Subchronic Inhalation Toxicity Study with a Vapor-Grown Carbon Nanofiber in Male and Female Rats (OECD 413): Does Nanofiber Exposure Have Adverse Impacts on the Cardiovascular System?

Part of the Current Topics in Environmental Health and Preventive Medicine book series (CTEHPM)


The objective of this 90-day inhalation toxicity study in male/female rats exposed to vapor-grown carbon nanofibers (CNF) was to assess both the lung toxicity and systemic (cardiovascular) effects following exposures to 0, 0.54, 2.5, or 25 mg/m3. From a respiratory tract standpoint, there was some minor histopathological, cell proliferative, and inflammatory effects at the highest concentration—25 mg/m3. In addition, there was some evidence that aerosol exposures at the highest concentration (25 mg/m3) resulted in a minimal translocation of the inhaled nanofibers from the respiratory tract to systemic extrapulmonary sites in the body. This finding led to the hypothesis that the movement of inhaled fibers into the systemic bloodstream could facilitate a cross-talk relationship between the respiratory tract and cardiovascular effects, thus impacting blood coagulation effects. Accordingly, common cardiovascular/coagulation indices were measured—including cardiomyocyte proliferation parameters; systemic inflammation indices—such as C-reactive protein and four different coagulation parameters: (1) fibrinogen levels; (2) platelet counts; (3) PT; and (4) aPTT bleeding times. The results demonstrated no significant differences were measured between air and high dose, CNF-exposed rats. It was concluded that no apparent cross-talk was demonstrated between local respiratory and systemic/cardiovascular endpoints. Based upon the data generated in this 90-day, subchronic inhalation study, it seems likely that the pulmonary toxicity endpoints of this study would be useful in accurately predicting lung inflammatory outcomes in a shorter-term inhalation study. However, the pulmonary histopathology and cardiovascular endpoints described in this study likely require the subchronic inhalation testing exposure protocol.


Carbon nanofiber inhalation exposure Translocation of inhaled fibers Cardiovascular effects Pulmonary effects Coagulation factors C-reactive protein 



The following individuals made significant technical contributions to the conduct and implementation of this study: Dr. Michael DeLorme, Ken Reed, John Nogaj, Bill Ellis, Morgan Golt, David Grinstead, Elizabeth Wilkinson, Lisa Lewis, Carolyn Lloyd, Steve Records, Don Hildabrant, Antidio Lorenzo, Jeff Holt, Melissa Fallers, and Tracey White. Dr. Shekhar Subramoney the TEM micrograph.

Funding: This work was supported by Showa Denko, KK.


  1. 1.
    Ma-Hock L, Treumann S, Strauss V, Brill S, Luizi F, Mertler M, Wiench K, Gamer AO, van Ravenzwaay B, Landsiedel R. Inhalation toxicity of multiwall carbon nanotubes in rats exposed for 3 months. Toxicol Sci. 2009;112:468–81.CrossRefGoogle Scholar
  2. 2.
    Pauluhn J. Subchronic 13-week inhalation exposure of rats to multiwalled carbon nanotubes: toxic effects are determined by density of agglomerate structures, not fibrillar structures. Toxicol Sci. 2010;113:226–42.CrossRefGoogle Scholar
  3. 3.
    Morimoto Y, Hirohashi M, Ogami A, Oyabu T, Myojo T, Todoroki M, Yamamoto M, Hashiba M, Mizuguchi Y, Lee BW, Kuroda E, Shimada M, Wang WN, Yamamoto K, Fujita K, Endoh S, Uchida K, Kobayashi N, Mizuno K, Inada M, Tao H, Nakazato T, Nakanishi J, Tanaka I. Pulmonary toxicity of well-dispersed multi-wall carbon nanotubes following inhalation and intratracheal instillation. Nanotoxicology. 2012;6:587–99.CrossRefGoogle Scholar
  4. 4.
    DeLorme MP, Muro Y, Arai T, Banas DA, Frame SR, Reed KL, Warheit DB. Ninety-day inhalation toxicity study with a vapor grown carbon nanofiber in rats. Toxicol Sci. 2012;128(2):449–60.CrossRefGoogle Scholar
  5. 5.
    Warheit DB, DeLorme MP. CNT biopersistence and the fibre paradigm. In: Donaldson K, Poland C, Duffin R, Bonner J, editors. The toxicology of carbon nanotubes. New York: Cambridge University Press; 2012.Google Scholar

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Warheit Scientific LLCWilmingtonUSA

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