Safe-by-design strategies for lowering the genotoxicity and pulmonary inflammation of multiwalled carbon nanotubes: Reduction of length and the introduction of COOH groups

Environ Toxicol Pharmacol. 2021 Oct:87:103702. doi: 10.1016/j.etap.2021.103702. Epub 2021 Jul 10.

Abstract

Potentially, the toxicity of multiwalled carbon nanotubes (MWCNTs) can be reduced in a safe-by-design strategy. We investigated if genotoxicity and pulmonary inflammation of MWCNTs from the same batch were lowered by a) reducing length and b) introducing COOH-groups into the structure. Mice were administered: 1) long and pristine MWCNT (CNT-long) (3.9 μm); 2) short and pristine CNT (CNT-short) (1 μm); 3) CNT modified with high ratio COOH-groups (CNT-COOH-high); 4) CNT modified with low ratio COOH-groups (CNT-COOH-low). MWCNTs were dosed by intratracheal instillation at 18 or 54 μg/mouse (∼0.9 and 2.7 mg/kg bw). Neutrophils numbers were highest after CNT-long exposure, and both shortening the MWCNT and addition of COOH-groups lowered pulmonary inflammation (day 1 and 28). Likewise, CNT-long induced genotoxicity, which was absent with CNT-short and after introduction of COOH groups. In conclusion, genotoxicity and pulmonary inflammation of MWCNTs were lowered, but not eliminated, by shortening the fibres or introducing COOH-groups.

Keywords: CNT; MWCNT; Nanomaterial; Oxidation; Pulmonary; Safe-by-design.

MeSH terms

  • A549 Cells
  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Comet Assay
  • DNA Damage
  • Drug Design
  • Female
  • Humans
  • Inflammation / chemically induced
  • Inflammation / immunology
  • Lung / drug effects*
  • Lung / immunology
  • Mice
  • Mice, Inbred C57BL
  • Micronucleus Tests
  • Mutagens / chemistry
  • Mutagens / toxicity*
  • Nanotubes, Carbon / chemistry
  • Nanotubes, Carbon / toxicity*
  • Neutrophils / drug effects
  • Neutrophils / immunology

Substances

  • Mutagens
  • Nanotubes, Carbon