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

Hadrup, Niels; Knudsen, Kristina Bram; Carrière, Marie; Mayne-l'Hermite, M.; Bobyk, Laure; Allard, Soline; Miserque, F.; Pibaleau, Baptiste; Pinault, Mathieu; Wallin, Håkan; Vogel, Ulla

doi:10.1016/j.etap.2021.103702

Cited by 8 publications

(5 citation statements)

References 56 publications

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“…On the other hand, introduction of COOH-groups onto the structure of one type of MWCNT suppressed the levels of oxidative DNA damage in A549 cells, although MWCNTs with high COOH content were able to induce DNA damage in the alkaline comet assay. However, COOH-modified MWCNTs induced a higher acellular ROS production than pristine MWCNTs [ 73 ].…”

Section: Discussionmentioning

confidence: 99%

Surface functionalization and size modulate the formation of reactive oxygen species and genotoxic effects of cellulose nanofibrils

et al. 2022

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Background Cellulose nanofibrils (CNFs) have emerged as a sustainable and environmentally friendly option for a broad range of applications. The fibrous nature and high biopersistence of CNFs call for a thorough toxicity assessment, but it is presently unclear which physico-chemical properties could play a role in determining the potential toxic response to CNF. Here, we assessed whether surface composition and size could modulate the genotoxicity of CNFs in human bronchial epithelial BEAS-2B cells. We examined three size fractions (fine, medium and coarse) of four CNFs with different surface chemistry: unmodified (U-CNF) and functionalized with 2,2,6,6-tetramethyl-piperidin-1-oxyl (TEMPO) (T-CNF), carboxymethyl (C-CNF) and epoxypropyltrimethylammonium chloride (EPTMAC) (E-CNF). In addition, the source fibre was also evaluated as a non-nanosized material. Results The presence of the surface charged groups in the functionalized CNF samples resulted in higher amounts of individual nanofibrils and less aggregation compared with the U-CNF. T-CNF was the most homogenous, in agreement with its high surface group density. However, the colloidal stability of all the CNF samples dropped when dispersed in cell culture medium, especially in the case of T-CNF. CNF was internalized by a minority of BEAS-2B cells. No remarkable cytotoxic effects were induced by any of the cellulosic materials. All cellulosic materials, except the medium fraction of U-CNF, induced a dose-dependent intracellular formation of reactive oxygen species (ROS). The fine fraction of E-CNF, which induced DNA damage (measured by the comet assay) and chromosome damage (measured by the micronucleus assay), and the coarse fraction of C-CNF, which produced chromosome damage, also showed the most effective induction of ROS in their respective size fractions. Conclusions Surface chemistry and size modulate the in vitro intracellular ROS formation and the induction of genotoxic effects by fibrillated celluloses. One cationic (fine E-CNF) and one anionic (coarse C-CNF) CNF showed primary genotoxic effects, possibly partly through ROS generation. However, the conclusions cannot be generalized to all types of CNFs, as the synthesis process and the dispersion method used for testing affect their physico-chemical properties and, hence, their toxic effects.

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Section: Discussionmentioning

confidence: 99%

Surface functionalization and size modulate the formation of reactive oxygen species and genotoxic effects of cellulose nanofibrils

et al. 2022

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“…A pilot study was designed based on our previous studies on MWCNT toxicity [ 36 – 41 ]. The dimensions of the GaP NWs used in the pilot study (diameter 78 ± 10 nm, length 1.8 μm ± 3.2 μm) were similar to the dimensions of the MWCNTs NM-401 (67 ± 24 nm diameter, length 4 ± 2.4 μm) and Mitsui-7 (74 ± 28 nm diameter, length 5.7 ± 0.49 μm), which induce inflammation at 6 to 18 µg/mouse [ 36 , 37 , 42 , 43 ].…”

Section: Resultsmentioning

confidence: 99%

“…To evaluate the inflammatory response to GaP NW exposure, inflammation was assessed in terms of the cellular composition in BAL fluid 1, 3, 28 days and 3 months post-exposure, and compared to MWCNT-induced inflammation. A single dose of carbon black (162 µg) was included as a benchmark of particle-induced pulmonary inflammation to allow comparison with previous studies [ 39 , 41 , 47 , 56 – 65 ].…”

Section: Resultsmentioning

confidence: 99%

Pulmonary toxicity and translocation of gallium phosphide nanowires to secondary organs following pulmonary exposure in mice

