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From cutting edge to guideline: A first step in harmonization of the zebrafish embryotoxicity test (ZET) by describing the most optimal test conditions and morphology scoring system
Institution:1. WIL Research Europe B.V., Hambakenwetering 7, 5231 , DD''s-Hertogenbosch, The Netherlands;2. Toxicology, Radboud University Medical Centre, Nijmegen, The Netherlands;3. Toxicology and Environmental Health, Utrecht University, Utrecht, The Netherlands;1. Laboratório de Ecotoxicologia e Biossegurança, Embrapa CNPMA, Jaguariúna, SP, Brazil;2. Programa de Pós-graduação em Biologia Funcional e Molecular, UNICAMP, Campinas, SP, Brazil;3. Laboratório da Ciência das Plantas Daninhas, Instituto Biológico, APTA/SAA, Campinas, SP, Brazil;4. Departamento de Engenharia Ambiental, UNESP, Sorocaba, SP, Brazil;1. University of Houston, Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, Houston, TX 77204, USA;2. Karolinska Institutet, Department of Biosciences and Nutrition, 14183 Huddinge, Sweden;3. North Carolina State University, Department of Biological Sciences, Bioinformatics Research Center, Raleigh, NC 27695-7614, USA;1. UFZ – Helmholtz Centre for Environmental Research, Department of Cell Toxicology, Permoserstr. 15, 04318, Leipzig, Germany;2. UFZ – Helmholtz Centre for Environmental Research, Department of Bioanalytical Ecotoxicology, Permoserstr. 15, 04318, Leipzig, Germany;3. RWTH Aachen University, Institute for Environmental Research, Biologie V, Worringerweg 1, 52074, Aachen, Germany;4. Eberhard Karls University Tübingen, Center for Applied Geosciences, Environmental Toxicology, Hölderlinstr. 12, 72074, Tübingen, Germany;1. Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium;2. Department of Environmental Engineering, Technical University of Denmark, Miljoevej 113, 2800 Kgs. Lyngby, Denmark;3. Toxicological Centre, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium;4. Systemic Physiological and Ecotoxicological Research (SPHERE), Department of Biology, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerpen, Belgium
Abstract:In the last couple of years, the interest in the zebrafish embryotoxicity test (ZET) for use in developmental toxicity assessment has been growing exponentially. This is also evident from the recent proposal for updating the ICHS5 guideline. The methodology of the ZET used by the different groups varies greatly. To further evaluate its successfulness and to take the ZET to the next level, harmonization of procedures is crucial. In the present study, based on literature and empirical data, the most optimal study design regarding temperature, test chamber, exposure period, presence of chorion, solvent use, exposure method, choice of concentrations, and teratogenic classification is proposed. Furthermore, our morphology scoring system is reported in detail as protocol to further enhance study design harmonization.
Keywords:Zebrafish  Zebrafish embryotoxicity test (ZET)  Teratogenicity  Morphology scoring system  Harmonization  3R's
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