Organ accumulation and carcinogenicity of highly dispersed multi-walled carbon nanotubes administered intravenously in transgenic rasH2 mice

Int J Nanomedicine. 2019 Aug 12:14:6465-6480. doi: 10.2147/IJN.S208129. eCollection 2019.

Abstract

Purpose: Multiwalled carbon nanotubes (MWCNTs) have been known to enter the circulatory system via the lungs from inhalation exposure; however, its carcinogenicity and subsequent accumulation in other organs have not been adequately reported in the literature. Moreover, the safety of MWCNTs as a biomaterial has remained a matter of debate, particularly when the material enters the circulatory system. To address these problems, we used carcinogenic rasH2 transgenic mice to intravenously administer highly dispersed MWCNTs and to evaluate their carcinogenicity and accumulation in the organs.

Methods: Two types of MWCNTs (thin- and thick-MWCNTs) were intravenously administered at a high dose (approximately 0.7 mg per kg body weight) and low dose (approximately 0.07 mg per kg body weight).

Results: MWCNTs showed pancreatic accumulation in 3.2% of mice administered with MWCNTs, but there was no accumulation in other organs. In addition, there was no significant difference in the incidence of tumor among the four MWCNTs-administered groups compared to the vehicle group without MWCNTs administration. Blood tests revealed elevated levels in mean red blood cell volume and mean red blood cell hemoglobin level for the MWCNTs-administered group, in addition to an increase in eotaxin.

Conclusion: The present study demonstrated that the use of current technology to sufficiently disperse MWCNTs resulted in minimal organ accumulation with no evidence of carcinogenicity.

Keywords: carcinogenicity; dispersion; multiwalled carbon nanotubes; organ accumulation; rasH2 transgenic mouse.

MeSH terms

  • Administration, Intravenous
  • Animals
  • Body Weight
  • Carcinogenesis / pathology
  • Carcinogens / toxicity*
  • Cytokines / metabolism
  • Lung / drug effects
  • Lung / pathology
  • Male
  • Mice, Transgenic
  • Nanotubes, Carbon / toxicity*
  • Nanotubes, Carbon / ultrastructure
  • Survival Analysis
  • Tissue Distribution / drug effects

Substances

  • Carcinogens
  • Cytokines
  • Nanotubes, Carbon