Adverse effects in the fish embryo acute toxicity (FET) test: a catalogue of unspecific morphological changes versus mor

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RESEARCH

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 Rebecca von Hellfeld1, Katharina Brotzmann1, Lisa Baumann1, Ruben Strecker1,2 and Thomas Braunbeck1* 

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 nondetachment 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. Keywords:  Zebrafish, OECD TG 236, Embryo toxicity, FET test, Teratogenicity, Spinal defects, Lordosis, Kyphosis, Scoliosis, Craniofacial deformation, Yolk malabsorption Background Increasing amounts of anthropogenic compounds entering the environment have led to the need for reliable and accurate acute toxicity tests [1]. Most regulatoryaccepted models for environmental hazard identification and risk assessment of chemicals, pharmaceuticals, *Correspondence: braunbeck@uni‑hd.de 1 Aquatic Ecology and Toxicology, Centre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 504, 69120 Heidelberg, Germany Full list of author information is available at the end of the article

biocides, additives, and effluents are based on testing with vertebrate models such as rodents and fish [2]. According to the European Chemicals Agency [3], the Acute Fish Toxicity (AFT) test (OECD Test Guideline 203; [4]) is used for the prospective assessment of individual chemicals for environmental classification according to the Globally Harmonised System of Classification, Labelling and Packaging of Chemicals (GHS), a Predicted NoEffect-Concentration (PNEC), and one potential element of the toxicity criterion for the assessm