Safety Assessment of Graphene-Based Materials: Human Health and Environment

A special issue of Nanomaterials (ISSN 2079-4991).

Deadline for manuscript submissions: closed (15 March 2022) | Viewed by 20222

Special Issue Editors


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Guest Editor
Department of Life Science, Università degli Studi di Trieste, Trieste, Italy
Interests: marine toxins; algal toxins; toxicology; pharmacology; skin toxicity; oral toxicity; inflammation; mechanisms of toxicity; methods of detection

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Co-Guest Editor
Department of Life Sciences, University of Trieste, Trieste, Italy
Interests: Carbon based nanomaterials; Ecotoxicology; Ecophysiology; Environmental toxicology; Environmental pollution; Graphene; Graphene-related materials; Graphene environmental fate; Graphene biodegradability; Plant biology

Special Issue Information

Dear Colleagues,

Graphene-Based Materials (GBMs) are a novel class of carbon-based nanomaterials characterized by extraordinary physicochemical properties that are the basis for a wide range of applications. These are used in various fields including nanoelectronics, energy technology, and biomedicine. Increasing effort is being made to produce novel GBMs with modified and expanded properties. However, because of the expected significant increase in the GBM market over the next few years and the concomitant release of GBM-containing nanoparticles into the environment, safety issues related to human health and the environment need to be addressed.

The increasing widespread interest and use of GBMs necessitates a comprehensive evaluation of the potential impacts of these materials on human health and the environment. Even though a large body of knowledge on the (eco)toxicological impact of GBMs exists, toxicological data are still insufficient to draw conclusions on their safety for human health and the environment. In addition, a special focus is still needed to understand the physicochemical properties influencing the (eco)toxicological effects of GBMs in compliance with the safe-by-design principle. This Special Issue of Nanomaterials, “Safety Assessment of Graphene-Based Materials: Human Health and the Environment”, aims to present a compilation of articles that demonstrate the continuous effort being made to assess the safety of GBMs for both humans and the environment with the ultimate goal of implementing the hazard characterization of these materials.

Dr. Marco Pelin
Dr. Fabio Candotto Carniel
Guest Editors

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Keywords

  • graphene-based materials
  • graphene
  • nanotoxicology
  • ecotoxicology
  • hazard characterization
  • mechanisms of toxicity
  • safe-by-design

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Published Papers (6 papers)

