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Inhaled carbon nanotubes reach the subpleural tissue in mice

Nature Nanotechnology volume 4, pages 747–751 (2009)Cite this article

Abstract

Carbon nanotubes are shaped like fibres1 and can stimulate inflammation at the surface of the peritoneum when injected into the abdominal cavity of mice2, raising concerns that inhaled nanotubes3 may cause pleural fibrosis and/or mesothelioma4. Here, we show that multiwalled carbon nanotubes reach the subpleura in mice after a single inhalation exposure of 30 mg m−3 for 6 h. Nanotubes were embedded in the subpleural wall and within subpleural macrophages. Mononuclear cell aggregates on the pleural surface increased in number and size after 1 day and nanotube-containing macrophages were observed within these foci. Subpleural fibrosis unique to this form of nanotubes increased after 2 and 6 weeks following inhalation. None of these effects was seen in mice that inhaled carbon black nanoparticles or a lower dose of nanotubes (1 mg m−3). This work suggests that minimizing inhalation of nanotubes during handling is prudent until further long-term assessments are conducted.

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Figure 1: Aerosolization of carbon nanotubes.
Figure 2: Inhaled carbon nanotubes reach the subpleura in mice.
Figure 3: Pleural immune response after carbon nanotube inhalation in mice.
Figure 4: Subpleural fibrosis in mice after carbon nanotube inhalation.

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Acknowledgements

This study was funded by the American Chemistry Council's Long Range Research Initiative provided to The Hamner Institutes for Health Sciences, The National Institutes of Environmental Health Sciences grant no. R21-ES015801-01, North Carolina State University College of Agricultural and Life Sciences, and the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. ACS/LRRI provided funds only and played no role in study design, data gathering and interpretation, authoring of the manuscript, or decision to publish. Special thanks go to Betsy Gross-Bermudez and the pathology staff at The Hamner Institutes for excellent technical assistance, and to A. Taylor at NCSU for critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Environmental and Molecular Toxicology, College of Agricultural and Life Sciences, North Carolina State University, Raleigh, 27695, North Carolina, USA

    Jessica P. Ryman-Rasmussen, Mark F. Cesta & James C. Bonner

  2. The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina, 27709, USA

    Jessica P. Ryman-Rasmussen, Mark F. Cesta, Earl W. Tewksbury, Owen R. Moss, Brian A. Wong, Darol E. Dodd & Melvin E. Andersen

  3. Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA

    Mark F. Cesta

  4. Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, 27695, North Carolina, USA

    Arnold R. Brody

  5. Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, 27695, North Carolina, USA

    Jeanette K. Shipley-Phillips & Jeffrey I. Everitt

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  1. Jessica P. Ryman-Rasmussen
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Contributions

J.P.R. and J.C.B. initiated, directed and performed all experiments and took responsibility for planning and writing the manuscript. J.P.R., M.E.A., B.A.W., O.M. and J.C.B designed the inhalation exposure experiment. B.W. and E.W.T. designed the inhalation exposure apparatus and performed testing for dosimetery. M.F.C., A.R.B., J.E. and J.C.B. evaluated pathology for identification and verification of pleural lesion identity. J.K.S. performed electron microscopy for identification of nanotubes in lung tissue. A.R.B. and M.E.A. provided intellectual support on mesothelioma and risk assessement.

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Correspondence to James C. Bonner.

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Ryman-Rasmussen, J., Cesta, M., Brody, A. et al. Inhaled carbon nanotubes reach the subpleural tissue in mice. Nature Nanotech 4, 747–751 (2009). https://doi.org/10.1038/nnano.2009.305

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