Open Access Research

Factoring-in agglomeration of carbon nanotubes and nanofibers for better prediction of their toxicity versus asbestos

Ashley R Murray12, Elena R Kisin1, Alexey V Tkach1, Naveena Yanamala34, Robert Mercer1, Shih-Houng Young1, Bengt Fadeel5, Valerian E Kagan3 and Anna A Shvedova126*

  • * Corresponding author: Anna A Shvedova

  • † Equal contributors

Author Affiliations

1 Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA

2 Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV, USA

3 Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA

4 Department of Structural Biology, University of Pittsburgh, Pittsburgh, PA, USA

5 Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

6 Health Effects Laboratory Division, Pathology and Physiology Research Branch, NIOSH, M/L 2015, 1095 Willowdale Road, Morgantown, WV 26505, USA

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Particle and Fibre Toxicology 2012, 9:10  doi:10.1186/1743-8977-9-10

Published: 10 April 2012



Carbon nanotubes (CNT) and carbon nanofibers (CNF) are allotropes of carbon featuring fibrous morphology. The dimensions and high aspect ratio of CNT and CNF have prompted the comparison with naturally occurring asbestos fibers which are known to be extremely pathogenic. While the toxicity and hazardous outcomes elicited by airborne exposure to single-walled CNT or asbestos have been widely reported, very limited data are currently available describing adverse effects of respirable CNF.


Here, we assessed pulmonary inflammation, fibrosis, oxidative stress markers and systemic immune responses to respirable CNF in comparison to single-walled CNT (SWCNT) and asbestos. Pulmonary inflammatory and fibrogenic responses to CNF, SWCNT and asbestos varied depending upon the agglomeration state of the particles/fibers. Foci of granulomatous lesions and collagen deposition were associated with dense particle-like SWCNT agglomerates, while no granuloma formation was found following exposure to fiber-like CNF or asbestos. The average thickness of the alveolar connective tissue - a marker of interstitial fibrosis - was increased 28 days post SWCNT, CNF or asbestos exposure. Exposure to SWCNT, CNF or asbestos resulted in oxidative stress evidenced by accumulations of 4-HNE and carbonylated proteins in the lung tissues. Additionally, local inflammatory and fibrogenic responses were accompanied by modified systemic immunity, as documented by decreased proliferation of splenic T cells ex vivo on day 28 post exposure. The accuracies of assessments of effective surface area for asbestos, SWCNT and CNF (based on geometrical analysis of their agglomeration) versus estimates of mass dose and number of particles were compared as predictors of toxicological outcomes.


We provide evidence that effective surface area along with mass dose rather than specific surface area or particle number are significantly correlated with toxicological responses to carbonaceous fibrous nanoparticles. Therefore, they could be useful dose metrics for risk assessment and management.