Article
Cell Biology
Joost Boeckmans, Alexandra Gatzios, Anja Heymans, Matthias Rombaut, Vera Rogiers, Joery De Kock, Tamara Vanhaecke, Robim M. Rodrigues
Summary: This study characterized the transcriptome of various in vitro models of non-alcoholic steatohepatitis (NASH) and investigated the effects of the potential anti-NASH compound elafibranor on these models. The study found common anti-inflammatory responses in both elafibranor-treated in vitro models and clinical datasets of NAFLD patients after bariatric surgery. However, there were discordant modulations of key factors in lipid metabolism, suggesting the need for further investigation of elafibranor as a potential NASH therapy.
Article
Pharmacology & Pharmacy
Mieke Van Mulders, Nancy Liodo Missigba, Birgit Mertens, Vera Rogiers
Summary: New Approach Methodologies (NAMs), such as computer modeling, high throughput testing, omics, and sophisticated cell cultures, can reduce or eliminate the use of experimental animals in life sciences. The RE-Place project in Belgium serves as an example of local initiatives creating a central database of available NAMs and connecting experts and research centers. The online tool and open access database contribute to building trust in NAMs and encouraging their use and regulatory acceptance.
FRONTIERS IN PHARMACOLOGY
(2022)
Editorial Material
Medicine, Research & Experimental
Helena Kandarova
ATLA-ALTERNATIVES TO LABORATORY ANIMALS
(2022)
Article
Medicine, Legal
Quinten Marcelis, Alexandra Gatzios, Eric Deconinck, Vera Rogiers, Bart Desmedt, Tamara Vanhaecke
Summary: Allergic contact dermatitis is common in Western countries due to the use of perfumed products. Women using scented menstrual hygiene products may be at risk of sensitization and developing ACD, as allergens can easily penetrate the vaginal mucosa. Quantitative risk assessment of four sensitizing chemicals found in scented MHPs revealed that one tampon leached a potentially sensitizing substance. Labeling of allergens on scented MHPs would help prevent adverse effects.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2022)
Editorial Material
Toxicology
Joost Boeckmans, Alexandra Gatzios, Joern M. Schattenberg, Robim M. Rodrigues, Vera Rogiers, Tamara Vanhaecke
ARCHIVES OF TOXICOLOGY
(2023)
Article
Medicine, Legal
Corrado L. Galli, Ulrike Bernauer, Laurent Bodin, Qasim Chaudhry, Pieter Jan Coenraads, Maria Dusinska, Janine Ezendam, Berit Granum, Eric Gaffet, Eirini Panteri, Vera Rogiers, Christophe Rousselle, Maciej Stepnik, Tamara Vanhaecke, Susan Wijnhoven, Aglaia Koutsodimou, Wolfgang Uter, Natalie von Goetz
Summary: SCCS has issued opinions on Acid Yellow 3 - C054 on May 7th and July 23rd, 2021.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2023)
Article
Toxicology
Quinten Marcelis, Eric Deconinck, Vera Rogiers, Tamara Vanhaecke, Bart Desmedt
Summary: The in chemico direct peptide reactivity assay (DPRA) is validated for assessing protein reactivity, specifically in skin sensitization induction. The assay is applicable to test multi-constituent substances and mixtures of known composition, but caution should be taken when deviating from the recommended testing concentration. The DPRA was able to distinguish skin sensitizers in binary mixtures, but its applicability for mixtures of unknown composition is limited.
ARCHIVES OF TOXICOLOGY
(2023)
Review
Environmental Sciences
Sebastian Schmeisser, Andrea Miccoli, Martin von Bergen, Elisabet Berggren, Albert Braeuning, Wibke Busch, Christian Desaintes, Anne Gourmelon, Roland Grafstrom, Joshua Harrill, Thomas Hartung, Matthias Herzler, George E. N. Kass, Nicole Kleinstreuer, Marcel Leist, Mirjam Luijten, Philip Marx-Stoelting, Oliver Poetz, Bennard van Ravenzwaay, Rob Roggeband, Vera Rogiers, Adrian Roth, Pascal Sanders, Russell S. Thomas, Anne Marie Vinggaard, Mathieu Vinken, Bob van de Water, Andreas Luch, Tewes Tralau
Summary: The animal-centric approach of chemical safety assessment is under pressure, and there is a growing demand for a paradigm shift due to concerns about overall performance, sustainability, relevance for human health risk assessment, and ethics. New Approach Methodologies (NAMs), including various methods such as QSAR predictions, HTS bioassays, omics applications, cell cultures, organoids, MPS, machine learning models, and AI, have the potential to revolutionize regulatory risk assessment by providing more human-relevant decision-making. However, challenges such as addressing chronic toxicity, stakeholder hesitance, predictivity, reproducibility, and adapting regulatory frameworks need to be overcome for the broader application of NAMs. This conceptual perspective is based on the findings and conclusions of a symposium and workshop held in Berlin in November 2021 and aims to shed light on the gradual integration of NAMs into chemical risk assessment for the protection of human health, leading to an animal-free Next Generation Risk Assessment (NGRA).
ENVIRONMENT INTERNATIONAL
(2023)
Article
Pharmacology & Pharmacy
Karolien Buyl, Martine Vrints, Ruani Fernando, Terry Desmae, Thomas Van Eeckhoutte, Mia Jans, Jan Van Der Schueren, Joost Boeckmans, Robim M. Rodrigues, Veerle De Boe, Vera Rogiers, Joery De Kock, Filip Beirinckx, Tamara Vanhaecke
Summary: This study introduces a novel in vitro human liver cell model for studying metabolic dysfunction-associated steatotic liver disease. The model accurately simulates the insulin-driven pathway of fatty acid synthesis and allows for high-throughput screening of potential therapeutic drugs.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Simone Bonazzi, Audrey Gray, Noel M. Thomsen, Jonathan Biag, Nancy Labbe-Giguere, Erin P. Keaney, Hasnain A. Malik, Yingchuan Sun, Jill Nunez, Rajeshri G. Karki, Mark Knapp, Robert Elling, John Fuller, Gwynn Pardee, Lucas Craig, Ketthsy Capre, Sarah Salas, Aakruti Gorde, Guiqing Liang, Danuta Lubicka, Stephanie M. McTighe, Carleton Goold, Shanming Liu, Lin Deng, Jin Hong, Alexander Fekete, Pascal Stadelmann, Wilfried Frieauff, Azeddine Elhajouji, Daniel Bauer, Andreas Lerchner, Branko Radetich, Pascal Furet, Grazia Piizzi, Doug Burdette, Christopher J. Wilson, Stefan Peukert, Lawrence G. Hamann, Leon O. Murphy, Daniel Curtis
Summary: The allosteric inhibitor everolimus reduces seizures in TSC patients by partially inhibiting mTOR functions. However, it has limited brain permeability, so a catalytic mTOR inhibitor optimized for CNS indications was developed. Compound 1 showed genotoxicity risk, but compounds 9 and 11 without genotoxicity risk successfully corrected aberrant mTOR activity and improved the survival rate in the Tsc1 gene knockout model. Unfortunately, compounds 9 and 11 had limited oral exposures and dose-limiting toxicities in cynomolgus macaque, but they remain useful for studying mTOR hyperactivity in CNS disease models.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Legal
Mark T. D. Cronin, Nicholas Ball, Sonja Beken, Hans Bender, Ofelia Bercaru, Laura Caneva, Marco Corvaro, Richard A. Currie, Jeffrey L. Dawson, Paul Desert, Sylvia E. Escher, Antonio Franco, Amaia Irizar, Jyotigna M. Mehta, Vera Rogiers, Raphae T. Tremblay, Carl Westmoreland, Gavin Maxwell
Summary: Understanding and estimating exposure to substances is crucial for safe manufacture and use. The European Partnership for Alternative Approaches to Animal Testing (EPAA) held a Partners' Forum (PF) to discuss exposure considerations in human safety assessment of industrial products and reach consensus on regulatory acceptance of exposure assessment approaches and areas for future research. The forum recognized the widespread use of exposure information across industries and the potential contribution of EPAA in promoting the use of exposure data for human safety assessment.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2023)
Review
Toxicology
Thalia De Castelbajac, Kiara Aiello, Celia Garcia Arenas, Terje Svingen, Louise Ramhoj, Daniel Zalko, Robert Barouki, Tamara Vanhaecke, Vera Rogiers, Marc Audebert, Michael Oelgeschlaeger, Albert Braeuning, Etienne Blanc, Tamara Tal, Joelle Rueegg, Ellen Fritsche, Philip Marx-Stoelting, Gilles Riviere
Summary: New approach methodologies (NAMs) have the potential to significantly impact regulatory risk assessment, but their implementation faces challenges. The PARC project aims to address these challenges and develop innovative methods to improve chemical risk assessment. By focusing on essential regulatory data gaps, PARC intends to provide reliable assessment tools for next-generation risk assessment. Rating: 8 out of 10.
