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New Approach Methodologies in Particle and Fibre Toxicology
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New Approach Methodologies in Particle and Fibre Toxicology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (30 July 2023) | Viewed by 12067

Special Issue Editor

Dr. Carsten Weiss

E-Mail Website
Guest Editor
Institute of Biological and Chemical Systems–Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology (KIT), Hermann‐von‐Helmholtz‐Platz 1, 76344 Eggenstein‐Leopoldshafen, Germany
Interests: nanotoxicology; nanomedicine; molecular toxicology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The toxicity of particulate matter (PM) has gained particular attention since decades, as exposure to it, for example, in ambient air or at the workplace, has been linked to human diseases. Recent topics in the field of particle and fibre toxicology include the hazard profiling of advanced materials, including nanomaterials, and of micro- and nanoplastics. Potential adverse effects of such materials in humans upon inhalation, ingestion or dermal contact require thorough investigation. As the hazard assessment of chemicals by standard regulatory testing most often relies on animal experiments, there are ongoing efforts to reduce, refine or even replace (three Rs) in vivo studies by new approach methodologies (NAMs). With the advent of novel cellular models and approaches such as coculture systems, air–liquid interface (ALI) exposure, organ-on-a-chip models or the availability of primary and stem cells, just to name a few, it is possible to better mimic the physiological conditions and assess the biological impact of chemicals in general, but also particles and fibres in particular. Additionally, techniques concerning dosimetry, the quantification of the dose of applied materials in the various compartments during exposure, need to be further developed. Therefore, the establishment of NAMs requires ongoing interdisciplinary research across different fields, such as toxicology, chemistry, biology as well as engineering and physics to further improve next-generation risk assessment.

This Special Issue aims to cover research in the field of particle and fibre toxicology with special emphasis on NAMs and the molecular mechanism of action. The submission of reviews, original research articles and communications is welcome.

Dr. Carsten Weiss
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • particulate matter
  • advanced materials
  • nanomaterials
  • in vitro models, three R principle
  • hazard assessment

Published Papers (6 papers)