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Research

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17 pages, 2698 KiB  
Article
Structure–Activity Relationship of Graphene-Based Materials: Impact of the Surface Chemistry, Surface Specific Area and Lateral Size on Their In Vitro Toxicity
by Salma Achawi, Bruno Feneon, Jérémie Pourchez and Valérie Forest
Nanomaterials 2021, 11(11), 2963; https://doi.org/10.3390/nano11112963 - 4 Nov 2021
Cited by 20 | Viewed by 2136
Abstract
Predictive toxicity and structure–activity relationships (SARs) are raising interest since the number of nanomaterials has become unmanageable to assess their toxicity with a classical case-by-case approach. Graphene-based materials (GBMs) are among the most promising nanomaterials of this decade and their application might lead [...] Read more.
Predictive toxicity and structure–activity relationships (SARs) are raising interest since the number of nanomaterials has become unmanageable to assess their toxicity with a classical case-by-case approach. Graphene-based materials (GBMs) are among the most promising nanomaterials of this decade and their application might lead to several innovations. However, their toxicity impact needs to be thoroughly assessed. In this regard, we conducted a study on 22 GBMs to investigate their potential SARs by performing a complete physicochemical characterization and in vitro toxicity assessment (on RAW264.7 cells). We used GBMs of variable lateral size (0.5–38 µm), specific surface area (SSA, 30–880 m²/g), and surface oxidation (2–17%). We observed that reduced graphene oxides (RGOs) were more reactive than graphene nanoplatelets (GNPs), potentially highlighting the role of GBM’s surface chemistry and surface defects density in their biological impact. We also observed that for GNPs, a smaller lateral size caused higher cytotoxicity. Lastly, GBMs showing a SSA higher than 200 m²/g were found to induce a higher ROS production. Mechanistic explanations are proposed in the discussion. In conclusion, pairing a full physicochemical characterization with a standardized toxicity assessment of a large set of samples allowed us to clarify SARs and provide an additional step toward safe-by-design GBMs. Full article
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17 pages, 4507 KiB  
Article
Carbon-Based Nanomaterials Increase Reactivity of Primary Monocytes towards Various Bacteria and Modulate Their Differentiation into Macrophages
by Tereza Svadlakova, Martina Kolackova, Radka Vankova, Rumeysa Karakale, Andrea Malkova, Pavel Kulich, Frantisek Hubatka, Pavlina Turanek-Knotigova, Irena Kratochvilova, Milan Raska, Jan Krejsek and Jaroslav Turanek
Nanomaterials 2021, 11(10), 2510; https://doi.org/10.3390/nano11102510 - 27 Sep 2021
Cited by 11 | Viewed by 2896
Abstract
The evaluation of carbon-based nanomaterials’ (C-BNMs’) interactions with the immune system, notably their ability to cause inflammation, is a critical step in C-BNM health risk assessment. Particular attention should be given to those C-BNMs that do not cause direct cytotoxicity or inflammation on [...] Read more.
The evaluation of carbon-based nanomaterials’ (C-BNMs’) interactions with the immune system, notably their ability to cause inflammation, is a critical step in C-BNM health risk assessment. Particular attention should be given to those C-BNMs that do not cause direct cytotoxicity or inflammation on their own. However, the intracellular presence of these non-biodegradable nanomaterials could dysregulate additional cell functions. This is even more crucial in the case of phagocytes, which are the main mediators of defensive inflammation towards pathogens. Hence, our study was focused on multi-walled carbon nanotubes (MWCNTs) and two different types of graphene platelets (GPs) and whether their intracellular presence modulates a proinflammatory response from human primary monocytes towards common pathogens. Firstly, we confirmed that all tested C-BNMs caused neither direct cytotoxicity nor the release of tumour necrosis factor α (TNF-α), interleukin (IL)-6 or IL-10. However, such pre-exposed monocytes showed increased responsiveness to additional bacterial stimuli. In response to several types of bacteria, monocytes pre-treated with GP1 produced a significantly higher quantity of TNF-α, IL-6 and IL-10. Monocytes pre-treated with MWCNTs produced increased levels of IL-10. All the tested C-BNMs enhanced monocyte phagocytosis and accelerated their differentiation towards macrophages. This study confirms the immunomodulatory potential of C-BNMs. Full article
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14 pages, 1916 KiB  
Article
Partial Reversibility of the Cytotoxic Effect Induced by Graphene-Based Materials in Skin Keratinocytes
by Marco Pelin, Hazel Lin, Arianna Gazzi, Silvio Sosa, Cristina Ponti, Amaya Ortega, Amaia Zurutuza, Ester Vázquez, Maurizio Prato, Aurelia Tubaro and Alberto Bianco
Nanomaterials 2020, 10(8), 1602; https://doi.org/10.3390/nano10081602 - 15 Aug 2020
Cited by 12 | Viewed by 3070
Abstract
In the frame of graphene-based material (GBM) hazard characterization, particular attention should be given to the cutaneous effects. Hence, this study investigates if HaCaT skin keratinocytes exposed to high concentrations of few-layer graphene (FLG) or partially dehydrated graphene oxide (d-GO) for a short [...] Read more.
In the frame of graphene-based material (GBM) hazard characterization, particular attention should be given to the cutaneous effects. Hence, this study investigates if HaCaT skin keratinocytes exposed to high concentrations of few-layer graphene (FLG) or partially dehydrated graphene oxide (d-GO) for a short time can recover from the cytotoxic insult, measured by means of cell viability, mitochondrial damage and oxidative stress, after GBM removal from the cell medium. When compared to 24 or 72 h continuous exposure, recovery experiments suggest that the cytotoxicity induced by 24 h exposure to GBM is only partially recovered after 48 h culture in GBM-free medium. This partial recovery, higher for FLG as compared to GO, is not mediated by autophagy and could be the consequence of GBM internalization into cells. The ability of GBMs to be internalized inside keratinocytes together with the partial reversibility of the cellular damage is important in assessing the risk associated with skin exposure to GBM-containing devices. Full article
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18 pages, 4135 KiB  
Article
Proinflammatory Effect of Carbon-Based Nanomaterials: In Vitro Study on Stimulation of Inflammasome NLRP3 via Destabilisation of Lysosomes
by Tereza Svadlakova, Frantisek Hubatka, Pavlina Turanek Knotigova, Pavel Kulich, Josef Masek, Jan Kotoucek, Jan Macak, Martin Motola, Martin Kalbac, Martina Kolackova, Radka Vankova, Petra Vicherkova, Andrea Malkova, Pavlina Simeckova, Yuri Volkov, Adriele Prina-Mello, Irena Kratochvilova, Zdenek Fiala, Milan Raska, Jan Krejsek and Jaroslav Turanekadd Show full author list remove Hide full author list
Nanomaterials 2020, 10(3), 418; https://doi.org/10.3390/nano10030418 - 27 Feb 2020
Cited by 30 | Viewed by 5144
Abstract
Carbon-based nanomaterials (C-BNM) have recently attracted an increased attention as the materials with potential applications in industry and medicine. Bioresistance and proinflammatory potential of C-BNM is the main obstacle for their medicinal application which was documented in vivo and in vitro. However, there [...] Read more.
Carbon-based nanomaterials (C-BNM) have recently attracted an increased attention as the materials with potential applications in industry and medicine. Bioresistance and proinflammatory potential of C-BNM is the main obstacle for their medicinal application which was documented in vivo and in vitro. However, there are still limited data especially on graphene derivatives such as graphene platelets (GP). In this work, we compared multi-walled carbon nanotubes (MWCNT) and two different types of pristine GP in their potential to activate inflammasome NLRP3 (The nod-like receptor family pyrin domain containing 3) in vitro. Our study is focused on exposure of THP-1/THP1-null cells and peripheral blood monocytes to C-BNM as representative models of canonical and alternative pathways, respectively. Although all nanomaterials were extensively accumulated in the cytoplasm, increasing doses of all C-BNM did not lead to cell death. We observed direct activation of NLRP3 via destabilization of lysosomes and release of cathepsin B into cytoplasm only in the case of MWCNTs. Direct activation of NLRP3 by both GP was statistically insignificant but could be induced by synergic action with muramyl dipeptide (MDP), as a representative molecule of the family of pathogen-associated molecular patterns (PAMPs). This study demonstrates a possible proinflammatory potential of GP and MWCNT acting through NLRP3 activation. Full article
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13 pages, 2586 KiB  
Article
Few Layer Graphene Does Not Affect Cellular Homeostasis of Mouse Macrophages
by Sowmya Malanagahalli, Diane Murera, Cristina Martín, Hazel Lin, Nadége Wadier, Hélène Dumortier, Ester Vázquez and Alberto Bianco
Nanomaterials 2020, 10(2), 228; https://doi.org/10.3390/nano10020228 - 28 Jan 2020
Cited by 16 | Viewed by 3096
Abstract
Graphene-related materials (GRMs) are widely used in various applications due to their unique properties. A growing number of reports describe the impact of different carbon nanomaterials, including graphene oxide (GO), reduced GO (rGO), and carbon nanotubes (CNT), on immune cells, but there is [...] Read more.
Graphene-related materials (GRMs) are widely used in various applications due to their unique properties. A growing number of reports describe the impact of different carbon nanomaterials, including graphene oxide (GO), reduced GO (rGO), and carbon nanotubes (CNT), on immune cells, but there is still a very limited number of studies on graphene. In this work, we investigated the biological responses of few layer graphene (FLG) on mouse macrophages (bone marrow derived macrophages, BMDMs), which are part of the first line of defense in innate immunity. In particular, our paper describes our findings of short-term FLG treatment in BMDMs with a focus on observing material internalization and changes in general cell morphology. Subsequent investigation of cytotoxicity parameters showed that increasing doses of FLG did not hamper the viability of cells and did not trigger inflammatory responses. Basal level induced autophagic activity sufficed to maintain the cellular homeostasis of FLG treated cells. Our results shed light on the impact of FLG on primary macrophages and show that FLG does not elicit immunological responses leading to cell death. Full article
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Review

