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

Niels Hadrup (1) , Kristina Bram Knudsen (1) , Marie Carriere (2) , Martine Mayne-L'Hermite (3) , Laure Bobyk (2) , Soline Allard (3) , Frédéric Miserque (4) , Baptiste Pibaleau (3) , Mathieu Pinault (3) , Håkan Wallin (1, 5) , Ulla Vogel (1, 6)

1 NRCWE - National Research Centre for the Working Environment
2 CIBEST - Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie
3 LEDNA - Laboratoire Edifices Nanométriques
4 SCCME - Service de la Corrosion et du Comportement des Matériaux dans leur Environnement
5 STAMI - National Institute of Occupational Health (STAMI)
6 DTU-FOOD - National Food Institute [Søborg]

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 was 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; MWCNTs; Nanomaterial; pulmonary; safe-by-design; oxidation

Domains: Chemical Sciences; Material chemistry; Life Sciences [q-bio]; Toxicology

Niels Hadrup, Kristina Bram Knudsen, Marie Carriere, Martine Mayne-L'Hermite, Laure Bobyk, et al.. Safe-by-design strategies for lowering the genotoxicity and pulmonary inflammation of multiwalled carbon nanotubes: Reduction of length and the introduction of COOH groups. Environmental Toxicology and Pharmacology, 2021, 87, pp.103702. ⟨10.1016/j.etap.2021.103702⟩. ⟨cea-03284985⟩