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Toxicity of Single-Walled Carbon Nanotubes (SWCNTs): Effect of Lengths, Functional Groups and Electronic Structures Revealed by a Quantitative Toxicogenomics Assay.

ABSTRACT: Single-walled carbon nanotubes (SWCNTs) are a group of widely used carbon-based nanomaterials (CNMs) with various applications, which raise increasing public concerns associated with their potential toxicological effect and risks on human and ecosystems. In this report, we comprehensively evaluated the nanotoxicity of SWCNTs with their relationship to varying lengths, functional groups and electronic structures, by employing both newly established quantitative toxicogenomics test, as well as conventional phenotypic bioassays. The objective is to reveal potential cellular toxicity and mechanisms of SWCNTs at the molecular level, and to probe their potential relationships with their morphological, surface, and electronic properties. The results indicated that DNA damage and oxidative stress were the dominant mechanisms of action for all SWCNTs and, the toxicity level and characteristics varied with length, surface functionalization and electronic structure. Distinguishable molecular toxicity fingerprints were revealed for the two SWCNTs with varying length, with short SWCNT exhibiting higher toxicity level than the long one. In terms of surface properties, SWCNT functionalization, namely carboxylation and hydroxylation, led to elevated overall toxicity, especially genotoxicity, as compared to unmodified SWCNT. Carboxylated SWCNT induced a greater toxicity than the hydroxylated SWCNT. The nucleus is likely the primary target site for long, short, and carboxylated SWCNTs and mechanical perturbation is likely responsible for the DNA damage, specifically related to degradation of the DNA double helix structure. Finally, dramatically different electronic structure-dependent toxicity was observed with metallic SWCNT exerting much higher toxicity than the semiconducting one that exhibited minimal toxicity among all SWCNTs.

SUBMITTER: Jiang T

PROVIDER: S-EPMC7853656 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Toxicity of Single-Walled Carbon Nanotubes (SWCNTs): Effect of Lengths, Functional Groups and Electronic Structures Revealed by a Quantitative Toxicogenomics Assay.

Jiang Tao T Amadei Carlo Alberto CA Gou Na N Lin Yishan Y Lan Jiaqi J Vecitis Chad D CD Gu April Z AZ

Environmental science. Nano 20200429 5

Single-walled carbon nanotubes (SWCNTs) are a group of widely used carbon-based nanomaterials (CNMs) with various applications, which raise increasing public concerns associated with their potential toxicological effect and risks on human and ecosystems. In this report, we comprehensively evaluated the nanotoxicity of SWCNTs with their relationship to varying lengths, functional groups and electronic structures, by employing both newly established quantitative toxicogenomics test, as well as con ...[more]

PMID: 33537148

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Project description:BackgroundA diverse class of engineered nanomaterials (ENMs) exhibiting a wide array of physical-chemical properties that are associated with toxicological effects in experimental animals is in commercial use. However, an integrated framework for human health risk assessment (HHRA) of ENMs has yet to be established. Rodent 2-year cancer bioassays, clinical chemistry, and histopathological endpoints are still considered the 'gold standard' for detecting substance-induced toxicity in animal models. However, the use of data derived from alternative toxicological tools, such as genome-wide expression profiling and in vitro high-throughput assays, are gaining acceptance by the regulatory community for hazard identification and for understanding the underlying mode-of-action. Here, we conducted a case study to evaluate the application of global gene expression data in deriving pathway-based points of departure (PODs) for multi-walled carbon nanotube (MWCNT)-induced lung fibrosis, a non-cancer endpoint of regulatory importance.MethodsGene expression profiles from the lungs of mice exposed to three individual MWCNTs with different physical-chemical properties were used within the framework of an adverse outcome pathway (AOP) for lung fibrosis to identify key biological events linking MWCNT exposure to lung fibrosis. Significantly perturbed pathways were categorized along the key events described in the AOP. Benchmark doses (BMDs) were calculated for each perturbed pathway and were used to derive transcriptional BMDs for each MWCNT.ResultsSimilar biological pathways were perturbed by the different MWCNT types across the doses and post-exposure time points studied. The pathway BMD values showed a time-dependent trend, with lower BMDs for pathways perturbed at the earlier post-exposure time points (24 h, 3d). The transcriptional BMDs were compared to the apical BMDs derived by the National Institute for Occupational Safety and Health (NIOSH) using alveolar septal thickness and fibrotic lesions endpoints. We found that regardless of the type of MWCNT, the BMD values for pathways associated with fibrosis were 14.0-30.4 μg/mouse, which are comparable to the BMDs derived by NIOSH for MWCNT-induced lung fibrotic lesions (21.0-27.1 μg/mouse).ConclusionsThe results demonstrate that transcriptomic data can be used to as an effective mechanism-based method to derive acceptable levels of exposure to nanomaterials in product development when epidemiological data are unavailable.

Dataset Information

Toxicity of Single-Walled Carbon Nanotubes (SWCNTs): Effect of Lengths, Functional Groups and Electronic Structures Revealed by a Quantitative Toxicogenomics Assay.

Publications

Toxicity of Single-Walled Carbon Nanotubes (SWCNTs): Effect of Lengths, Functional Groups and Electronic Structures Revealed by a Quantitative Toxicogenomics Assay.

Similar Datasets

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