mice CeO2 did not change the size of atherosclerotic plaques, but there was a trend towards increased inflammatory cell content in relation to the Zr content of the CeO2 NPs. These findings show that subacute inhalation of CeO2 NPs causes minimal pulmonary and cardiovascular effect four weeks post-exposure and that Zr-doping of CeO2 NPs has limited effect on these responses. Further studies with nanomaterials with a higher inherent toxicity or a broader range of redox activities are needed to fully assess the influence of redox activity on the toxicity of nanomaterials.
dc.language.isoenen
dc.rightsArchived with thanks to Nanotoxicologyen
dc.subject.meshAnimals
dc.subject.meshCardiovascular System
dc.subject.meshCerium
dc.subject.meshInhalation Exposure
dc.subject.meshLung
dc.subject.meshMice
dc.subject.meshMice, Inbred C57BL
dc.subject.meshMice, Knockout, ApoE
dc.subject.meshNanoparticles
dc.subject.meshOxidation-Reduction
dc.subject.meshPlaque, Atherosclerotic
dc.subject.meshTissue Distribution
dc.subject.meshZirconium
dc.titleThe effect of zirconium doping of cerium dioxide nanoparticles on pulmonary and cardiovascular toxicity and biodistribution in mice after inhalation.en
dc.typeArticleen
dc.identifier.journalNanotoxicology 2017, 11(6):794-808en
html.description.abstractDevelopment and manufacture of nanomaterials is growing at an exponential rate, despite an incomplete understanding of how their physicochemical characteristics affect their potential toxicity. Redox activity has been suggested to be an important physicochemical property of nanomaterials to predict their biological activity. This study assessed the influence of redox activity by modification of cerium dioxide nanoparticles (CeO2 NPs) via zirconium (Zr) doping on the biodistribution, pulmonary and cardiovascular effects in mice following inhalation. Healthy mice (C57BL/6 J), mice prone to cardiovascular disease (ApoE-/-, western-diet fed) and a mouse model of neurological disease (5 × FAD) were exposed via nose-only inhalation to CeO2 NPs with varying amounts of Zr-doping (0%, 27% or 78% Zr), or clean air, over a four-week period (4 mg/m3 for 3 h/day, 5 days/week). Effects were assessed four weeks post-exposure. In all three mouse models CeO2 NP exposure had no major toxicological effects apart from some modest inflammatory histopathology in the lung, which was not related to the amount of Zr-doping. In ApoE-/- mice CeO2 did not change the size of atherosclerotic plaques, but there was a trend towards increased inflammatory cell content in relation to the Zr content of the CeO2 NPs. These findings show that subacute inhalation of CeO2 NPs causes minimal pulmonary and cardiovascular effect four weeks post-exposure and that Zr-doping of CeO2 NPs has limited effect on these responses. Further studies with nanomaterials with a higher inherent toxicity or a broader range of redox activities are needed to fully assess the influence of redox activity on the toxicity of nanomaterials.


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