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4143789 
Journal Article 
The fish embryo test (FET): origin, applications, and future 
Braunbeck, T; Kais, B; Lammer, E; Otte, J; Schneider, K; Stengel, D; Strecker, R 
2015 
Yes 
Environmental Science and Pollution Research
ISSN: 0944-1344
EISSN: 1614-7499 
22 
21 
16247-16261 
English 
Originally designed as an alternative for the acute fish toxicity test according to, e.g., OECD TG 203, the fish embryo test (FET) with the zebrafish (Danio rerio) has been optimized, standardized, and validated during an OECD validation study and adopted as OECD TG 236 as a test to assess toxicity of embryonic forms of fish. Given its excellent correlation with the acute fish toxicity test and the fact that non-feeding developmental stages of fish are not categorized as protected stages according to the new European Directive 2010/63/EU on the protection of animals used for scientific purposes, the FET is ready for use not only for range-finding but also as a true alternative for the acute fish toxicity test, as required for a multitude of national and international regulations. If-for ethical reasons-not accepted as a full alternative, the FET represents at least a refinement in the sense of the 3Rs principle. Objections to the use of the FET have mainly been based on the putative lack of biotransformation capacity and the assumption that highly lipophilic and/or high molecular weight substances might not have access to the embryo due to the protective role of the chorion. With respect to bioactivation, the only substance identified so far as not being activated in the zebrafish embryo is allyl alcohol; all other biotransformation processes that have been studied in more detail so far were found to be present, albeit, in some cases, at lower levels than in adult fish. With respect to larger molecules, the extension of the test duration to 96 h (i.e., beyond hatch) has-at least for the substances tested so far-compensated for the reduced access to the embryo; however, more research is necessary to fully explore the applicability of the FET to substances with a molecular weight >3 kDa as well as substances with a neurotoxic mode of action. An extension of the endpoints to also cover sublethal endpoints makes the FET a powerful tool for the detection of teratogenicity, dioxin-like activity, genotoxicity and mutagenicity, neurotoxicity, as well as various forms of endocrine disruption. 
Environmental Studies--Pollution; Fish embryo test; Validation; Alternative test method; OECD guideline; Acute toxicity; Teratogenicity; Genotoxicity; Endocrine disruption; Neurotoxicity; Biotransformation; Cytochrome P450; Studies; Environmental science; Zebrafish; Embryos; Toxicity; Endocrine system; Risk assessment; 9130:Experimental/theoretical; 1540:Pollution control