PUBLICATION
Detection and prioritization of developmentally neurotoxic and/or neurotoxic compounds using zebrafish
- Authors
- Quevedo, C., Behl, M., Ryan, K., Paules, R.S., Alday, A., Muriana, A., Alzualde, A.
- ID
- ZDB-PUB-181207-27
- Date
- 2018
- Source
- Toxicological sciences : an official journal of the Society of Toxicology 168(1): 225-240 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Biological Assay
- Embryo, Nonmammalian/drug effects*
- Flame Retardants/toxicity
- Larva/drug effects*
- Motor Activity/drug effects
- Neurotoxicity Syndromes*
- Pesticides/toxicity
- Pharmaceutical Preparations
- Small Molecule Libraries
- Swimming
- Toxicity Tests/methods*
- Zebrafish/growth & development*
- PubMed
- 30521027 Full text @ Toxicol. Sci.
Citation
Quevedo, C., Behl, M., Ryan, K., Paules, R.S., Alday, A., Muriana, A., Alzualde, A. (2018) Detection and prioritization of developmentally neurotoxic and/or neurotoxic compounds using zebrafish. Toxicological sciences : an official journal of the Society of Toxicology. 168(1):225-240.
Abstract
The standard methods for toxicity testing using rodent models cannot keep pace with the increasing number of chemicals in our environment due to time and resource limitations. Hence, there is an unmet need for fast, sensitive and cost-effective alternate models to reliably predict toxicity. As part of Tox21 Phase III's effort, a 90-compound library was created and made available to researchers to screen for neurotoxicants using novel technology and models. The chemical library was evaluated in zebrafish in a dose range finding test for embryo-toxicity (i.e., mortality or morphological alterations induced by each chemical). In addition, embryos exposed to the LEL (lowest effect level) and non-observable effect level were used to measure the internal concentration of the chemicals within the embryos by bioanalysis. Finally, considering the LEL as the highest testing concentration, a functional assay was performed based on locomotor activity alteration in response to light-dark changes. The quality control chemicals included in the library, i.e. negative controls and replicated chemicals, indicate that the assays performed were reliable. The use of analytical chemistry pointed out the importance of measuring chemical concentration inside embryos, and in particular, in the case of negative chemicals to avoid false negative classification. Overall, the proposed approach presented a good sensitivity and supports the inclusion of zebrafish assays as a reliable, relevant and efficient screening tool to identify, prioritize and evaluate chemical toxicity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping