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

• Published in: Environmental toxicology and pharmacology 2021-10, Vol.87, p.103702, Article 103702
• Main Authors: Hadrup, Niels, Knudsen, Kristina Bram, Carriere, Marie, Mayne-L’Hermite, Martine, Bobyk, Laure, Allard, Soline, Miserque, Frédéric, Pibaleau, Baptiste, Pinault, Mathieu, Wallin, Håkan, Vogel, Ulla
• Format: Article
• Language: English
• Subjects: A549 Cells; Animals; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - cytology; Chemical Sciences; CNT; Comet Assay; DNA Damage; Drug Design; Female; Humans; Inflammation - chemically induced; Inflammation - immunology; Life Sciences; Lung - drug effects; Lung - immunology; Material chemistry; Mice; Mice, Inbred C57BL; Micronucleus Tests; Mutagens - chemistry; Mutagens - toxicity; MWCNT; Nanomaterial; Nanotubes, Carbon - chemistry; Nanotubes, Carbon - toxicity; Neutrophils - drug effects; Neutrophils - immunology; Oxidation; Pulmonary; Safe-by-design; Toxicology
• ISSN: 1382-6689; 1872-7077
• DOI: 10.1016/j.etap.2021.103702

•We investigated safe-by-design strategies to lower lung toxicity of carbon nanotubes.•Carbon nanotubes were either shortened or had COOH-groups added.•Both strategies lowered pulmonary inflammation measured as neutrophils in lung.•Genotoxicity of long carbon nanotubes was lowered by either strategy.•Overall, the toxicity was lowered, but not eliminated, by either strategy. 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.