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 Hellfeld,Ruben Strecker,Katharina Brotzmann,Lisa Baumann,Thomas Braunbeck

doi:10.1186/s12302-020-00398-3

Rebecca Von Hellfeld, Ruben Strecker + Show 3 more

Open Access

https://doi.org/10.1186/s12302-020-00398-3

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Abstract

BackgroundThe 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.ResultsWith 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.ConclusionFor 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.

Highlights

The Fish Embryo Acute Toxicity (FET) test with the zebrafish (Danio rerio) embryo, the Organization for economic co-operation and development (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)
Formal toxicity data derived from fish embryo acute toxicity (FET) tests The toxicity of the test compounds was determined after 96 h of exposure as both effect concentrations (EC) and Lethal concentrations (LC) at the 10 and 50% levels (Table 1)
The five test compounds dissolved in 1% dimethyl sulfoxide (DMSO) (MPP+ iodide, PCB 180, rifampicin, sulfisoxazole, and taxol) due to poor solubility did not show any effects

Summary

Introduction

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). With the implementation of the European chemical policy REACH (Registration, Evaluation, Authorization and Restriction of Chemicals [14]) and the European Cosmetics Directive [15], there is a clear mandate to strongly promote the development of alternative methods according to the 3Rs principle for “Replacement, Reduction, and Refinement” [16] and to preferentially use data generated by alternative methods whenever validated methods are available [14] All these considerations are calling for the replacement of acute toxicity and teratogenicity testing traditionally founded on animal models by adverse outcome pathway (AOP)based biomarker studies [17, 18] and in vitro models [19] along with more 3R-compatible in vivo models [13, 20]. ECHA so far refuses to accept the FET test as a stand-alone alternative to OECD TG 203 for regulatory purposes [29], the FET test has found wide acceptance in science and even proved to have a higher sensitivity and better correspondence to humans than other whole organism models [30,31,32]

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