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other·endocrinology, preclinical research, biomedical research, research methods·PMC10349382

Development of new approach methods for the identification and characterization of endocrine metabolic disruptors—a PARC project

Frontiers in Toxicology · 19 authors, 10 centres

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TL;DR

It is a methods-development project within the EU PARC initiative, with no completed experimental data reported.

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This paper presents planned new approach methods (NAMs) for identifying endocrine metabolism-disrupting chemicals (MDCs) within the EU PARC initiative. Implications are restricted to the conceptual framework for detecting MDCs acting via nuclear receptor pathways related to obesity and metabolic disorders.

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other

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endocrinology

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ORIGINAL PAPER

PMC10349382

Development of new approach methods for the identification and characterization of endocrine metabolic disruptors—a PARC project

Frontiers in Toxicology

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ABSTRACT

Abstract In past times, the analysis of endocrine disrupting properties of chemicals has mainly been focused on (anti-)estrogenic or (anti-)androgenic properties, as well as on aspects of steroidogenesis and the modulation of thyroid signaling. More recently, disruption of energy metabolism and related signaling pathways by exogenous substances, so-called metabolism-disrupting chemicals (MDCs) have come into focus. While general effects such as body and organ weight changes are routinely monitored in animal studies, there is a clear lack of mechanistic test systems to determine and characterize the metabolism-disrupting potential of chemicals. In order to contribute to filling this gap, one of the project within EU-funded Partnership for the Assessment of Risks of Chemicals (PARC) aims at developing novel in vitro methods for the detection of endocrine metabolic disruptors. Efforts will comprise projects related to specific signaling pathways, for example, involving mTOR or xenobiotic-sensing nuclear receptors, studies on hepatocytes, adipocytes and pancreatic beta cells covering metabolic and morphological endpoints, as well as metabolism-related zebrafish-based tests as an alternative to classic rodent bioassays. This paper provides an overview of the approaches and methods of these PARC projects and how this will contribute to the improvement of the toxicological toolbox to identify substances with endocrine disrupting properties and to decipher their mechanisms of action. Keywords: endocrine metabolic disruption, energy metabolism, obesogens, nuclear receptors, adipocytes, liver

CITATION EXPORT

Albert Braeuning, Patrick Balaguer, William Bourguet et al.. Development of new approach methods for the identification and characterization of endocrine metabolic disruptors—a PARC project. Frontiers in Toxicology. (2023). https://doi.org/10.3389/ftox.2023.1212509

AUTHORS

19 · 10 CENTRES

Albert Braeuning, Patrick Balaguer, William Bourguet, Jordi Carreras-Puigvert, Katreece Feiertag, Jorke H Kamstra, Dries Knapen, Dajana Lichtenstein, Philip Marx-Stoelting, Jonne Rietdijk, Kristin Schubert, Ola Spjuth, Evelyn Stinckens, Kathrin Thedieck, Rik van den Boom, Lucia Vergauwen, Martin von Bergen, Neele Wewer, Daniel Zalko

1 Department of Food Safety, German Federal Institute for Risk Assessment, Berlin, Germany
2 IRCM (Institut de Recherche en Cancérologie de Montpellier), Inserm U1194, Université de Montpellier, ICM, Montpellier, France
3 CBS Centre de Biologie Structurale, Université de Montpellier, CNRS, Inserm, Montpellier, France
4 Department of Pharmaceutical Biosciences and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
5 Department of Pesticides Safety, German Federal Institute for Risk Assessment, Berlin, Germany
6 Department of Population Health Sciences, Institute for Risk Assessment Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands
7 Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk, Belgium
8 Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany
9 Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria
10 Toxalim (Research Centre in Food Toxicology), Université de Toulouse, Institut National de Recherche Pour L’Agriculture, L’Alimentation et L’Environnement (INARE), Ecole Nationale Vétérinaire de Toulouse (ENVT), INP-Purpan, Université Paul Sabatier (UPS), Toulouse, France