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Related Experiment Videos

Laurent Gaté1, Kristina Bram Knudsen2, Carole Seidel1

  • 1Institut National de Recherche et de Sécurité, F-54519 Vandoeuvre-lès-Nancy Cedex, France.

Toxicology and Applied Pharmacology
|May 11, 2019
PubMed
Summary

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Pulmonary toxicity from multi-walled carbon nanotubes (MWCNTs) in rats showed similar inflammation and DNA damage for both intratracheal instillation and inhalation exposure. Deposited surface area predicted dose-dependent inflammatory responses.

Area of Science:

  • Nanotoxicology
  • Pulmonary Toxicology
  • Materials Science

Background:

  • Multi-walled carbon nanotubes (MWCNTs) are industrially relevant due to their unique properties.
  • Their high aspect ratio and biopersistence in the lung necessitate rapid health hazard identification.
  • Variations in MWCNT characteristics (length, diameter, surface area) influence their toxicological profile.

Purpose of the Study:

  • To compare pulmonary toxicity of two MWCNTs (NM-401 and NM-403) via intratracheal instillation and inhalation in Sprague-Dawley rats.
  • To assess the predictability and intercomparability of these two exposure methods.
  • To investigate the relationship between deposited dose, surface area, and observed toxicological endpoints.

Main Methods:

  • Two pristine MWCNTs (NM-401: long/thick, NM-403: short/thin) were administered to rats via intratracheal instillation or 4-week inhalation.
Keywords:
Carbon nanotubesInhalationIntratracheal instillationLung inflammationRat

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  • Pulmonary toxicity was assessed by measuring neutrophil influx, DNA damage, and fibrosis at 1-3 days and 28-30 days post-exposure.
  • Deposited doses were quantified to enable comparison between exposure routes.
  • Main Results:

    • Both MWCNT types induced pulmonary neutrophil influx and DNA damage via both exposure routes.
    • Inflammatory response correlated with deposited surface area across MWCNT types and exposure methods.
    • Fibrosis was observed only with NM-401 at the highest instilled dose, not with inhalation or NM-403.

    Conclusions:

    • Intratracheal instillation and sub-acute inhalation of MWCNTs produce similar dose-dependent inflammatory and DNA damage responses when deposited dose is considered.
    • Deposited surface area is a key factor in predicting MWCNT-induced pulmonary inflammation.
    • The study highlights the importance of considering deposited dose for intercomparing toxicity data from different exposure routes.