Pulmonary toxicity of two different multi-walled carbon nanotubes in rat: Comparison between intratracheal instillation and inhalation exposure

Laurent Gaté*, Kristina Bram Knudsen, Carole Seidel, Trine Berthing, Laëtitia Chézeau, Nicklas Raun Jacobsen, Sarah Valentino, Håkan Wallin, Sébastien Bau, Henrik Wolff, Sylvie Sébillaud, Mylène Lorcin, Stéphane Grossmann, Stéphane Viton, Hervé Nunge, Christian Darne, Ulla Birgitte Vogel, Frédéric Cosnier

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Multi-walled carbon nanotubes (MWCNTs), which vary in length, diameter, functionalization and specific surface area, are used in diverse industrial processes. Since these nanomaterials have a high aspect ratio and are biopersistant in the lung, there is a need for a rapid identification of their potential health hazard. We assessed in Sprague-Dawley rats the pulmonary toxicity of two pristine MWCNTs (the "long and thick" NM-401 and the "short and thin" NM-403) following either intratracheal instillation or 4-week inhalation in order to gain insights into the predictability and intercomparability of the two methods. The deposited doses following inhalation were lower than the instilled doses. Both types of carbon nanotube induced pulmonary neutrophil influx using both exposure methods. This influx correlated with deposited surface area across MWCNT types and means of exposure at two different time points, 1-3 days and 28-30 days post-exposure. Increased levels of DNA damage were observed across doses and time points for both exposure methods, but no dose-response relationship was observed. Intratracheal instillation of NM-401 induced fibrosis at the highest dose while lower lung deposited doses obtained by inhalation did not induce such lung pathology. No fibrosis was observed following NM-403 exposure. When the deposited dose was taken into account, sub-acute inhalation and a single instillation of NM-401 and NM-403 produced very similar inflammation and DNA damage responses. Our data suggest that the dose-dependent inflammatory responses observed after intratracheal instillation and inhalation of MWCNTs are similar and were predicted by the deposited surface area.
Original languageEnglish
JournalTOXICOLOGY AND APPLIED PHARMACOLOGY
Volume375
Pages (from-to)17-31
ISSN0041-008X
DOIs
Publication statusPublished - 2019

Keywords

  • Carbon nanotubes
  • Inhalation
  • Intratracheal instillation
  • Lung inflammation
  • Rat

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