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

Cite this

Gaté, Laurent ; Knudsen, Kristina Bram ; Seidel, Carole ; Berthing, Trine ; Chézeau, Laëtitia ; Jacobsen, Nicklas Raun ; Valentino, Sarah ; Wallin, Håkan ; Bau, Sébastien ; Wolff, Henrik ; Sébillaud, Sylvie ; Lorcin, Mylène ; Grossmann, Stéphane ; Viton, Stéphane ; Nunge, Hervé ; Darne, Christian ; Vogel, Ulla Birgitte ; Cosnier, Frédéric. / Pulmonary toxicity of two different multi-walled carbon nanotubes in rat: Comparison between intratracheal instillation and inhalation exposure. In: TOXICOLOGY AND APPLIED PHARMACOLOGY. 2019 ; Vol. 375. pp. 17-31.
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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.",
keywords = "Carbon nanotubes, Inhalation, Intratracheal instillation, Lung inflammation, Rat",
author = "Laurent Gat{\'e} and Knudsen, {Kristina Bram} and Carole Seidel and Trine Berthing and La{\"e}titia Ch{\'e}zeau and Jacobsen, {Nicklas Raun} and Sarah Valentino and H{\aa}kan Wallin and S{\'e}bastien Bau and Henrik Wolff and Sylvie S{\'e}billaud and Myl{\`e}ne Lorcin and St{\'e}phane Grossmann and St{\'e}phane Viton and Herv{\'e} Nunge and Christian Darne and Vogel, {Ulla Birgitte} and Fr{\'e}d{\'e}ric Cosnier",
year = "2019",
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language = "English",
volume = "375",
pages = "17--31",
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Gaté, L, Knudsen, KB, Seidel, C, Berthing, T, Chézeau, L, Jacobsen, NR, Valentino, S, Wallin, H, Bau, S, Wolff, H, Sébillaud, S, Lorcin, M, Grossmann, S, Viton, S, Nunge, H, Darne, C, Vogel, UB & Cosnier, F 2019, 'Pulmonary toxicity of two different multi-walled carbon nanotubes in rat: Comparison between intratracheal instillation and inhalation exposure', TOXICOLOGY AND APPLIED PHARMACOLOGY, vol. 375, pp. 17-31. https://doi.org/10.1016/j.taap.2019.05.001

Pulmonary toxicity of two different multi-walled carbon nanotubes in rat: Comparison between intratracheal instillation and inhalation exposure. / Gaté, Laurent; Knudsen, Kristina Bram; Seidel, Carole; Berthing, Trine; Chézeau, Laëtitia; Jacobsen, Nicklas Raun; Valentino, Sarah; Wallin, Håkan; Bau, Sébastien; Wolff, Henrik; Sébillaud, Sylvie; Lorcin, Mylène; Grossmann, Stéphane; Viton, Stéphane; Nunge, Hervé; Darne, Christian; Vogel, Ulla Birgitte; Cosnier, Frédéric.

In: TOXICOLOGY AND APPLIED PHARMACOLOGY, Vol. 375, 2019, p. 17-31.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Pulmonary toxicity of two different multi-walled carbon nanotubes in rat: Comparison between intratracheal instillation and inhalation exposure

AU - Gaté, Laurent

AU - Knudsen, Kristina Bram

AU - Seidel, Carole

AU - Berthing, Trine

AU - Chézeau, Laëtitia

AU - Jacobsen, Nicklas Raun

AU - Valentino, Sarah

AU - Wallin, Håkan

AU - Bau, Sébastien

AU - Wolff, Henrik

AU - Sébillaud, Sylvie

AU - Lorcin, Mylène

AU - Grossmann, Stéphane

AU - Viton, Stéphane

AU - Nunge, Hervé

AU - Darne, Christian

AU - Vogel, Ulla Birgitte

AU - Cosnier, Frédéric

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Carbon nanotubes

KW - Inhalation

KW - Intratracheal instillation

KW - Lung inflammation

KW - Rat

U2 - 10.1016/j.taap.2019.05.001

DO - 10.1016/j.taap.2019.05.001

M3 - Journal article

VL - 375

SP - 17

EP - 31

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

ER -