The pulmonary toxicity of carboxylated or aminated multi-walled carbon nanotubes in mice is determined by the prior purification method.


Journal

Particle and fibre toxicology
ISSN: 1743-8977
Titre abrégé: Part Fibre Toxicol
Pays: England
ID NLM: 101236354

Informations de publication

Date de publication:
26 11 2020
Historique:
received: 03 07 2020
accepted: 11 11 2020
entrez: 27 11 2020
pubmed: 28 11 2020
medline: 25 6 2021
Statut: epublish

Résumé

Inhalation of multi-walled carbon nanotubes (MWCNTs) poses a potential risk to human health. In order to safeguard workers and consumers, the toxic properties of MWCNTs need to be identified. Functionalization has been shown to either decrease or increase MWCNT-related pulmonary injury, depending on the type of modification. We, therefore, investigated both acute and chronic pulmonary toxicity of a library of MWCNTs derived from a common pristine parent compound (NC7000). MWCNTs were thermally or chemically purified and subsequently surface functionalized by carboxylation or amination. To evaluate pulmonary toxicity, male C57BL6 mice were dosed via oropharyngeal aspiration with either 1.6 or 4 mg/kg of each MWCNT type. Mitsui-7 MWCNT was used as a positive control. Necropsy was performed at days 3 and 60 post-exposure to collect bronchoalveolar lavage fluid (BALF) and lungs. At day 3 all MWCNTs increased the number of neutrophils in BALF. Chemical purification had a greater effect on pro-inflammatory cytokines (IL-1β, IL-6, CXCL1) in BALF, while thermal purification had a greater effect on pro-fibrotic cytokines (CCL2, OPN, TGF-β1). At day 60, thermally purified, carboxylated MWCNTs had the strongest effect on lymphocyte numbers in BALF. Thermally purified MWCNTs caused the greatest increase in LDH and total protein in BALF. Furthermore, the thermally purified and carboxyl- or amine-functionalized MWCNTs caused the greatest number of granulomatous lesions in the lungs. The physicochemical characteristics mainly associated with increased toxicity of the thermally purified derivatives were decreased surface defects and decreased amorphous content as indicated by Raman spectroscopy. These data demonstrate that the purification method is an important determinant of lung toxicity induced by carboxyl- and amine-functionalized MWCNTs.

Sections du résumé

BACKGROUND
Inhalation of multi-walled carbon nanotubes (MWCNTs) poses a potential risk to human health. In order to safeguard workers and consumers, the toxic properties of MWCNTs need to be identified. Functionalization has been shown to either decrease or increase MWCNT-related pulmonary injury, depending on the type of modification. We, therefore, investigated both acute and chronic pulmonary toxicity of a library of MWCNTs derived from a common pristine parent compound (NC7000).
METHODS
MWCNTs were thermally or chemically purified and subsequently surface functionalized by carboxylation or amination. To evaluate pulmonary toxicity, male C57BL6 mice were dosed via oropharyngeal aspiration with either 1.6 or 4 mg/kg of each MWCNT type. Mitsui-7 MWCNT was used as a positive control. Necropsy was performed at days 3 and 60 post-exposure to collect bronchoalveolar lavage fluid (BALF) and lungs.
RESULTS
At day 3 all MWCNTs increased the number of neutrophils in BALF. Chemical purification had a greater effect on pro-inflammatory cytokines (IL-1β, IL-6, CXCL1) in BALF, while thermal purification had a greater effect on pro-fibrotic cytokines (CCL2, OPN, TGF-β1). At day 60, thermally purified, carboxylated MWCNTs had the strongest effect on lymphocyte numbers in BALF. Thermally purified MWCNTs caused the greatest increase in LDH and total protein in BALF. Furthermore, the thermally purified and carboxyl- or amine-functionalized MWCNTs caused the greatest number of granulomatous lesions in the lungs. The physicochemical characteristics mainly associated with increased toxicity of the thermally purified derivatives were decreased surface defects and decreased amorphous content as indicated by Raman spectroscopy.
CONCLUSIONS
These data demonstrate that the purification method is an important determinant of lung toxicity induced by carboxyl- and amine-functionalized MWCNTs.

Identifiants

pubmed: 33243293
doi: 10.1186/s12989-020-00390-y
pii: 10.1186/s12989-020-00390-y
pmc: PMC7690083
doi:

Substances chimiques

Air Pollutants 0
Cytokines 0
Nanotubes, Carbon 0
Transforming Growth Factor beta1 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

60

Subventions

Organisme : NIEHS NIH HHS
ID : R01 ES031253
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES007046
Pays : United States

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Auteurs

Alexia J Taylor-Just (AJ)

Toxicology Program, Department of Biological Sciences, North Carolina State University, 850 Main Campus Drive, Suite 1104, Toxicology Building, Raleigh, NC, 27606, USA.

Mark D Ihrie (MD)

Toxicology Program, Department of Biological Sciences, North Carolina State University, 850 Main Campus Drive, Suite 1104, Toxicology Building, Raleigh, NC, 27606, USA.

Katherine S Duke (KS)

Toxicology Program, Department of Biological Sciences, North Carolina State University, 850 Main Campus Drive, Suite 1104, Toxicology Building, Raleigh, NC, 27606, USA.

Ho Young Lee (HY)

Toxicology Program, Department of Biological Sciences, North Carolina State University, 850 Main Campus Drive, Suite 1104, Toxicology Building, Raleigh, NC, 27606, USA.

Dorothy J You (DJ)

Toxicology Program, Department of Biological Sciences, North Carolina State University, 850 Main Campus Drive, Suite 1104, Toxicology Building, Raleigh, NC, 27606, USA.

Salik Hussain (S)

Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, WV, USA.

Vamsi K Kodali (VK)

Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, WV, USA.

Christina Ziemann (C)

Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany.

Otto Creutzenberg (O)

Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany.

Adriana Vulpoi (A)

Interdisciplinary Research Institute in Bio-Nano-Sciences, Babes Bolyai University, Cluj-Napoca, Romania.

Flaviu Turcu (F)

Interdisciplinary Research Institute in Bio-Nano-Sciences, Babes Bolyai University, Cluj-Napoca, Romania.

Monica Potara (M)

Interdisciplinary Research Institute in Bio-Nano-Sciences, Babes Bolyai University, Cluj-Napoca, Romania.

Milica Todea (M)

Interdisciplinary Research Institute in Bio-Nano-Sciences, Babes Bolyai University, Cluj-Napoca, Romania.
Department of Molecular Sciences, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.

Sybille van den Brule (S)

Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCL), Brussels, Belgium.

Dominique Lison (D)

Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCL), Brussels, Belgium.

James C Bonner (JC)

Toxicology Program, Department of Biological Sciences, North Carolina State University, 850 Main Campus Drive, Suite 1104, Toxicology Building, Raleigh, NC, 27606, USA. jcbonner@ncsu.edu.

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