Pulmonary Toxicity of Long, Thick MWCNT and Very Long, Thin Carboxylated MWCNT Aerosols Following 28 Days Whole-Body Exposure

Pulmonary exposure to carbon nanotubes (CNTs) has been linked to a series of adverse respiratory effects in animal models, including inflammation, genotoxicity, fibrosis, and granuloma formation, the degree and characteristics of which are considered dependent upon the detailed physicochemical prope...

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Main Authors: Chang Guo, Matthew D. Wright, Alison Buckley, Adam Laycock, Trine Berthing, Ulla Vogel, Frédéric Cosnier, Laurent Gaté, Martin O. Leonard, Rachel Smith
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Toxics
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Online Access:https://www.mdpi.com/2305-6304/13/5/401
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author Chang Guo
Matthew D. Wright
Alison Buckley
Adam Laycock
Trine Berthing
Ulla Vogel
Frédéric Cosnier
Laurent Gaté
Martin O. Leonard
Rachel Smith
author_facet Chang Guo
Matthew D. Wright
Alison Buckley
Adam Laycock
Trine Berthing
Ulla Vogel
Frédéric Cosnier
Laurent Gaté
Martin O. Leonard
Rachel Smith
author_sort Chang Guo
collection DOAJ
description Pulmonary exposure to carbon nanotubes (CNTs) has been linked to a series of adverse respiratory effects in animal models, including inflammation, genotoxicity, fibrosis, and granuloma formation, the degree and characteristics of which are considered dependent upon the detailed physicochemical properties of the material as inhaled. To further explore the effect of variations in physicochemical properties on pulmonary effects, two different multi-walled CNTs (MWCNTs) were tested in vivo: a pristine MWCNT (pMWCNT) (NM-401) and a surface-modified MWCNT (MWCNT-COOH). Female Sprague–Dawley rats were whole-body exposed for 28 days to MWCNT aerosols (pMWCNT (0.5 and 1.5 mg/m<sup>3</sup>) and MWCNT-COOH (1.5 and 4.5 mg/m<sup>3</sup>)) and followed up to 1 year post-exposure. The inhalation exposures resulted in relatively low estimated lung deposition. Bronchoalveolar lavage fluid (BALF) analysis indicated inflammation levels broadly consistent with deposited dose levels. Lung histopathology indicated that both MWCNTs produced very limited toxicological effects; however, global mRNA expression levels in lung tissue and BALF cytokines indicated different characteristics for the two MWCNTs. For example, pMWCNT but not MWCNT-COOH exposure induced osteopontin production, suggestive of potential pre-fibrosis/fibrosis effects linked to the higher aspect ratio aerosol particles. This is of concern as brightfield and enhanced darkfield microscopy indicated the persistence of pMWCNT fibres in lung tissue.
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spelling doaj-art-16049a4fcbad4b058ff5402084d2f1b32025-08-20T02:33:51ZengMDPI AGToxics2305-63042025-05-0113540110.3390/toxics13050401Pulmonary Toxicity of Long, Thick MWCNT and Very Long, Thin Carboxylated MWCNT Aerosols Following 28 Days Whole-Body ExposureChang Guo0Matthew D. Wright1Alison Buckley2Adam Laycock3Trine Berthing4Ulla Vogel5Frédéric Cosnier6Laurent Gaté7Martin O. Leonard8Rachel Smith9Toxicology Department, UK Health Security Agency, Harwell Campus, Didcot OX11 0RQ, UKToxicology Department, UK Health Security Agency, Harwell Campus, Didcot OX11 0RQ, UKToxicology Department, UK Health Security Agency, Harwell Campus, Didcot OX11 0RQ, UKToxicology Department, UK Health Security Agency, Harwell Campus, Didcot OX11 0RQ, UKNational Research Centre for the Working Environment, DK-2100 Copenhagen, DenmarkNational Research Centre for the Working Environment, DK-2100 Copenhagen, DenmarkFrench Research and Safety Institute for the Prevention of Occupational Accidents and Diseases (INRS), Toxicology and Biomonitoring Division, 54519 Vandoeuvre les Nancy, FranceFrench Research and Safety Institute for the Prevention of Occupational Accidents and Diseases (INRS), Toxicology and Biomonitoring Division, 54519 Vandoeuvre les Nancy, FranceToxicology Department, UK Health Security Agency, Harwell Campus, Didcot OX11 0RQ, UKToxicology Department, UK Health Security Agency, Harwell Campus, Didcot OX11 0RQ, UKPulmonary exposure to carbon nanotubes (CNTs) has been linked to a series of adverse respiratory effects in animal models, including inflammation, genotoxicity, fibrosis, and granuloma formation, the degree and characteristics of which are considered dependent upon the detailed physicochemical properties of the material as inhaled. To further explore the effect of variations in physicochemical properties on pulmonary effects, two different multi-walled CNTs (MWCNTs) were tested in vivo: a pristine MWCNT (pMWCNT) (NM-401) and a surface-modified MWCNT (MWCNT-COOH). Female Sprague–Dawley rats were whole-body exposed for 28 days to MWCNT aerosols (pMWCNT (0.5 and 1.5 mg/m<sup>3</sup>) and MWCNT-COOH (1.5 and 4.5 mg/m<sup>3</sup>)) and followed up to 1 year post-exposure. The inhalation exposures resulted in relatively low estimated lung deposition. Bronchoalveolar lavage fluid (BALF) analysis indicated inflammation levels broadly consistent with deposited dose levels. Lung histopathology indicated that both MWCNTs produced very limited toxicological effects; however, global mRNA expression levels in lung tissue and BALF cytokines indicated different characteristics for the two MWCNTs. For example, pMWCNT but not MWCNT-COOH exposure induced osteopontin production, suggestive of potential pre-fibrosis/fibrosis effects linked to the higher aspect ratio aerosol particles. This is of concern as brightfield and enhanced darkfield microscopy indicated the persistence of pMWCNT fibres in lung tissue.https://www.mdpi.com/2305-6304/13/5/401nanotoxicologycarbon nanotubesCNTMWCNTNM-401rat
spellingShingle Chang Guo
Matthew D. Wright
Alison Buckley
Adam Laycock
Trine Berthing
Ulla Vogel
Frédéric Cosnier
Laurent Gaté
Martin O. Leonard
Rachel Smith
Pulmonary Toxicity of Long, Thick MWCNT and Very Long, Thin Carboxylated MWCNT Aerosols Following 28 Days Whole-Body Exposure
Toxics
nanotoxicology
carbon nanotubes
CNT
MWCNT
NM-401
rat
title Pulmonary Toxicity of Long, Thick MWCNT and Very Long, Thin Carboxylated MWCNT Aerosols Following 28 Days Whole-Body Exposure
title_full Pulmonary Toxicity of Long, Thick MWCNT and Very Long, Thin Carboxylated MWCNT Aerosols Following 28 Days Whole-Body Exposure
title_fullStr Pulmonary Toxicity of Long, Thick MWCNT and Very Long, Thin Carboxylated MWCNT Aerosols Following 28 Days Whole-Body Exposure
title_full_unstemmed Pulmonary Toxicity of Long, Thick MWCNT and Very Long, Thin Carboxylated MWCNT Aerosols Following 28 Days Whole-Body Exposure
title_short Pulmonary Toxicity of Long, Thick MWCNT and Very Long, Thin Carboxylated MWCNT Aerosols Following 28 Days Whole-Body Exposure
title_sort pulmonary toxicity of long thick mwcnt and very long thin carboxylated mwcnt aerosols following 28 days whole body exposure
topic nanotoxicology
carbon nanotubes
CNT
MWCNT
NM-401
rat
url https://www.mdpi.com/2305-6304/13/5/401
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