Environmentally relevant iron oxide nanoparticles produce limited acute pulmonary effects in rats at realistic exposure levels

Chang Guo*, Ralf J.M. Weber, Alison Buckley, Julie Mazzolini, Sarah Robertson, Juana Maria Delgado-Saborit, Joshua Z. Rappoport, James Warren, Alan Hodgson, Paul Sanderson, James Kevin Chipman, Mark R. Viant, Rachel Smith

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Iron is typically the dominant metal in the ultrafine fraction of airborne particulate matter. Various studies have investigated the toxicity of inhaled nano-sized iron oxide particles (FeOx NPs) but their results have been contradictory, with some indicating no or minor effects and others finding effects including oxidative stress and inflammation. Most studies, however, did not use materials reflecting the characteristics of FeOx NPs present in the environment. We, therefore, analysed the potential toxicity of FeOx NPs of different forms (Fe3 O4, α-Fe2 O3 and γ-Fe2 O3) reflecting the characteristics of high iron content nano-sized particles sampled from the environment, both individually and in a mixture (FeOx-mix). A preliminary in vitro study indicated Fe3 O4 and FeOx-mix were more cytotoxic than either form of Fe2 O3 in human bronchial epithelial cells (BEAS-2B). Follow-up in vitro (0.003, 0.03, 0.3 µg/mL, 24 h) and in vivo (Sprague–Dawley rats, nose-only exposure, 50 µg/m3 and 500 µg/m3, 3 h/d × 3 d) studies therefore focused on these materials. Experiments in vitro explored responses at the molecular level via multi-omics analyses at concentrations below those at which significant cytotoxicity was evident to avoid detection of responses secondary to toxicity. Inhalation experiments used aerosol concentrations chosen to produce similar levels of particle deposition on the airway surface as were delivered in vitro. These were markedly higher than environmental concentrations. No clinical signs of toxicity were seen nor effects on BALF cell counts or LDH levels. There were also no significant changes in transcriptomic or metabolomic responses in lung or BEAS-2B cells to suggest adverse effects.

Original languageEnglish
Article number556
Pages (from-to)1-24
Number of pages24
JournalInternational Journal of Molecular Sciences
Issue number2
Publication statusPublished - 2 Jan 2021

Bibliographical note

Funding Information:
Funding: 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.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Inhalation
  • Iron oxide
  • Lung
  • Nanoparticle
  • Omics
  • Rat
  • Ultrafine
  • ultrafine
  • rat
  • nanoparticle
  • lung
  • iron oxide
  • inhalation
  • omics


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