Nanosafety and Nanotoxicology: Current Opportunities and Challenges

A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Environmental Nanoscience and Nanotechnology".

Deadline for manuscript submissions: 23 August 2025 | Viewed by 5679

Special Issue Editors


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Guest Editor
Department of Environment and Health, Istituto Superiore di Sanità, 00161 Rome, Italy
Interests: genotoxicity assays; cytotoxicity tests; DNA and chromosomal damage evaluation; comet assay; nanomaterial safety testing
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Guest Editor
Istituto Superiore Di Sanita, Rome, Italy
Interests: genotoxicity assays; cytotoxicity tests; DNA and chromosomal damage evaluation; comet assay; nanomaterial safety testing

Special Issue Information

Dear Colleagues,

The increasing use of nanomaterials in a wide range of consumer products arises from the need to define a correct strategy for hazard identification and risk assessment. In the last few years, a large amount of data on cytotoxicity and genotoxicity have been published and produced in a wide range of collaborative European-funded projects, but the key mechanisms involved in the cytotoxic and genotoxic responses of nanomaterials are still controversial. In addition, the assay conditions for cytotoxicity and genotoxicity testing are currently being questioned, especially in a regulatory context. In this framework, to facilitate the safe development and use of nanomaterials, the European Commission is supporting the revision/adaptation of the existing safety assessment methods as well as the validation of new approach methodologies and their integration into the risk assessment process (OECD Testing Guidelines and/or Guidance Documents).

This Special Issue is open to contributions on studies on the cytotoxicity and genotoxicity of nanomaterials regarding a) the conditions for cytotoxicity and genotoxicity testing, such as the cell line(s) to be used, the maximum dose/concentration, and the rationale for nanomaterial-positive controls; b) advanced biological models for in vitro cytotoxicity and genotoxicity testing; c) Safe-and Sustainable by-Design (SSbD) approaches; d) in silico methodologies, like QSAR, grouping, and read-across; and e) criteria for the efficient reuse of existing nanosafety data, as recently established through the FAIR (Findable, Accessible, Interoperable, and Reusable) guiding principle.

Dr. Cristina Andreoli
Dr. Andrea Zijno
Guest Editors

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Keywords

  • nanomaterial cytotoxicity testing
  • nanomaterial genotoxicity testing
  • nanosafety
  • new approach methodologies (NAMs)
  • safe and sustainable-by-design (SSbD) approaches
  • in silico methodologies
  • FAIR approach

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Published Papers (5 papers)