Berthing,

Lard,

Danielsen

et al. 2023

J Nanobiotechnol

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Background III-V semiconductor nanowires are envisioned as being integrated in optoelectronic devices in the near future. However, the perspective of mass production of these nanowires raises concern for human safety due to their asbestos- and carbon nanotube-like properties, including their high aspect ratio shape. Indeed, III-V nanowires have similar dimensions as Mitsui-7 multi-walled carbon nanotubes, which induce lung cancer by inhalation in rats. It is therefore urgent to investigate the toxicological effects following lung exposure to III-V nanowires prior to their use in industrial production, which entails risk of human exposure. Here, female C57BL/6J mice were exposed to 2, 6, and 18 µg (0.12, 0.35 and 1.1 mg/kg bw) of gallium phosphide (III-V) nanowires (99 nm diameter, 3.7 μm length) by intratracheal instillation and the toxicity was investigated 1, 3, 28 days and 3 months after exposure. Mitsui-7 multi-walled carbon nanotubes and carbon black Printex 90 nanoparticles were used as benchmark nanomaterials. Results Gallium phosphide nanowires induced genotoxicity in bronchoalveolar lavage cells and acute inflammation with eosinophilia observable both in bronchoalveolar lavage and lung tissue (1 and 3 days post-exposure). The inflammatory response was comparable to the response following exposure to Mitsui-7 multi-walled carbon nanotubes at similar dose levels. The nanowires underwent partial dissolution in the lung resulting in thinner nanowires, with an estimated in vivo half-life of 3 months. Despite the partial dissolution, nanowires were detected in lung, liver, spleen, kidney, uterus and brain 3 months after exposure. Conclusion Pulmonary exposure to gallium phosphide nanowires caused similar toxicological effects as the multi-walled carbon nanotube Mitsui-7. Graphical Abstract

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“…For instance, sonication can break multi-walled carbon nanotubes (MWCNT), causing a reduction of their length [ 27 ], and therefore leading to different toxicity profiles than the MWCNT that humans would be exposed to. Sonication has been used to produce MWCNTs with different lengths from a same initial batch of MWCNTs [ 28 , 29 ], and Hadrup et al (2021) concluded that the length of the MWCNT is a major determinant of its toxicity [ 29 ]. Therefore, when assessing hazard properties of CNTs in vitro, sonication should be limited as much as possible, and in case sonication is used, NM physicochemical properties should be verified to ensure they still maintain exposure-relevant characteristics.…”

Section: Challenges Of Testing Nms In Vitro For Sbd Applicabilitymentioning

confidence: 99%

The State of the Art and Challenges of In Vitro Methods for Human Hazard Assessment of Nanomaterials in the Context of Safe-by-Design

et al. 2023

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The Safe-by-Design (SbD) concept aims to facilitate the development of safer materials/products, safer production, and safer use and end-of-life by performing timely SbD interventions to reduce hazard, exposure, or both. Early hazard screening is a crucial first step in this process. In this review, for the first time, commonly used in vitro assays are evaluated for their suitability for SbD hazard testing of nanomaterials (NMs). The goal of SbD hazard testing is identifying hazard warnings in the early stages of innovation. For this purpose, assays should be simple, cost-effective, predictive, robust, and compatible. For several toxicological endpoints, there are indications that commonly used in vitro assays are able to predict hazard warnings. In addition to the evaluation of assays, this review provides insights into the effects of the choice of cell type, exposure and dispersion protocol, and the (in)accurate determination of dose delivered to cells on predictivity. Furthermore, compatibility of assays with challenging advanced materials and NMs released from nano-enabled products (NEPs) during the lifecycle is assessed, as these aspects are crucial for SbD hazard testing. To conclude, hazard screening of NMs is complex and joint efforts between innovators, scientists, and regulators are needed to further improve SbD hazard testing.

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

Cited by 8 publications

References 56 publications

Surface functionalization and size modulate the formation of reactive oxygen species and genotoxic effects of cellulose nanofibrils

Surface functionalization and size modulate the formation of reactive oxygen species and genotoxic effects of cellulose nanofibrils

Pulmonary toxicity and translocation of gallium phosphide nanowires to secondary organs following pulmonary exposure in mice

The State of the Art and Challenges of In Vitro Methods for Human Hazard Assessment of Nanomaterials in the Context of Safe-by-Design

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