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Toxics
Special Issues
Feature Papers in the Novel Methods in Toxicology Research
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Feature Papers in the Novel Methods in Toxicology Research

A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Novel Methods in Toxicology Research".

Deadline for manuscript submissions: 31 October 2024 | Viewed by 1886

Special Issue Editor

Dr. Natalia Garcia-Reyero

E-Mail Website
Guest Editor
Institute for Genomics, Biocomputing & Biotechnology, Mississippi State University, Starkville, MS 39759, USA
Interests: toxicogenomics; predictive toxicology; zebrafish; adverse outcome pathways
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue encourages innovative, multidisciplinary research in the field of predictive toxicology, with a focus on promoting the use of New Approach Methodologies (NAMs) to predict hazards. This series of articles will aim to enhance innovative human and environmental health-based approaches that will allow progress towards more predictive hazard assessments while embracing replacement, reduction, and refinement. This Special Issue welcomes original research articles as well as reviews and short communications related to any aspect of NAMs, including (but not limited to) in vitro, in silico, and computational and AI approaches, as well as gaps, challenges, and regulatory acceptance. 

Dr. Natalia Garcia-Reyero
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. Toxics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • NAMS
  • in vitro
  • in silico
  • AI
  • regulatory acceptance
  • predictive toxicology
  • high throughput

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Further information on MDPI's Special Issue polices can be found here.

Published Papers (3 papers)

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Research

17 pages, 3344 KiB  
Article
A High-Throughput Method for Quantifying Drosophila Fecundity
by Andreana Gomez, Sergio Gonzalez, Ashwini Oke, Jiayu Luo, Johnny B. Duong, Raymond M. Esquerra, Thomas Zimmerman, Sara Capponi, Jennifer C. Fung and Todd G. Nystul
Toxics 2024, 12(9), 658; https://doi.org/10.3390/toxics12090658 - 9 Sep 2024
Viewed by 350
Abstract
The fruit fly, Drosophila melanogaster, is an experimentally tractable model system that has recently emerged as a powerful “new approach methodology” (NAM) for chemical safety testing. As oogenesis is well conserved at the molecular and cellular level, measurements of Drosophila fecundity can [...] Read more.
The fruit fly, Drosophila melanogaster, is an experimentally tractable model system that has recently emerged as a powerful “new approach methodology” (NAM) for chemical safety testing. As oogenesis is well conserved at the molecular and cellular level, measurements of Drosophila fecundity can be useful for identifying chemicals that affect reproductive health across species. However, standard Drosophila fecundity assays have been difficult to perform in a high-throughput manner because experimental factors such as the physiological state of the flies and environmental cues must be carefully controlled to achieve consistent results. In addition, exposing flies to a large number of different experimental conditions (such as chemical additives in the diet) and manually counting the number of eggs laid to determine the impact on fecundity is time-consuming. We have overcome these challenges by combining a new multiwell fly culture strategy with a novel 3D-printed fly transfer device to rapidly and accurately transfer flies from one plate to another, the RoboCam, a low-cost, custom-built robotic camera to capture images of the wells automatically, and an image segmentation pipeline to automatically identify and quantify eggs. We show that this method is compatible with robust and consistent egg laying throughout the assay period and demonstrate that the automated pipeline for quantifying fecundity is very accurate (r2 = 0.98 for the correlation between the automated egg counts and the ground truth). In addition, we show that this method can be used to efficiently detect the effects on fecundity induced by dietary exposure to chemicals. Taken together, this strategy substantially increases the efficiency and reproducibility of high-throughput egg-laying assays that require exposing flies to multiple different media conditions. Full article
(This article belongs to the Special Issue Feature Papers in the Novel Methods in Toxicology Research)
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20 pages, 23124 KiB  
Article
Assessing Receptor Activation in 2D and 3D Cultured Hepatocytes: Responses to a Single Compound and a Complex Mixture
by Laiba Jamshed, Shanza Jamshed, Richard A. Frank, L. Mark Hewitt, Philippe J. Thomas and Alison C. Holloway
Toxics 2024, 12(9), 631; https://doi.org/10.3390/toxics12090631 - 28 Aug 2024
Viewed by 446
Abstract
Responding to global standards and legislative updates in Canada, including Bill S-5 (2023), toxicity testing is shifting towards more ethical, in vitro methods. Traditional two-dimensional (2D) monolayer cell cultures, limited in replicating the complex in vivo environment, have prompted the development of more [...] Read more.
Responding to global standards and legislative updates in Canada, including Bill S-5 (2023), toxicity testing is shifting towards more ethical, in vitro methods. Traditional two-dimensional (2D) monolayer cell cultures, limited in replicating the complex in vivo environment, have prompted the development of more relevant three-dimensional (3D) spheroidal hepatocyte cultures. This study introduces the first 3D spheroid model for McA-RH7777 cells, assessing xenobiotic receptor activation, cellular signaling, and toxicity against dexamethasone and naphthenic acid (NA)-fraction components; NAFCs. Our findings reveal that 3D McA-RH7777 spheroids demonstrate enhanced sensitivity and more uniform dose–response patterns in gene expression related to xenobiotic metabolism (AhR and PPAR) for both single compounds and complex mixtures. Specifically, 3D cultures showed significant gene expression changes upon dexamethasone exposure and exhibited varying degrees of sensitivity and resistance to the apoptotic effects induced by NAFCs, in comparison to 2D cultures. The optimization of 3D culture conditions enhances the model’s physiological relevance and enables the identification of genomic signatures under varied exposures. This study highlights the potential of 3D spheroid cultures in providing a more accurate representation of the liver’s microenvironment and advancing our understanding of cellular mechanisms in toxicity testing. Full article
(This article belongs to the Special Issue Feature Papers in the Novel Methods in Toxicology Research)
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13 pages, 4224 KiB  
Article
Evaluation of THP-1 and Jurkat Cell Lines Coculture for the In Vitro Assessment of the Effects of Immunosuppressive Substances
by Nina Franko and Marija Sollner Dolenc
Toxics 2024, 12(8), 607; https://doi.org/10.3390/toxics12080607 - 19 Aug 2024
Viewed by 496
Abstract
The strong appeal to reduce animal testing calls for the development and validation of in vitro, in chemico and in silico models that would replace the need for in vivo testing and ex vivo materials. A category that requires such new approach methods [...] Read more.
The strong appeal to reduce animal testing calls for the development and validation of in vitro, in chemico and in silico models that would replace the need for in vivo testing and ex vivo materials. A category that requires such new approach methods is the assessment of immunosuppression that can be induced by chemicals including environmental pollutants. To assess the immunosuppressive action on monocytes and lymphocytes, we mimicked the whole-blood cytokine-release assay by preparing an in vitro coculture of THP-1 and Jurkat cell lines. We optimised its activation and investigated the effects of known immunosuppressive drugs with different mechanisms of action on the release of proinflammatory cytokines. Decreased secretion of IL-8 was achieved by several immunosuppressive mechanisms and was therefore selected as an appropriate marker of immunosuppression. A set of environmentally occurring bisphenols, BPA, BPAP, BPP, BPZ, BPE, TCBPA and BPS-MAE, were then applied to the model and BPP and BPZ were found to act as potent immunosuppressants at micromolar concentrations. Full article
(This article belongs to the Special Issue Feature Papers in the Novel Methods in Toxicology Research)
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