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Research

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25 pages, 3233 KiB  
Article
Comparing the Toxicological Responses of Pulmonary Air–Liquid Interface Models upon Exposure to Differentially Treated Carbon Fibers
by Alexandra Friesen, Susanne Fritsch-Decker, Sonja Mülhopt, Caroline Quarz, Jonathan Mahl, Werner Baumann, Manuela Hauser, Manuela Wexler, Christoph Schlager, Bastian Gutmann, Tobias Krebs, Ann-Kathrin Goßmann, Frederik Weis, Matthias Hufnagel, Dieter Stapf, Andrea Hartwig and Carsten Weiss
Int. J. Mol. Sci. 2023, 24(3), 1927; https://doi.org/10.3390/ijms24031927 - 18 Jan 2023
Cited by 3 | Viewed by 1950
Abstract
In recent years, the use of carbon fibers (CFs) in various sectors of industry has been increasing. Despite the similarity of CF degradation products to other toxicologically relevant materials such as asbestos fibers and carbon nanotubes, a detailed toxicological evaluation of this class [...] Read more.
In recent years, the use of carbon fibers (CFs) in various sectors of industry has been increasing. Despite the similarity of CF degradation products to other toxicologically relevant materials such as asbestos fibers and carbon nanotubes, a detailed toxicological evaluation of this class of material has yet to be performed. In this work, we exposed advanced air–liquid interface cell culture models of the human lung to CF. To simulate different stresses applied to CF throughout their life cycle, they were either mechanically (mCF) or thermo-mechanically pre-treated (tmCF). Different aspects of inhalation toxicity as well as their possible time-dependency were monitored. mCFs were found to induce a moderate inflammatory response, whereas tmCF elicited stronger inflammatory as well as apoptotic effects. Furthermore, thermal treatment changed the surface properties of the CF resulting in a presumed adhesion of the cells to the fiber fragments and subsequent cell loss. Triple-cultures encompassing epithelial, macrophage, and fibroblast cells stood out with an exceptionally high inflammatory response. Only a weak genotoxic effect was detected in the form of DNA strand breaks in mono- and co-cultures, with triple-cultures presenting a possible secondary genotoxicity. This work establishes CF fragments as a potentially harmful material and emphasizes the necessity of further toxicological assessment of existing and upcoming advanced CF-containing materials. Full article
(This article belongs to the Special Issue New Approach Methodologies in Particle and Fibre Toxicology)
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22 pages, 7656 KiB  
Article
Gene Expression Profiling of Mono- and Co-Culture Models of the Respiratory Tract Exposed to Crystalline Quartz under Submerged and Air-Liquid Interface Conditions
by Alexandra Friesen, Susanne Fritsch-Decker, Matthias Hufnagel, Sonja Mülhopt, Dieter Stapf, Carsten Weiss and Andrea Hartwig
Int. J. Mol. Sci. 2022, 23(14), 7773; https://doi.org/10.3390/ijms23147773 - 14 Jul 2022
Cited by 6 | Viewed by 2279
Abstract
In vitro lung cell models like air-liquid interface (ALI) and 3D cell cultures have advanced greatly in recent years, being especially valuable for testing advanced materials (e.g., nanomaterials, fibrous substances) when considering inhalative exposure. Within this study, we established submerged and ALI cell [...] Read more.
In vitro lung cell models like air-liquid interface (ALI) and 3D cell cultures have advanced greatly in recent years, being especially valuable for testing advanced materials (e.g., nanomaterials, fibrous substances) when considering inhalative exposure. Within this study, we established submerged and ALI cell culture models utilizing A549 cells as mono-cultures and co-cultures with differentiated THP-1 (dTHP-1), as well as mono-cultures of dTHP-1. After ALI and submerged exposures towards α-quartz particles (Min-U-Sil5), with depositions ranging from 15 to 60 µg/cm2, comparison was made with respect to their transcriptional cellular responses employing high-throughput RT-qPCR. A significant dose- and time-dependent induction of genes coding for inflammatory proteins, e.g., IL-1A, IL-1B, IL-6, IL-8, and CCL22, as well as genes associated with oxidative stress response such as SOD2, was observed, even more pronounced in co-cultures. Changes in the expression of similar genes were more pronounced under submerged conditions when compared to ALI exposure in the case of A549 mono-cultures. Hereby, the activation of the NF-κB signaling pathway and the NLRP3 inflammasome seem to play an important role. Regarding genotoxicity, neither DNA strand breaks in ALI cultivated cells nor a transcriptional response to DNA damage were observed. Altogether, the toxicological responses depended considerably on the cell culture model and exposure scenario, relevant to be considered to improve toxicological risk assessment. Full article
(This article belongs to the Special Issue New Approach Methodologies in Particle and Fibre Toxicology)
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18 pages, 2633 KiB  
Article
Comparing α-Quartz-Induced Cytotoxicity and Interleukin-8 Release in Pulmonary Mono- and Co-Cultures Exposed under Submerged and Air-Liquid Interface Conditions
by Alexandra Friesen, Susanne Fritsch-Decker, Matthias Hufnagel, Sonja Mülhopt, Dieter Stapf, Andrea Hartwig and Carsten Weiss
Int. J. Mol. Sci. 2022, 23(12), 6412; https://doi.org/10.3390/ijms23126412 - 8 Jun 2022
Cited by 9 | Viewed by 1960
Abstract
The occupational exposure to particles such as crystalline quartz and its impact on the respiratory tract have been studied extensively in recent years. For hazard assessment, the development of physiologically more relevant in-vitro models, i.e., air-liquid interface (ALI) cell cultures, has greatly progressed. [...] Read more.
The occupational exposure to particles such as crystalline quartz and its impact on the respiratory tract have been studied extensively in recent years. For hazard assessment, the development of physiologically more relevant in-vitro models, i.e., air-liquid interface (ALI) cell cultures, has greatly progressed. Within this study, pulmonary culture models employing A549 and differentiated THP-1 cells as mono-and co-cultures were investigated. The different cultures were exposed to α-quartz particles (Min-U-Sil5) with doses ranging from 15 to 66 µg/cm2 under submerged and ALI conditions and cytotoxicity as well as cytokine release were analyzed. No cytotoxicity was observed after ALI exposure. Contrarily, Min-U-Sil5 was cytotoxic at the highest dose in both submerged mono- and co-cultures. A concentration-dependent release of interleukin-8 was shown for both exposure types, which was overall stronger in co-cultures. Our findings showed considerable differences in the toxicological responses between ALI and submerged exposure and between mono- and co-cultures. A substantial influence of the presence or absence of serum in cell culture media was noted as well. Within this study, the submerged culture was revealed to be more sensitive. This shows the importance of considering different culture and exposure models and highlights the relevance of communication between different cell types for toxicological investigations. Full article
(This article belongs to the Special Issue New Approach Methodologies in Particle and Fibre Toxicology)
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Review