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Research

11 pages, 957 KiB  
Article
Comparison of the Level and Mechanisms of Toxicity of Nanoparticles of Underwater Welding in Bioassay with Three Marine Microalgae
by Konstantin Yu. Kirichenko, Konstantin S. Pikula, Vladimir V. Chayka, Alexander V. Gridasov, Igor A. Vakhniuk, Vladislava N. Volkova, Anton V. Pogodaev, Sergei G. Parshin, Yulia S. Parshina, Yuri E. Kalinin, Aleksei S. Kholodov, Sergey M. Ugay, Tatyana Yu. Orlova and Kirill S. Golokhvast
Nanomaterials 2025, 15(7), 518; https://doi.org/10.3390/nano15070518 - 29 Mar 2025
Viewed by 205
Abstract
In this work, the toxicity level of nano- and microparticles obtained by underwater welding was assessed. The toxicity of nano- and microparticles obtained by underwater welding was evaluated on three types of marine microalgae: Heterosigma akashiwo (Ochrophyta), Porphyridium purpureum (Rhodophyta), and Attheya ussuriensis [...] Read more.
In this work, the toxicity level of nano- and microparticles obtained by underwater welding was assessed. The toxicity of nano- and microparticles obtained by underwater welding was evaluated on three types of marine microalgae: Heterosigma akashiwo (Ochrophyta), Porphyridium purpureum (Rhodophyta), and Attheya ussuriensis (Bacillariophyta). The aim was to study the environmental risks associated with the ingress of micro- and nanoparticles of metal oxides into the marine environment. Water samples containing suspensions from wet welding and cutting processes were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) to determine heavy metal concentrations. Biotesting included evaluation of growth inhibition, cell size change, and membrane potential of microalgae using flow cytometry. The results showed that samples APL-1 and APL-2 (flux-cored wire) were the most toxic, causing concentration-dependent growth inhibition of H. akashiwo and A. ussuriensis (p < 0.0001) as well as membrane depolarization. For P. purpureum, ELc and ELw (coated electrodes) samples stimulated growth, indicating species-specific responses. The stability of the nanoparticles and their bioavailability were found to play a key role in the mechanisms of toxicity. The study highlights the need to control the composition of materials for underwater welding and to develop environmentally friendly technologies. The data obtained are important for predicting the long-term effects of pollution of marine ecosystems by substances formed during underwater welding. Full article
(This article belongs to the Special Issue Nanosafety and Nanotoxicology: Current Opportunities and Challenges)
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17 pages, 1955 KiB  
Article
Tattoo Ink Metal Nanoparticles: Assessment of Toxicity In Vitro and with a Novel Human Ex Vivo Model
by Beatrice Battistini, Daniela Lulli, Beatrice Bocca, Maria Luigia Carbone, Carmela Ramondino, Stefano Caimi, Alessio Capone, Ezio Maria Nicodemi, Elena Dellambra, Isabella De Angelis and Cristina Maria Failla
Nanomaterials 2025, 15(4), 270; https://doi.org/10.3390/nano15040270 - 11 Feb 2025
Cited by 1 | Viewed by 905
Abstract
Tattoo inks contain varying amounts of metal nanoparticles (NPs) < 100 nm that, due to their unique physicochemical properties, may have specific biological uptake and cause skin or systemic toxicities. The toxic effects of certified reference standards of metal NPs and samples of [...] Read more.
Tattoo inks contain varying amounts of metal nanoparticles (NPs) < 100 nm that, due to their unique physicochemical properties, may have specific biological uptake and cause skin or systemic toxicities. The toxic effects of certified reference standards of metal NPs and samples of commercially available tattoo inks were investigated using an in vitro system and a novel human ex vivo model. In vitro toxicity was evaluated using vitality assays on human skin cells (HaCaT cell line, primary fibroblasts, and keratinocytes). No toxicity was observed for Al2O3, Cr2O3, Fe2O3, and TiO2 NPs, whereas CuO NPs showed dose-dependent toxicity on HaCaT and primary fibroblasts. Fibroblasts and keratinocytes were also sensitive to high concentrations of ZnO NPs. Reference standards and ink samples were then injected ex vivo into human skin explants using tattoo needles. Histological analysis showed pigment distribution deep in the dermis and close to dermal vessels, suggesting possible systemic diffusion. The presence of an inflammatory infiltrate was also observed. Immunohistochemical analysis showed increased apoptosis and expression of the inflammatory cytokine interleukin-8 in explants specifically tattooed with the reference standard or red ink. Taken together, the results suggest that the tattooing technique leads to exposure to toxic metal NPs and skin damage. Full article
(This article belongs to the Special Issue Nanosafety and Nanotoxicology: Current Opportunities and Challenges)
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19 pages, 4132 KiB  
Article
Exposure to a Titanium Dioxide Product Alters DNA Methylation in Human Cells
by Carlos Wells, Marta Pogribna, Arjun Sharmah, Angel Paredes, Beverly Word, Anil K. Patri, Beverly Lyn-Cook and George Hammons
Nanomaterials 2024, 14(24), 2037; https://doi.org/10.3390/nano14242037 - 19 Dec 2024
Cited by 1 | Viewed by 915
Abstract
The safety of titanium dioxide (TiO2), widely used in foods and personal care products, has been of ongoing concern. Significant toxicity of TiO2 has been reported, suggesting a risk to human health. To evaluate its potential epigenotoxicity, the effect of [...] Read more.
