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Physicochemical predictors of Multi-Walled Carbon Nanotube-induced pulmonary histopathology and toxicity one year after pulmonary deposition of 11 different Multi-Walled Carbon Nanotubes in mice
- Source :
- Basic & Clinical Pharmacology & Toxicology, Knudsen, K B, Berthing, T, Jackson, P, Poulsen, S S, Mortensen, A, Jacobsen, N R, Skaug, V, Szarek, J, Hougaard, K S, Wolff, H, Wallin, H & Vogel, U B 2019, ' Physicochemical predictors of Multi-Walled Carbon Nanotube-induced pulmonary histopathology and toxicity one year after pulmonary deposition of 11 different Multi-Walled Carbon Nanotubes in mice ', Basic and Clinical Pharmacology and Toxicology, vol. 124, no. 2, pp. 211-227 . https://doi.org/10.1111/bcpt.13119
- Publication Year :
- 2018
-
Abstract
- Multi-walled carbon nanotubes (MWCNT) are widely used nanomaterials that cause pulmonary toxicity upon inhalation. The physicochemical properties of MWCNT vary greatly, which makes general safety evaluation challenging to conduct. Identification of the toxicity-inducing physicochemical properties of MWCNT is therefore of great importance. We have evaluated histological changes in lung tissue 1 year after a single intratracheal instillation of 11 well-characterized MWCNT in female C57BL/6N BomTac mice. Genotoxicity in liver and spleen was evaluated by the comet assay. The dose of 54 μg MWCNT corresponds to three times the estimated dose accumulated during a work life at a NIOSH recommended exposure limit (0.001 mg/m3). Short and thin MWCNT were observed as agglomerates in lung tissue 1 year after exposure, whereas thicker and longer MWCNT were detected as single fibres, suggesting biopersistence of both types of MWCNT. The thin and entangled MWCNT induced varying degree of pulmonary inflammation, in terms of lymphocytic aggregates, granulomas and macrophage infiltration, whereas two thick and straight MWCNT did not. By multiple regression analysis, larger diameter and higher content of iron predicted less histopathological changes, whereas higher cobalt content significantly predicted more histopathological changes. No MWCNT-related fibrosis or tumours in the lungs or pleura was found. One thin and entangled MWCNT induced increased levels of DNA strand breaks in liver; however, no physicochemical properties could be related to genotoxicity. This study reveals physicochemical-dependent difference in MWCNT-induced long-term, pulmonary histopathological changes. Identification of diameter size and cobalt content as important for MWCNT toxicity provides clues for designing MWCNT, which cause reduced human health effects following pulmonary exposure.
- Subjects :
- Pulmonary toxicity
Toxicology
medicine.disease_cause
030226 pharmacology & pharmacy
law.invention
Mice
0302 clinical medicine
Biodistribution
Fibrosis
law
Lung
Granuloma
Inhalation
Behavior, Animal
Chemistry
in vivo
macrophage infiltration
General Medicine
3. Good health
Lymphocytic aggregate
Liver
Basic Toxicology
Toxicity
Female
Original Article
Amyloid
Carbon nanotubes
Carbon nanotube
In vivo
03 medical and health sciences
SDG 3 - Good Health and Well-being
medicine
Animals
Macrophage infiltration
biodistribution
Pharmacology
carbon nanotubes
Mutagenicity Tests
Nanotubes, Carbon
DNA
Pneumonia
medicine.disease
Comet assay
Mice, Inbred C57BL
lymphocytic aggregate
Biophysics
ORIGINAL ARTICLES
030217 neurology & neurosurgery
Genotoxicity
Spleen
DNA Damage
Subjects
Details
- ISSN :
- 17427843
- Volume :
- 124
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Basicclinical pharmacologytoxicology
- Accession number :
- edsair.doi.dedup.....3182f6d05ffc4f0e8b36ead1c0066c4e