Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide

PLoS One. 2017 Jun 1;12(6):e0178355. doi: 10.1371/journal.pone.0178355. eCollection 2017.

Abstract

We investigated toxicity of 2-3 layered >1 μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we assessed exposure levels of particulate matter emitted during production of graphene in a clean room and in a normal industrial environment using chemical vapour deposition. Toxicity was evaluated at day 1, 3, 28 and 90 days (18, 54 and 162 μg/mouse), except for GO exposed mice at day 28 and 90 where only the lowest dose was evaluated. GO induced a strong acute inflammatory response together with a pulmonary (Serum-Amyloid A, Saa3) and hepatic (Saa1) acute phase response. rGO induced less acute, but a constant and prolonged inflammation up to day 90. Lung histopathology showed particle agglomerates at day 90 without signs of fibrosis. In addition, DNA damage in BAL cells was observed across time points and doses for both GO and rGO. In conclusion, pulmonary exposure to GO and rGO induced inflammation, acute phase response and genotoxicity but no fibrosis.

MeSH terms

  • Acute-Phase Reaction*
  • Animals
  • Bronchoalveolar Lavage Fluid
  • Female
  • Graphite / chemistry
  • Graphite / toxicity*
  • Inflammation / pathology*
  • Lung / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Mutagens / toxicity*
  • Oxidation-Reduction
  • Oxides / chemistry

Substances

  • Mutagens
  • Oxides
  • Graphite

Grants and funding

The work leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n° FP7-604000. The funder provided support in the form of salaries for authors [BA, AP, AZ], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.