PUBLICATION
The fish embryo toxicity test (FET) - identification of compounds with weak toxicity and analysis of behavioral effects to improve prediction of acute toxicity for neurotoxic compounds
- Authors
- Klüver, N., König, M., Ortmann, J., Massei, R., Paschke, A., Kuehne, R., Scholz, S.
- ID
- ZDB-PUB-150506-8
- Date
- 2015
- Source
- Environmental science & technology 49(11): 7002-11 (Journal)
- Registered Authors
- Klüver, Nils
- Keywords
- none
- MeSH Terms
-
- Animals
- Behavior, Animal/drug effects*
- Biological Assay
- Environmental Exposure/analysis
- Lethal Dose 50
- Motor Activity/drug effects
- Neurotoxins/toxicity*
- Regression Analysis
- Time Factors
- Toxicity Tests, Acute*
- Zebrafish/embryology*
- PubMed
- 25939044 Full text @ Env. Sci. Tech.
Citation
Klüver, N., König, M., Ortmann, J., Massei, R., Paschke, A., Kuehne, R., Scholz, S. (2015) The fish embryo toxicity test (FET) - identification of compounds with weak toxicity and analysis of behavioral effects to improve prediction of acute toxicity for neurotoxic compounds. Environmental science & technology. 49(11):7002-11.
Abstract
The fish embryo toxicity test has been proposed as an alternative for the acute fish toxicity test, but concerns have been raised for its predictivity given that a few compounds have been shown to exhibit a weak acute toxicity in the fish embryo. In order to better define the applicability domain and improve the predictive capacity of the fish embryo test, we performed a systematic analysis of existing fish embryo and acute fish toxicity data. A correlation analysis of a total of 153 compounds identified 28 compound with a weaker or no toxicity in the fish embryo test. Eleven of these compounds exhibited a neurotoxic mode of action. We selected a subset of eight compounds with weaker or no embryo toxicity (cyanazine, picloram, aldicarb, azinphos-methyl, dieldrin, diquat dibromide, endosulfan and esfenvalerate) to study toxicokinetics and a neurotoxic mode of action as potential reasons for the deviating fish embryo toxicity. Published fish embryo LC50 values were confirmed by experimental analysis of zebrafish embryo LC50 according to OECD guideline 236. Except for diquat dibromide, internal concentration analysis did not indicate a potential relation of the low sensitivity of fish embryos to a limited uptake of the compounds. Analysis of locomotor activity of diquat dibromide and the neurotoxic compounds in 98 hpf embryos (exposed for 96h) indicated a specific effect on behavior (embryonic movement) for the neurotoxic compounds. The EC50s of behavior for neurotoxic compounds were close to the acute fish toxicity LC50. Our data provided first evidence that the applicability domain of the fish embryo test (LC50s determination) may exclude neurotoxic compounds. However, neurotoxic compounds could be identified by changes in embryonic locomotion. Although a quantitative prediction of acute fish toxicity LC50 using behavioral assays in fish embryos may yet not be possible, the identification of neurotoxicity could trigger the conduction of a conventional fish acute toxicity tests or application of assessment factors while considering the very good fish embryo - acute fish toxicity correlation for other compounds.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping