- Email: [email protected]
Zebrafish embryotoxicity test for developmental (neuro)toxicity: Demo case of an integrated screening approach system using anti-epileptic drugs
Reproductive Toxicology 1 (2015) 3
Contents lists available at ScienceDirect
Reproductive Toxicology journal homepage: www.elsevier.com/locate/reprotox
Elsevier Award Lecture: Best manuscript in Reproductive Toxicology in 2014
Sponsored by Elsevier The best manuscript in Reproductive Toxicology in 2014 was voted by the ETS Committee from a short list provided by the Editorin-Chief of the Reproductive Toxicology journal. In recognition of this achievement, the ETS invites one of the authors to present the winning paper at the ETS annual meeting the following year. Elsevier contributes to the speaker’s expenses to attend the meeting. Reproductive Toxicology is the official journal of the ETS. Congratulations to the authors of the best manuscript published in Reproductive Toxicology in 2014. A-2 Zebrafish embryotoxicity test for developmental (neuro)toxicity: Demo case of an integrated screening approach system using anti-epileptic drugs Anna Beker van Woudenberg 1 , Cor Snel 2 , Eke Rijkmans 1 , Didima de Groot 1 , Marga Bouma 1 , Sanne Hermsen 3 , Aldert Piersma 3 , Aswin Menke 2 , André Wolterbeek 1 1 TNO, Research Group Risk Analysis for Products In Development (RAPID), Zeist, The Netherlands
0890-6238/$ – see front matter
2
TNO Triskelion B.V., Zeist, The Netherlands Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands 3
To improve the predictability of the zebrafish embryotoxicity test (ZET) for developmental (neuro)toxicity screening, we used a multiple-endpoints strategy, including morphology, motor activity (MA), histopathology and kinetics. The model compounds used were antiepileptic drugs (AEDs): valproic acid (VPA), carbamazepine (CBZ), ethosuximide (ETH) and levetiracetam (LEV). For VPA, histopathology was the most sensitive parameter, showing effects already at 60 M. For CBZ, morphology and MA were the most sensitive parameters, showing effects at 180 M. For ETH, all endpoints showed similar sensitivity (6.6 mM), whereas MA was the most sensitive parameter for LEV (40 mM). Inclusion of kinetics did not alter the absolute ranking of the compounds, but the relative potency was changed considerably. Taking all together, this demo-case study showed that inclusion of multiple-endpoints in ZET may increase the sensitivity of the assay, contribute to the elucidation of the mode of toxic action and to a better definition of the applicability domain of ZET. http://dx.doi.org/10.1016/j.reprotox.2015.07.007
Contents lists available at ScienceDirect
Reproductive Toxicology journal homepage: www.elsevier.com/locate/reprotox
Elsevier Award Lecture: Best manuscript in Reproductive Toxicology in 2014
Sponsored by Elsevier The best manuscript in Reproductive Toxicology in 2014 was voted by the ETS Committee from a short list provided by the Editorin-Chief of the Reproductive Toxicology journal. In recognition of this achievement, the ETS invites one of the authors to present the winning paper at the ETS annual meeting the following year. Elsevier contributes to the speaker’s expenses to attend the meeting. Reproductive Toxicology is the official journal of the ETS. Congratulations to the authors of the best manuscript published in Reproductive Toxicology in 2014. A-2 Zebrafish embryotoxicity test for developmental (neuro)toxicity: Demo case of an integrated screening approach system using anti-epileptic drugs Anna Beker van Woudenberg 1 , Cor Snel 2 , Eke Rijkmans 1 , Didima de Groot 1 , Marga Bouma 1 , Sanne Hermsen 3 , Aldert Piersma 3 , Aswin Menke 2 , André Wolterbeek 1 1 TNO, Research Group Risk Analysis for Products In Development (RAPID), Zeist, The Netherlands
0890-6238/$ – see front matter
2
TNO Triskelion B.V., Zeist, The Netherlands Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands 3
To improve the predictability of the zebrafish embryotoxicity test (ZET) for developmental (neuro)toxicity screening, we used a multiple-endpoints strategy, including morphology, motor activity (MA), histopathology and kinetics. The model compounds used were antiepileptic drugs (AEDs): valproic acid (VPA), carbamazepine (CBZ), ethosuximide (ETH) and levetiracetam (LEV). For VPA, histopathology was the most sensitive parameter, showing effects already at 60 M. For CBZ, morphology and MA were the most sensitive parameters, showing effects at 180 M. For ETH, all endpoints showed similar sensitivity (6.6 mM), whereas MA was the most sensitive parameter for LEV (40 mM). Inclusion of kinetics did not alter the absolute ranking of the compounds, but the relative potency was changed considerably. Taking all together, this demo-case study showed that inclusion of multiple-endpoints in ZET may increase the sensitivity of the assay, contribute to the elucidation of the mode of toxic action and to a better definition of the applicability domain of ZET. http://dx.doi.org/10.1016/j.reprotox.2015.07.007