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

Kristina B. Knudsen, Trine Berthing, Petra Jackson, Sarah S. Poulsen, Alicja Mortensen, Nicklas R. Jacobsen, Vidar Skaug, Józef Szarek, Karin S. Hougaard, Henrik Wolff, Håkan Wallin, Ulla Birgitte Vogel*

*Corresponding author for this work

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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.
Original languageEnglish
JournalBasic & Clinical Pharmacology & Toxicology
Volume124
Issue number2
Pages (from-to)211-227
ISSN1742-7835
DOIs
Publication statusPublished - 2019

Keywords

  • Biodistribution
  • Carbon nanotubes
  • Granuloma
  • In vivo
  • Lymphocytic aggregate
  • Macrophage infiltration

Cite this

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 & Clinical Pharmacology & Toxicology, 124(2), 211-227. https://doi.org/10.1111/bcpt.13119