The safety of titanium dioxide (TiO2), widely used in foods and personal care products, has been of ongoing concern. Significant toxicity of TiO2 has been reported, suggesting a risk to human health. To evaluate its potential epigenotoxicity, the effect of exposure to a TiO2 product to which humans could be exposed on DNA methylation, a primary epigenetic mechanism, was investigated using two human cell lines (Caco-2 (colorectal) and HepG2 (liver)) relevant to human exposure. Global methylation was determined by enzyme-linked immunosorbent assay-based immunochemical analysis. Gene promoter methylation was evaluated using EpiTect Methyl II Signature PCR System Array technology. Expression of DNA methyltransferases, MBD2, and URHF1 was quantified by qRT-PCR. A decrease in global DNA methylation was observed in both cell lines. Across the cell lines, seven genes (BNIP3, DNAJC15, GADD45G, GDF15, INSIG1, SCARA3, and TP53) were identified in which promoters were methylated. Changes in promoter methylation were associated with gene expression. Results also revealed aberrant expression of regulatory genes, DNA methyltransferases, MBD2, and UHRF1. Findings from the study clearly demonstrate the impact of TiO2 exposure on DNA methylation in two cell types, supporting the potential involvement of this epigenetic mechanism in its biological responses. Hence, epigenetic studies are critical for complete assessment of potential risk from exposure. Full article
(This article belongs to the Special Issue Nanosafety and Nanotoxicology: Current Opportunities and Challenges)
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14 pages, 1725 KiB  
Article
Toxicological Characteristics of Bacterial Nanocellulose in an In Vivo Experiment—Part 2: Immunological Endpoints, Influence on the Intestinal Barrier and Microbiome
by Vladimir A. Shipelin, Ekaterina A. Skiba, Vera V. Budaeva, Antonina A. Shumakova, Eleonora N. Trushina, Oksana K. Mustafina, Yuliya M. Markova, Nikolay A. Riger, Ivan V. Gmoshinski, Svetlana A. Sheveleva, Sergey A. Khotimchenko and Dmitry B. Nikityuk
Nanomaterials 2024, 14(20), 1678; https://doi.org/10.3390/nano14201678 - 19 Oct 2024
Viewed by 962
Abstract
Bacterial nanocellulose (BNC) is considered a promising alternative to microcrystalline cellulose, as well as an ingredient in low-calorie dietary products. However, the risks of BNC when consumed with food are not well characterized. The aim of this study is to investigate the impact [...] Read more.
Bacterial nanocellulose (BNC) is considered a promising alternative to microcrystalline cellulose, as well as an ingredient in low-calorie dietary products. However, the risks of BNC when consumed with food are not well characterized. The aim of this study is to investigate the impact of BNC on immune function, the intestinal microbiome, intestinal barrier integrity, and allergic sensitization in subacute experiments on rats. Male Wistar rats received BNC with a diet for eight weeks in a dose range of 1–100 mg/kg of body weight. The measurements of serum levels of cytokines, adipokines, iFABP2, indicators of cellular immunity, composition of the intestinal microbiome, and a histological study of the ileal mucosa were performed. In a separate four-week experiment on a model of systemic anaphylaxis to food antigen, BNC at a dose of 100 mg/kg of body weight did not increase the severity of the reaction or change the response of IgG antibodies. Based on dose–response effects on immune function, the non-observed adverse effect level for BNC was less than 100 mg/kg of body weight per day. The effects of BNC on the gut microbiome and the intestinal mucosal barrier were not dose-dependent. Data on the possible presence of prebiotic effects in BNC have been obtained. Full article
(This article belongs to the Special Issue Nanosafety and Nanotoxicology: Current Opportunities and Challenges)
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16 pages, 4410 KiB  
Article
Toxicological Characteristics of Bacterial Nanocellulose in an In Vivo Experiment—Part 1: The Systemic Effects
by Vladimir A. Shipelin, Ekaterina A. Skiba, Vera V. Budaeva, Antonina A. Shumakova, Alexey I. Kolobanov, Ilya E. Sokolov, Kirill Z. Maisaya, Galina V. Guseva, Nikita V. Trusov, Alexander G. Masyutin, Yanina A. Delegan, Yulia N. Kocharovskaya, Alexander G. Bogun, Ivan V. Gmoshinski, Sergey A. Khotimchenko and Dmitry B. Nikityuk
Nanomaterials 2024, 14(9), 768; https://doi.org/10.3390/nano14090768 - 26 Apr 2024
Cited by 2 | Viewed by 1921
Abstract
Bacterial nanocellulose (BNC) is being considered as a potential replacement for microcrystalline cellulose as a food additive and a source of dietary fiber due to its unique properties. However, studies on the risks of consuming BNC in food are limited, and it is [...] Read more.
Bacterial nanocellulose (BNC) is being considered as a potential replacement for microcrystalline cellulose as a food additive and a source of dietary fiber due to its unique properties. However, studies on the risks of consuming BNC in food are limited, and it is not yet approved for use in food in the US, EU, and Russia. Aim: This study aims to perform a toxicological and hygienic assessment of the safety of BNC in a subacute 8-week administration in rats. Methods: BNC was administered to male Wistar rats in doses of 0, 1.0, 10.0, and 100 mg/kg body weight for 8 weeks. Various parameters such as anxiety levels, cognitive function, organ masses, blood serum and liver biochemistry, oxidative stress markers, vitamin levels, antioxidant gene expression, and liver and kidney histology were evaluated. Results: Low and medium doses of BNC increased anxiety levels and liver glutathione, while high doses led to elevated LDL cholesterol, creatinine, and uric acid levels. Liver tissue showed signs of degeneration at high doses. BNC did not significantly affect vitamin levels. Conclusion: The adverse effects of BNC are either not dose-dependent or fall within normal physiological ranges. Any effects on rats are likely due to micronutrient deficiencies or impacts on intestinal microbiota. Full article
(This article belongs to the Special Issue Nanosafety and Nanotoxicology: Current Opportunities and Challenges)
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