The effect of zirconium doping of cerium dioxide nanoparticles on pulmonary and cardiovascular toxicity and biodistribution in mice after inhalation

Research output: Contribution to journalArticlepeer-review

Authors

  • Susan Dekkers
  • Mark R. Miller
  • Roel P.F. Schins
  • Mike Russ
  • Rob J. Vandebriel
  • Marie France Belinga-Desaunay
  • Shea P. Connell
  • Ian P. Smith
  • Rodger Duffin
  • John A.F. Boere
  • Harm J. Heusinkveld
  • Harm J. Heusinkveld
  • Catrin Albrecht
  • Wim H. de Jong
  • Flemming R. Cassee
  • Flemming R. Cassee

External organisations

  • National Institute for Public Health and the Environment (RIVM)
  • EDINBURGH UNIVERSITY
  • IUF
  • Promethean Particles Ltd.
  • Utrecht University

Abstract

Development 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 (CeO 2 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 CeO 2 NPs with varying amounts of Zr-doping (0%, 27% or 78% Zr), or clean air, over a four-week period (4 mg/m 3 for 3 h/day, 5 days/week). Effects were assessed four weeks post-exposure. In all three mouse models CeO 2 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 CeO 2 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 CeO 2 NPs. These findings show that subacute inhalation of CeO 2 NPs causes minimal pulmonary and cardiovascular effect four weeks post-exposure and that Zr-doping of CeO 2 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.

Details

Original languageEnglish
Pages (from-to)794-808
Number of pages15
JournalNanotoxicology
Volume11
Issue number6
Early online date25 Jul 2017
Publication statusPublished - 9 Aug 2017

Keywords

  • cardiovascular, cerium dioxide, inhalation, Nanomaterials, redox activity