FRONTIERS IN TOXICOLOGY
(2023)
Review
Toxicology
Louise Ramhoj, Marta Axelstad, Yoni Baert, Ana I. Canas-Portilla, Frederic Chalmel, Lars Dahmen, Antonio De La Vieja, Bertrand Evrard, Ann-Cathrin Haigis, Timo Hamers, Kim Heikamp, Henrik Holbech, Patricia Iglesias-Hernandez, Dries Knapen, Lorna Marchandise, Jane E. Morthorst, Nikolai Georgiev Nikolov, Ana C. V. E. Nissen, Michael Oelgeschlaeger, Kostja Renko, Vera Rogiers, Gerrit Schueuermann, Evelyn Stinckens, Mette H. Stub, Monica Torres-Ruiz, Majorie Van Duursen, Tamara Vanhaecke, Lucia Vergauwen, Eva Bay Wedebye, Terje Svingen
Summary: Current test strategies for identifying thyroid hormone (TH) system disruptors are insufficient for robust chemical risk assessment, and alternative test methods are needed to infer a causal relationship between initial chemical disruption and adverse outcomes. This project aims to develop specific new approaches to TH system disruption by characterizing in vivo mechanisms of action and incorporating non-mammalian vertebrate test species alongside traditional laboratory rat species and human-derived in vitro assays.
FRONTIERS IN TOXICOLOGY
(2023)
Review
Medicine, Research & Experimental
Winfried Neuhaus, Birgit Reininger-Gutmann, Beate Rinner, Roberto Plasenzotti, Doris Wilflingseder, Joery De Kock, Tamara Vanhaecke, Vera Rogiers, Dagmar Jirova, Kristina Kejlova, Lisbeth E. Knudsen, Rasmus Normann Nielsen, Burkhard Kleuser, Vivian Kral, Christa Thoene-Reineke, Thomas Hartung, Giorgia Pallocca, Costanza Rovida, Marcel Leist, Stefan Hippenstiel, Annemarie Lang, Ida Retter, Stephanie Kraemer, Peter Jedlicka, Katharina Ameli, Ellen Fritsche, Julia Tigges, Eliska Kuchovska, Manuela Buettner, Andre Bleich, Nadine Baumgart, Jan Baumgart, Marcus W. Meinhardt, Rainer Spanagel, Sabine Chourbaji, Bettina Kraenzlin, Bettina Seeger, Maren von Koeckritz-Blickwede, Jose M. Sanchez-Morgado, Viola Galligioni, Daniel Ruiz-Perez, Dania Movia, Adriele Prina-Mello, Arti Ahluwalia, Valeria Chiono, Arno C. Gutleb, Marthe Schmit, Bea van Golen, Leane van Weereld, Anne Kienhuis, Erica van Oort, Jan van der Valk, Adrian Smith, Joanna Roszak, Maciej Stepnik, Zuzanna Sobanska, Edyta Reszka, I. Anna S. Olsson, Nuno Henrique Franco, Bogdan Sevastre, Helena Kandarova, Sara Capdevila, Jessica Johansson, Emma Svensk, Christopher R. Cederroth, Jenny Sandstroem, Ian Ragan, Nataliia Bubalo, Jens Kurreck, Horst Spielmann
Summary: Three Rs centres and platforms are dedicated to the Replacement, Reduction and Refinement of animal use in experiments. They play a crucial role in promoting the implementation of Directive 2010/63/EU and disseminating information.
ATLA-ALTERNATIVES TO LABORATORY ANIMALS
(2022)
Article
Medicine, Legal
Fiona Sewell, Ian Ragan, Graham Horgan, David Andrew, Thomas Holmes, Irene Manou, Boris P. Mueller, Tim Rowan, Barbara G. Schmitt, Marco Corvaro
Summary: There are currently three test guidelines for acute oral toxicity studies, but the subjectivity of one guideline may be hindering its wider use. In order to address this, the NC3Rs and EPAA collaborated to analyze historical data and provide recommendations on the recognition of 'evident toxicity'.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2024)
Article
Medicine, Legal
Michael DeVito, Bas Bokkers, Majorie B. M. van Duursen, Karin van Ede, Mark Feeley, Elsa Antunes Fernandes Gaspar, Laurie Haws, Sean Kennedy, Richard E. Peterson, Ron Hoogenboom, Keiko Nohara, Kim Petersen, Cynthia Rider, Martin Rose, Stephen Safe, Dieter Schrenk, Matthew W. Wheeler, Daniele S. Wikoff, Bin Zhao, Martin van den Berg
Summary: In October 2022, the World Health Organization reevaluated the toxic equivalency factors (TEFs) for chlorinated dioxin-like compounds in a panel convened in Lisbon. This effort utilized an updated database, Bayesian dose response modeling, and meta-analysis to derive Best-Estimate TEFs. Applying these new TEFs may result in lower total toxic equivalents for dioxin-like chemicals.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2024)