(http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited Zebrafish toxicogenomic responses

Microarray profiling of zebrafish embryos exposed to a range of environmental toxicants revealed distinct expression profiles for each of the toxicants tested.

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The numbers of potential neurotoxicants in the environment are raising and pose a great risk for humans and the environment. Currently neurotoxicity assessment is mostly performed to predict and prevent harm to human populations. Despite all the efforts invested in the last years in developing novel in vitro or in silico test systems, in vivo tests with rodents are still the only accepted test for neurotoxicity risk assessment in Europe. Despite an increasing number of reports of species showing altered behaviour, neurotoxicity assessment for species in the environment is not required and therefore mostly not performed. Considering the increasing numbers of environmental contaminants with potential neurotoxic potential, eco-neurotoxicity should be also considered in risk assessment. In order to do so novel test systems are needed that can cope with species differences within ecosystems. In the field, online-biomonitoring systems using behavioural information could be used to detect neurotoxic effects and effect-directed analyses could be applied to identify the neurotoxicants causing the effect. Additionally, toxic pressure calculations in combination with mixture modelling could use environmental chemical monitoring data to predict adverse effects and prioritize pollutants for laboratory testing. Cheminformatics based on computational toxicological data from in vitro and in vivo studies could help to identify potential neurotoxicants. An array of in vitro assays covering different modes of action could be applied to screen compounds for neurotoxicity. The selection of in vitro assays could be guided by AOPs relevant for eco-neurotoxicity. In order to be able to perform risk assessment for eco-neurotoxicity, methods need to focus on the most sensitive species in an ecosystem. A test battery using species from different trophic levels might be the best approach. To implement eco-neurotoxicity assessment into European risk assessment, cheminformatics and in vitro screening tests could be used as first approach to identify eco-neurotoxic pollutants. In a second step, a small species test battery could be applied to assess the risks of ecosystems.

Testing of compounds for neurotoxicity has become increasingly important in recent years. It has been shown that neurological disorders like autism may be related to chemical exposures, which may play a crucial role in the progression of these diseases. Special attention has been be given to the substances causing developmental neurotoxicity as the developing nervous system is more vulnerable to impacts by chemicals than the adult nervous system. The zebrafish (Danio rerio) is a well-established model species in developmental biology and an emerging model in behavioural and neurological studies. Zebrafish larvae display numerous behavioural patterns highly similar to rodents and humans. Their physical characteristics make them well suited for automated high-throughput screening. In the last years, the number of behavioural studies conducted with zebrafish larvae has increased notably. The goal of this review is to provide an overview of behavioural assays commonly used to test substances for developmental neurotoxicity. Literature from 1995 to 2014 was reviewed and focussed on assays performed with zebrafish larvae younger than 7 days post fertilization (dpf). The behavioural tests were scrutinized, and parameters describing the different experimental setups were defined. In the next step, we investigated if differences in the experimental parameters alter the outcome of the test. In order to test the comparability of behavioural assays, we analysed several studies using ethanol, valproate and pentylenetetrazole as model substances. Based on our findings, we provide recommendations which could help improve future behavioural studies performed with zebrafish larvae.