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39 pages, 7747 KiB  
Review
Physico-Chemical Approaches to Investigate Surface Hydroxyls as Determinants of Molecular Initiating Events in Oxide Particle Toxicity
by Cristina Pavan, Rosangela Santalucia, Guillermo Escolano-Casado, Piero Ugliengo, Lorenzo Mino and Francesco Turci
Int. J. Mol. Sci. 2023, 24(14), 11482; https://doi.org/10.3390/ijms241411482 - 14 Jul 2023
Cited by 5 | Viewed by 1275
Abstract
The study of molecular recognition patterns is crucial for understanding the interactions between inorganic (nano)particles and biomolecules. In this review we focus on hydroxyls (OH) exposed at the surface of oxide particles (OxPs) which can play a key role in molecular initiating events [...] Read more.
The study of molecular recognition patterns is crucial for understanding the interactions between inorganic (nano)particles and biomolecules. In this review we focus on hydroxyls (OH) exposed at the surface of oxide particles (OxPs) which can play a key role in molecular initiating events leading to OxPs toxicity. We discuss here the main analytical methods available to characterize surface OH from a quantitative and qualitative point of view, covering thermogravimetry, titration, ζ potential measurements, and spectroscopic approaches (NMR, XPS). The importance of modelling techniques (MD, DFT) for an atomistic description of the interactions between membranes/proteins and OxPs surfaces is also discussed. From this background, we distilled a new approach methodology (NAM) based on the combination of IR spectroscopy and bioanalytical assays to investigate the molecular interactions of OxPs with biomolecules and membranes. This NAM has been already successfully applied to SiO2 particles to identify the OH patterns responsible for the OxPs’ toxicity and can be conceivably extended to other surface-hydroxylated oxides. Full article
(This article belongs to the Special Issue New Approach Methodologies in Particle and Fibre Toxicology)
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11 pages, 1231 KiB  
Review
Exposome, Molecular Pathways and One Health: The Invertebrate Caenorhabditis elegans
by Anna von Mikecz
Int. J. Mol. Sci. 2022, 23(16), 9084; https://doi.org/10.3390/ijms23169084 - 13 Aug 2022
Cited by 4 | Viewed by 1801
Abstract
Due to its preferred habitats in the environment, the free-living nematode Caenorhabditis elegans has become a realistic target organism for pollutants, including manufactured nanoparticles. In the laboratory, the invertebrate animal model represents a cost-effective tool to investigate the molecular mechanisms of the biological [...] Read more.
Due to its preferred habitats in the environment, the free-living nematode Caenorhabditis elegans has become a realistic target organism for pollutants, including manufactured nanoparticles. In the laboratory, the invertebrate animal model represents a cost-effective tool to investigate the molecular mechanisms of the biological response to nanomaterials. With an estimated number of 22,000 coding genes and short life span of 2–3 weeks, the small worm is a giant when it comes to characterization of molecular pathways, long-term low dose pollutant effects and vulnerable age-groups. Here, we review (i) flows of manufactured nanomaterials and exposition of C. elegans in the environment, (ii) the track record of C. elegans in biomedical research, and (iii) its potential to contribute to the investigation of the exposome and bridge nanotoxicology between higher organisms, including humans. The role of C. elegans in the one health concept is taken one step further by proposing methods to sample wild nematodes and their molecular characterization by single worm proteomics. Full article
(This article belongs to the Special Issue New Approach Methodologies in Particle and Fibre Toxicology)
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Other

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12 pages, 1653 KiB  
Perspective
Lung Organoids for Hazard Assessment of Nanomaterials
by Miriam T. Kastlmeier, Eva M. Guenther, Tobias Stoeger and Carola Voss
Int. J. Mol. Sci. 2022, 23(24), 15666; https://doi.org/10.3390/ijms232415666 - 10 Dec 2022
Cited by 5 | Viewed by 2019
Abstract
Lung epithelial organoids for the hazard assessment of inhaled nanomaterials offer a promising improvement to in vitro culture systems used so far. Organoids grow in three-dimensional (3D) spheres and can be derived from either induced pluripotent stem cells (iPSC) or primary lung tissue [...] Read more.
Lung epithelial organoids for the hazard assessment of inhaled nanomaterials offer a promising improvement to in vitro culture systems used so far. Organoids grow in three-dimensional (3D) spheres and can be derived from either induced pluripotent stem cells (iPSC) or primary lung tissue stem cells from either human or mouse. In this perspective we will highlight advantages and disadvantages of traditional culture systems frequently used for testing nanomaterials and compare them to lung epithelial organoids. We also discuss the differences between tissue and iPSC-derived organoids and give an outlook in which direction the whole field could possibly go with these versatile tools. Full article
(This article belongs to the Special Issue New Approach Methodologies in Particle and Fibre Toxicology)
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