Long-term retention of pristine multi-walled carbon nanotubes in rat lungs after intratracheal instillation

J Appl Toxicol. 2016 Apr;36(4):501-9. doi: 10.1002/jat.3271. Epub 2015 Dec 29.

Abstract

As a result of the growing potential industrial and medical applications of multi-walled carbon nanotubes (MWCNTs), people working in or residing near facilities that manufacture them may be exposed to airborne MWCNTs in the future. Because of concerns regarding their toxicity, quantitative data on the long-term clearance of pristine MWCNTs from the lungs are required. We administered pristine MWCNTs well dispersed in 0.5 mg ml(-1) Triton-X solution to rats at doses of 0.20 or 0.55 mg via intratracheal instillation and investigated clearance over a 12-month observation period. The pristine MWCNTs pulmonary burden was determined 1, 3, 7, 28, 91, 175 and 364 days after instillation using a method involving combustive oxidation and infrared analysis, combined with acid digestion and heat pretreatment. As 0.15- and 0.38-mg MWCNTs were detected 1 day after administration of 0.20 and 0.55 mg MWCNTs, respectively, approximately 30% of administrated MWCNTs may have been cleared by bronchial ciliary motion within 24 h of administration. After that, the pulmonary MWCNT burden did not decrease significantly over time for up to 364 days after instillation, suggesting that MWCNTs were not readily cleared from the lung. Transmission electron microscopy (TEM) showed that alveolar macrophages internalized the MWCNTs and retained in the lung for at least 364 days after instillation. MWCNTs were not detected in the liver or brain within the 364-day study period (<0.04 mg per liver, < 0.006 mg per brain).

Keywords: intratracheal instillation; multi-walled carbon nanotube; nanomaterial; pulmonary clearance; toxicokinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Animals
  • Brain / metabolism
  • Dose-Response Relationship, Drug
  • Limit of Detection
  • Liver / metabolism
  • Lung / metabolism*
  • Macrophages, Alveolar / metabolism
  • Male
  • Microscopy, Electron, Transmission
  • Nanotubes, Carbon / chemistry*
  • Rats
  • Rats, Wistar

Substances

  • Nanotubes, Carbon