Adverse Outcome Pathway Development for Assessment of Lung Carcinogenicity by Nanoparticles

Frontiers in Toxicology, Journal Year: 2021, Volume and Issue: 3

Published: April 29, 2021

Lung cancer, one of the most common and deadly forms is in some cases associated with exposure to certain types particles. With rise nanotechnology, there concern that engineered nanoparticles may be among such In absence epidemiological evidence, assessment nanoparticle carcinogenicity currently performed on a time-consuming case-by-case basis, relying mainly animal experiments. Non-animal alternatives exist, including few validated cell-based methods accepted for regulatory risk nanoparticles. Furthermore, new approach methodologies (NAMs), focused carcinogenic mechanisms capable handling increasing numbers nanoparticles, have been developed. However, alternative are applied as weight-of-evidence linked generally required data, since challenges remain regarding interpretation results. These more easily overcome by novel Adverse Outcome Pathway (AOP) framework, which provides basis validation uptake mechanism-focused assessment. Here, we propose an AOP lung cancer induced nanosized foreign matter, anchored selection 18 standardized NAMs silico - vitro -based integrated carcinogenicity. The potential further refinement its components discussed relation available nanosafety knowledge data. Overall, this perspective development AOP-aligned methods-based testing strategies nanoparticle-induced cancer.

Language: Английский

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Genotoxicity testing of nanomaterials

Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology, Journal Year: 2022, Volume and Issue: 14(6)

Published: Nov. 1, 2022

Abstract Nanomaterials have outstanding and unprecedented advantageous material properties but may also cause adverse effects in humans upon exposure. Testing nanomaterials for genotoxic is challenging because traditional testing methods were designed small, soluble molecules not be easily applicable without modifications. This review critically examines available genotoxicity tests use with nanomaterials, including DNA damage such as the comet assay, gene mutation mouse lymphoma hprt chromosome micronucleus test aberration test. It presents arguments relative usefulness of various tests, preferring over scoring mutations mammalian cell Ames has limited utility. Finally, it points out open questions further needs adapting validation, reference selection top concentrations, well relevance applicability systems need to define strategies. article categorized under: Toxicology Regulatory Issues Nanomedicine > Policy

Language: Английский

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Nanosafety: An Evolving Concept to Bring the Safest Possible Nanomaterials to Society and Environment

Nanomaterials, Journal Year: 2022, Volume and Issue: 12(11), P. 1810 - 1810

Published: May 25, 2022

The use of nanomaterials has been increasing in recent times, and they are widely used industries such as cosmetics, drugs, food, water treatment, agriculture. rapid development new demands a set approaches to evaluate the potential toxicity risks related them. In this regard, nanosafety using adapting already existing methods (toxicological approach), but unique characteristics demand (nanotoxicology) fully understand toxicity, immunotoxicity, (epi)genotoxicity. addition, technologies, organs-on-chips sophisticated sensors, under and/or adaptation. All information generated is develop silico trying predict effects newly developed materials. overall evaluation from their production final disposal chain completed life cycle assessment (LCA), which becoming an important element considering sustainability environmental impact. review, we give overview all these elements nanosafety.

Language: Английский

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

Particle and Fibre Toxicology, Journal Year: 2022, Volume and Issue: 19(1)

Published: March 16, 2022

Cellulose nanofibrils (CNFs) have emerged as a sustainable and environmentally friendly option for broad range of applications. The fibrous nature high biopersistence CNFs call thorough toxicity assessment, but it is presently unclear which physico-chemical properties could play role in determining the potential toxic response to CNF. Here, we assessed whether surface composition size modulate genotoxicity human bronchial epithelial BEAS-2B cells. We examined three fractions (fine, medium coarse) four with different chemistry: unmodified (U-CNF) functionalized 2,2,6,6-tetramethyl-piperidin-1-oxyl (TEMPO) (T-CNF), carboxymethyl (C-CNF) epoxypropyltrimethylammonium chloride (EPTMAC) (E-CNF). In addition, source fibre was also evaluated non-nanosized material.

Language: Английский

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DNA Oxidative Damage as a Sensitive Genetic Endpoint to Detect the Genotoxicity Induced by Titanium Dioxide Nanoparticles

Nanomaterials, Journal Year: 2022, Volume and Issue: 12(15), P. 2616 - 2616

Published: July 29, 2022

The genotoxicity of nanomaterials has attracted great attention in recent years. As a possible occupational carcinogen, the genotoxic effects and underlying mechanisms titanium dioxide nanoparticles (TiO2 NPs) have been particular concern. In this study, effect TiO2 NPs (0, 25, 50 100 µg/mL) on DNA damage role oxidative stress were investigated using human bronchial epithelial cells (BEAS-2B) as an vitro model. After detailed characterization, cytotoxicity was detected. Through transmission electron microscopy (TEM), we found that entered cytoplasm but did not penetrate deep into nucleus cells. intracellular levels reactive oxygen species (ROS) significantly increased dose-dependent manner ratios GSH/GSSG also decreased. results normal comet assay negative, while Fpg-modified specifically detected positive. Meanwhile, N-acetyl-L-cysteine (NAC) intervention inhibited induced by NPs. Therefore, it suggested could induce cytotoxicity, BEAS-2B may be more sensitive genetic endpoint to detect