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30 pages, 1476 KiB  
Review
Genotoxicity of Graphene-Based Materials
by Josefa Domenech, Adriana Rodríguez-Garraus, Adela López de Cerain, Amaya Azqueta and Julia Catalán
Nanomaterials 2022, 12(11), 1795; https://doi.org/10.3390/nano12111795 - 24 May 2022
Cited by 13 | Viewed by 2725
Abstract
Graphene-based materials (GBMs) are a broad family of novel carbon-based nanomaterials with many nanotechnology applications. The increasing market of GBMs raises concerns on their possible impact on human health. Here, we review the existing literature on the genotoxic potential of GBMs over the [...] Read more.
Graphene-based materials (GBMs) are a broad family of novel carbon-based nanomaterials with many nanotechnology applications. The increasing market of GBMs raises concerns on their possible impact on human health. Here, we review the existing literature on the genotoxic potential of GBMs over the last ten years. A total of 50 articles including in vitro, in vivo, in silico, and human biomonitoring studies were selected. Graphene oxides were the most analyzed materials, followed by reduced graphene oxides. Most of the evaluations were performed in vitro using the comet assay (detecting DNA damage). The micronucleus assay (detecting chromosome damage) was the most used validated assay, whereas only two publications reported results on mammalian gene mutations. The same material was rarely assessed with more than one assay. Despite inhalation being the main exposure route in occupational settings, only one in vivo study used intratracheal instillation, and another one reported human biomonitoring data. Based on the studies, some GBMs have the potential to induce genetic damage, although the type of damage depends on the material. The broad variability of GBMs, cellular systems and methods used in the studies precludes the identification of physico-chemical properties that could drive the genotoxicity response to GBMs. Full article
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