First-in-human controlled inhalation of thin graphene oxide nanosheets to study acute cardiorespiratory responses

Jack Andrews, Shruti Joshi, Evangelos Tzolos, Maaz Syed, Hayley Cuthbert, Livia Crica, Neus Lozano, Jennifer Raftis, Lorraine Bruce, Craig Poland, Rodger Duffin, Paul Fokkens, Daan Leseman, John Boere, Ian Megson, Phillip Whitfield, Emmanuel Okwelogu, Marilena Hadjidemetriou, Cyrill Bussy, Flemming CasseeDavid Newby, Kostas Kostarelos, Mark Miller

Research output: Contribution to journalArticlepeer-review

Abstract

Graphene oxide nanomaterials have been developed for wide-ranging applications, but has potential safety concerns for human health. Controlled inhalation exposures in human volunteers have been a vital means to determine the effects and mechanisms of ultrafine particles in air pollution, however, few studies have used this approach to explore the effects of nanomaterials. We conducted a double-blind randomised controlled study to determine whether inhalation of graphene oxide affects pulmonary or cardiovascular function. A high purity graphene oxide was synthesised with a thickness of 1-2 layers in two sizes: ‘small’ (lateral dimensions: 100-1700 nm) and ‘ultrasmall’ (30-500 nm). Graphene oxide particles at 200 µg/m3, or filtered air, were inhaled for 2 hours by 14 young healthy volunteers on repeated visits, with measurement of cardiorespiratory parameters before and across 4 hours after exposure. Graphene oxide exposure was well-tolerated with no adverse effects. Heart rate, blood pressure, lung function and inflammatory markers were unaffected by graphene oxide irrespective of particle size. GO did not change blood biomarkers of coagulation, however, there was a mild increase in thrombus formation in an ex vivo model of arterial injury. Proteomics revealed very few differential plasma proteins. Overall, acute inhalation of graphene oxide was not associated with overt detrimental effects in healthy humans. These findings demonstrate the feasibility of carefully controlled human exposures for risk assessment of graphene nanomaterials.
Original languageEnglish
JournalNature Nanotechnology
DOIs
Publication statusPublished - 16 Feb 2024

Keywords

  • graphene oxide
  • lung
  • heart
  • toxicity
  • exposure
  • workplace

Research Beacons, Institutes and Platforms

  • Advanced materials
  • National Graphene Institute
  • Henry Royce Institute
  • Thomas Ashton Institute
  • Lydia Becker Institute

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  • CDT in Science and Applications of Graphene and Related Nanomaterial

    Grigorieva, I. (PI), Burnett, H. (PGR student), Cusworth, E. (PGR student), Deaconu, D.-A. (PGR student), Dumitriu-Iovanescu, A.-D. (PGR student), Kang, Y.-W. (PGR student), Little, J. (PGR student), Rees, E. (PGR student), Selles, F. (PGR student), Shaker, M. (PGR student), Soong, Y.-C. (PGR student), Swindell, J. (PGR student), Tainton, G. (PGR student), Wood, H. (PGR student), Astles, T. (PGR student), Carl, A. (PGR student), Chen, G. (PGR student), Richard De Latour, H. (PGR student), Dowinton, O. (PGR student), Haskell, S. (PGR student), Hills, K. (PGR student), Hoole, C. (PGR student), Huang, Y. (PGR student), Kalsi, T. (PGR student), Powell, L. (PGR student), Quiligotti, K. (PGR student), Rimmer, J. (PGR student), Smith, L. (PGR student), Thornley, W. (PGR student), Yang, J. (PGR student), Young, W. (PGR student), Zhao, M. (PGR student), Al Busaidi, R. (PGR student), Al Ruqeishi, E. (PGR student), Chadha, A. (PGR student), Chen, M. (PGR student), Dennis, G. (PGR student), Dunn, E. (PGR student), Gamblen, E. (PGR student), Gao, Y. (PGR student), Georgantas, Y. (PGR student), Jiang, Z. (PGR student), Karakasidi, A. (PGR student), Mcellistrim, A. (PGR student), Meehan, M. (PGR student), Okwelogu, E. (PGR student), Taylor, M. (PGR student), Wang, W. (PGR student), Xin, B. (PGR student), Castle, C. (PGR student), Clout, P. (PGR student), Dean, S. D. (PGR student), Fordham, A. (PGR student), Griffin, E. (PGR student), Hardwick, T. (PGR student), Hawkins-Pottier, G. (PGR student), Jones, A. (PGR student), Lewthwaite, K. (PGR student), Monteil, S. (PGR student), Moulsdale, C. (PGR student), Mullan, C. (PGR student), Orts Mercadillo, V. (PGR student), Sanderson, D. (PGR student), Skliueva, I. (PGR student), Skuse, C. (PGR student), Steiner, P. (PGR student), Winstanley, B. (PGR student), Barry, D. (PGR student), Brooks, D. (PGR student), Cai, J. (PGR student), Chen, Y. (PGR student), Chen, C. (PGR student), Draude, A. (PGR student), Emmerson, C. (PGR student), Gavriliuc, V. (PGR student), Greaves, M. (PGR student), Higgins, E. (PGR student), Mcmaster, R. (PGR student), Mcnair, R. (PGR student), O'Brien, C. (PGR student), Peasey, A. (PGR student), Pinter, G. (PGR student), Shao, S. (PGR student), Thomas, D. (PGR student), Thomas, D. (PGR student), Tsim, L. T. B. (PGR student), Wengraf, J. (PGR student), Weston, A. (PGR student), Yu, T. (PGR student), De Libero, H. (PGR student), Chan, K. C. (PGR student), Tan, Y. T. (PGR student) & Thomson, T. (CoI)

    1/04/1431/10/25

    Project: Other

  • Safety Assessment of Graphene‐Based Materials

    Fadeel, B., Baker, J., Ballerini, L., Bussy, C., Candotto Carniel, F., Tretiach, M., Pelin, M., Buerki‐Thurnherr, T., Kanerva, T., Navas, J. M., Vázquez, E., Rodriguez Unamuno, V., Lehtonen, P., González, M., Rauscher, H., Riego Sintes, J., Kostarelos, K., Bianco, A. & Prato, M., 15 Jan 2025, (E-pub ahead of print) In: Small. e2404570.

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