Language: Английский

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Review of New Approach Methodologies for Application in Risk Assessment of Nanoparticles in the Food and Feed Sector: Status and Challenges

EFSA Supporting Publications, Journal Year: 2024, Volume and Issue: 21(9)

Published: Sept. 1, 2024

Abstract New Approach Methodologies (NAMs), broadly understood to include in silico, chemico, vitro and ex vivo methods, show great potential advancing risk assessment albeit their regulatory implementation is lagging. The EFSA Guidance on of nanomaterials (EFSA Nano‐RA) suggests nano‐specific best achieved through Integrated Approaches Testing Assessment (IATAs) with NAMs as the first choice generate new information. Integrating promises several advantages such a better human focus, more detailed insights into molecular mechanisms higher efficacy. However, applying NMs also poses considerable challenges issues related dispersion stability, dosimetry, agglomeration, dissolution, transformations or assay interferences. Significant efforts are being undertaken by standardisation organisations research projects establish various for NMs. Here thorough review provided covering that will be potentially useful food feed sector. It follows structure Nano‐RA expands it, where needed, support decision‐making selection NM assessment. begins an overview NAM‐frameworks, followed description individual including those relevant physicochemical characterisation, exposure hazard toxicodynamics toxicokinetics. focus concerning degradation/dissolution, genotoxicity, cytotoxicity, oxidative stress, (pro‐)inflammation, barrier integrity important endpoints initial screening according framework. As result, total 267 nano‐relevant NAMs, mostly “not validated” (with few notable exceptions), were included this review. Validation notwithstanding, could already prove reliable NMs, especially integrated approaches.

Language: Английский

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Mechanisms and Assessment of Genotoxicity of Metallic Engineered Nanomaterials in the Human Environment

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2401 - 2401

Published: Oct. 20, 2024

Engineered nanomaterials (ENMs) have a broad array of applications in agriculture, engineering, manufacturing, and medicine. Decades toxicology research demonstrated that ENMs can cause genotoxic effects on bacteria, mammalian cells, animals. Some metallic (MENMs), e.g., metal or oxide nanoparticles TiO

Language: Английский

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New Approach Methods (NAMs) for Genotoxicity Assessment of Nano- and Advanced Materials; Advantages and Challenges

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Journal Year: 2025, Volume and Issue: unknown, P. 503867 - 503867

Published: March 1, 2025

Language: Английский

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Genotoxicity of Graphene-Based Materials

Nanomaterials, Journal Year: 2022, Volume and Issue: 12(11), P. 1795 - 1795

Published: May 24, 2022

Graphene-based materials (GBMs) are a broad family of novel carbon-based nanomaterials with many nanotechnology applications. The increasing market GBMs raises concerns on their possible impact human health. Here, we review the existing literature genotoxic potential over last ten years. A total 50 articles including in vitro, vivo, silico, and biomonitoring studies were selected. Graphene oxides most analyzed materials, followed by reduced graphene oxides. Most evaluations performed vitro using comet assay (detecting DNA damage). micronucleus chromosome damage) was used validated assay, whereas only two publications reported results mammalian gene mutations. same material rarely assessed more than one assay. Despite inhalation being main exposure route occupational settings, vivo study intratracheal instillation, another data. Based studies, some have to induce genetic damage, although type damage depends material. variability GBMs, cellular systems methods precludes identification physico-chemical properties that could drive genotoxicity response GBMs.

Language: Английский

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A systematic quality evaluation and review of nanomaterial genotoxicity studies: a regulatory perspective

Particle and Fibre Toxicology, Journal Year: 2022, Volume and Issue: 19(1)

Published: Sept. 14, 2022

Abstract The number of publications in the field nanogenotoxicology and amount genotoxicity data on nanomaterials (NMs) several databases generated by European Union (EU) funded projects have increased during last decade. In parallel, large research efforts contributed to both our understanding key physico-chemical (PC) parameters regarding NM characterization as well limitations toxicological assays originally designed for soluble chemicals. Hence, it is becoming increasingly clear that not all these are reliable or relevant from regulatory perspective. aim this systematic review investigate extent studies NMs can be considered current standards bring focus what needed a study useful point view. Due vast available, we chose limit search two groups, which raised substantial interest recent years: nanofibers (including nanotubes) metal-containing nanoparticles . Focusing peer-reviewed publications, evaluated completeness PC tested NMs, documentation model system, design, results according quality assessment approach developed EU FP-7 GUIDEnano project. Further, building recently published recommendations best practices research, created set criteria address assay-specific reliability relevance risk purposes. Articles were then reviewed, qualifying discussed, most common shortcomings highlighted. Moreover, under FP7 H2020 framework collectively feed information they produced into eNanoMapper database. As result, over years, database has been extended with various depending existing knowledge at time entry. These activities highly since negative often published. Here, reviewed NanoInformaTIX instance database, hosts nine initiatives. We feasibility use perspective each experimental

Language: Английский

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