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Assessing Combined Effects for Mixtures of Similar and Dissimilar Acting Neuroactive Substances on Zebrafish Embryo Movement

Risk assessment of chemicals is usually conducted for individual chemicals whereas mixtures of chemicals occur in the environment. Considering that neuroactive chemicals are a group of contaminants that dominate the environment, it is then imperative to understand the combined effects of mixtures. T...

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Autores principales: Ogungbemi, Afolarin O., Massei, Riccardo, Altenburger, Rolf, Scholz, Stefan, Küster, Eberhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148591/
https://www.ncbi.nlm.nih.gov/pubmed/34066629
http://dx.doi.org/10.3390/toxics9050104
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author Ogungbemi, Afolarin O.
Massei, Riccardo
Altenburger, Rolf
Scholz, Stefan
Küster, Eberhard
author_facet Ogungbemi, Afolarin O.
Massei, Riccardo
Altenburger, Rolf
Scholz, Stefan
Küster, Eberhard
author_sort Ogungbemi, Afolarin O.
collection PubMed
description Risk assessment of chemicals is usually conducted for individual chemicals whereas mixtures of chemicals occur in the environment. Considering that neuroactive chemicals are a group of contaminants that dominate the environment, it is then imperative to understand the combined effects of mixtures. The commonly used models to predict mixture effects, namely concentration addition (CA) and independent action (IA), are thought to be suitable for mixtures of similarly or dissimilarly acting components, respectively. For mixture toxicity prediction, one important challenge is to clarify whether to group neuroactive substances based on similar mechanisms of action, e.g., same molecular target or rather similar toxicological response, e.g., hyper- or hypoactivity (effect direction). We addressed this by using the spontaneous tail coiling (STC) of zebrafish embryos, which represents the earliest observable motor activity in the developing neural network, as a model to elucidate the link between the mechanism of action and toxicological response. Our objective was to answer the following two questions: (1) Can the mixture models CA or IA be used to predict combined effects for neuroactive chemical mixtures when the components share a similar mode of action (i.e., hyper- or hypoactivity) but show different mechanism of action? (2) Will a mixture of chemicals where the components show opposing effect directions result in an antagonistic combined effect? Results indicate that mixture toxicity of chemicals such as propafenone and abamectin as well as chlorpyrifos and hexaconazole that are known to show different mechanisms of action but similar effect directions were predictable using CA and IA models. This could be interpreted with the convergence of effects on the neural level leading to either a collective activation or inhibition of synapses. We also found antagonistic effects for mixtures containing substances with opposing effect direction. Finally, we discuss how the STC may be used to amend risk assessment.
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spelling pubmed-81485912021-05-26 Assessing Combined Effects for Mixtures of Similar and Dissimilar Acting Neuroactive Substances on Zebrafish Embryo Movement Ogungbemi, Afolarin O. Massei, Riccardo Altenburger, Rolf Scholz, Stefan Küster, Eberhard Toxics Article Risk assessment of chemicals is usually conducted for individual chemicals whereas mixtures of chemicals occur in the environment. Considering that neuroactive chemicals are a group of contaminants that dominate the environment, it is then imperative to understand the combined effects of mixtures. The commonly used models to predict mixture effects, namely concentration addition (CA) and independent action (IA), are thought to be suitable for mixtures of similarly or dissimilarly acting components, respectively. For mixture toxicity prediction, one important challenge is to clarify whether to group neuroactive substances based on similar mechanisms of action, e.g., same molecular target or rather similar toxicological response, e.g., hyper- or hypoactivity (effect direction). We addressed this by using the spontaneous tail coiling (STC) of zebrafish embryos, which represents the earliest observable motor activity in the developing neural network, as a model to elucidate the link between the mechanism of action and toxicological response. Our objective was to answer the following two questions: (1) Can the mixture models CA or IA be used to predict combined effects for neuroactive chemical mixtures when the components share a similar mode of action (i.e., hyper- or hypoactivity) but show different mechanism of action? (2) Will a mixture of chemicals where the components show opposing effect directions result in an antagonistic combined effect? Results indicate that mixture toxicity of chemicals such as propafenone and abamectin as well as chlorpyrifos and hexaconazole that are known to show different mechanisms of action but similar effect directions were predictable using CA and IA models. This could be interpreted with the convergence of effects on the neural level leading to either a collective activation or inhibition of synapses. We also found antagonistic effects for mixtures containing substances with opposing effect direction. Finally, we discuss how the STC may be used to amend risk assessment. MDPI 2021-05-06 /pmc/articles/PMC8148591/ /pubmed/34066629 http://dx.doi.org/10.3390/toxics9050104 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ogungbemi, Afolarin O.
Massei, Riccardo
Altenburger, Rolf
Scholz, Stefan
Küster, Eberhard
Assessing Combined Effects for Mixtures of Similar and Dissimilar Acting Neuroactive Substances on Zebrafish Embryo Movement
title Assessing Combined Effects for Mixtures of Similar and Dissimilar Acting Neuroactive Substances on Zebrafish Embryo Movement
title_full Assessing Combined Effects for Mixtures of Similar and Dissimilar Acting Neuroactive Substances on Zebrafish Embryo Movement
title_fullStr Assessing Combined Effects for Mixtures of Similar and Dissimilar Acting Neuroactive Substances on Zebrafish Embryo Movement
title_full_unstemmed Assessing Combined Effects for Mixtures of Similar and Dissimilar Acting Neuroactive Substances on Zebrafish Embryo Movement
title_short Assessing Combined Effects for Mixtures of Similar and Dissimilar Acting Neuroactive Substances on Zebrafish Embryo Movement
title_sort assessing combined effects for mixtures of similar and dissimilar acting neuroactive substances on zebrafish embryo movement
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148591/
https://www.ncbi.nlm.nih.gov/pubmed/34066629
http://dx.doi.org/10.3390/toxics9050104
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