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      Adverse effects in the fish embryo acute toxicity (FET) test: a catalogue of unspecific morphological changes versus more specific effects in zebrafish (Danio rerio) embryos

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          Abstract

          Background

          The Fish Embryo Acute Toxicity (FET) test with the zebrafish ( Danio rerio) embryo, the OECD test guideline (TG) 236, has been designed as an alternative for acute fish toxicity testing such as the OECD Acute Fish Toxicity Test (TG 203). To provide equivalent sensitivity to the acute fish test, the original FET test was designed to use only four morphological core endpoints: coagulation of the embryo, lack of somite formation, lack of heart beat, and non-detachment of the tail. These endpoints were selected due to (1) their association with mortality, directly or indirectly, (2) improve the practicality for screening by well-trained technical staff, and (3) the endpoints being relatively simple morphological alterations.

          Results

          With the growing need to understand the developmental toxicity of compounds found in the environment, the FET protocol has repeatedly been extended to a multitude of additional morphological endpoints that also allow the monitoring of teratogenicity. As the extensive use of the FET test has generated a multitude of observations in the scientific literature, a harmonisation of the terminology used for the description of the morphological effects seen after chemical exposure has become necessary.

          Conclusion

          For this end, the present communication provides an overview of both common and selected more specific morphological effects seen in zebrafish embryos after exposure to a wide variety of chemical substances together with suggestions for a harmonised nomenclature.

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          Most cited references96

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          Adverse outcome pathway (AOP) development I: strategies and principles.

          An adverse outcome pathway (AOP) is a conceptual framework that organizes existing knowledge concerning biologically plausible, and empirically supported, links between molecular-level perturbation of a biological system and an adverse outcome at a level of biological organization of regulatory relevance. Systematic organization of information into AOP frameworks has potential to improve regulatory decision-making through greater integration and more meaningful use of mechanistic data. However, for the scientific community to collectively develop a useful AOP knowledgebase that encompasses toxicological contexts of concern to human health and ecological risk assessment, it is critical that AOPs be developed in accordance with a consistent set of core principles. Based on the experiences and scientific discourse among a group of AOP practitioners, we propose a set of five fundamental principles that guide AOP development: (1) AOPs are not chemical specific; (2) AOPs are modular and composed of reusable components-notably key events (KEs) and key event relationships (KERs); (3) an individual AOP, composed of a single sequence of KEs and KERs, is a pragmatic unit of AOP development and evaluation; (4) networks composed of multiple AOPs that share common KEs and KERs are likely to be the functional unit of prediction for most real-world scenarios; and (5) AOPs are living documents that will evolve over time as new knowledge is generated. The goal of the present article was to introduce some strategies for AOP development and detail the rationale behind these 5 key principles. Consideration of these principles addresses many of the current uncertainties regarding the AOP framework and its application and is intended to foster greater consistency in AOP development.
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            Confocal Imaging–Guided Laser Ablation of Basal Cell Carcinomas: An Ex Vivo Study

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              Zebrafish embryos as an alternative to animal experiments--a commentary on the definition of the onset of protected life stages in animal welfare regulations.

              Worldwide, the zebrafish has become a popular model for biomedical research and (eco)toxicology. Particularly the use of embryos is receiving increasing attention, since they are considered as replacement method for animal experiments. Zebrafish embryos allow the analysis of multiple endpoints ranging from acute and developmental toxicity determination to complex functional genetic and physiological analysis. Particularly the more complex endpoints require the use of post-hatched eleutheroembryo stages. According to the new EU Directive 2010/63/EU on the protection of animals used for scientific purposes, the earliest life-stages of animals are not defined as protected and, therefore, do not fall into the regulatory frameworks dealing with animal experimentation. Independent feeding is considered as the stage from which free-living larvae are subject to regulations for animal experimentation. However, despite this seemingly clear definition, large variations exist in the interpretation of this criterion by national and regional authorities. Since some assays require the use of post-hatched stages up to 120 h post fertilization, the literature and available data are reviewed in order to evaluate if this stage could still be considered as non-protected according to the regulatory criterion of independent feeding. Based on our analysis and by including criteria such as yolk consumption, feeding and swimming behavior, we conclude that zebrafish larvae can indeed be regarded as independently feeding from 120 h after fertilization. Experiments with zebrafish should thus be subject to regulations for animal experiments from 120 h after fertilization onwards. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Environmental Sciences Europe
                Environ Sci Eur
                Springer Science and Business Media LLC
                2190-4707
                2190-4715
                December 2020
                September 29 2020
                December 2020
                : 32
                : 1
                Article
                10.1186/s12302-020-00398-3
                24926986-f912-4012-9167-930048339d3b
                © 2020

                https://creativecommons.org/licenses/by/4.0

                https://creativecommons.org/licenses/by/4.0

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