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

Author:

Andrews Jack P. M.,Joshi Shruti S.ORCID,Tzolos Evangelos,Syed Maaz B.,Cuthbert Hayley,Crica Livia E.ORCID,Lozano NeusORCID,Okwelogu Emmanuel,Raftis Jennifer B.,Bruce Lorraine,Poland Craig A.ORCID,Duffin RodgerORCID,Fokkens Paul H. B.,Boere A. John F.,Leseman Daan L. A. C.,Megson Ian L.ORCID,Whitfield Phil D.,Ziegler Kerstin,Tammireddy Seshu,Hadjidemetriou Marilena,Bussy CyrillORCID,Cassee Flemming R.,Newby David E.ORCID,Kostarelos KostasORCID,Miller Mark R.ORCID

Abstract

AbstractGraphene oxide nanomaterials are being developed for wide-ranging applications but are associated with potential safety concerns for human health. We conducted a double-blind randomized controlled study to determine how the inhalation of graphene oxide nanosheets affects acute pulmonary and cardiovascular function. Small and ultrasmall graphene oxide nanosheets at a concentration of 200 μg m3 or filtered air were inhaled for 2 h by 14 young healthy volunteers in repeated visits. Overall, graphene oxide nanosheet exposure was well tolerated with no adverse effects. Heart rate, blood pressure, lung function and inflammatory markers were unaffected irrespective of graphene oxide particle size. Highly enriched blood proteomics analysis revealed very few differential plasma proteins and thrombus formation was mildly increased in an ex vivo model of arterial injury. Overall, acute inhalation of highly purified and thin nanometre-sized graphene oxide nanosheets was not associated with overt detrimental effects in healthy humans. These findings demonstrate the feasibility of carefully controlled human exposures at a clinical setting for risk assessment of graphene oxide, and lay the foundations for investigating the effects of other two-dimensional nanomaterials in humans. Clinicaltrials.gov ref: NCT03659864.

Funder

British Heart Foundation

Publisher

Springer Science and Business Media LLC

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