Cargando…

Concurrent Evaluation of Mortality and Behavioral Responses: A Fast and Efficient Testing Approach for High-Throughput Chemical Hazard Identification

The continual introduction of new chemicals into the market necessitates fast, efficient testing strategies for evaluating their toxicity. Ideally, these high-throughput screening (HTS) methods should capture the entirety of biological complexity while minimizing reliance on expensive resources that...

Descripción completa

Detalles Bibliográficos
Autores principales: Thunga, Preethi, Truong, Lisa, Tanguay, Robyn L., Reif, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8915815/
https://www.ncbi.nlm.nih.gov/pubmed/35295121
http://dx.doi.org/10.3389/ftox.2021.670496
_version_ 1784668134957907968
author Thunga, Preethi
Truong, Lisa
Tanguay, Robyn L.
Reif, David M.
author_facet Thunga, Preethi
Truong, Lisa
Tanguay, Robyn L.
Reif, David M.
author_sort Thunga, Preethi
collection PubMed
description The continual introduction of new chemicals into the market necessitates fast, efficient testing strategies for evaluating their toxicity. Ideally, these high-throughput screening (HTS) methods should capture the entirety of biological complexity while minimizing reliance on expensive resources that are required to assess diverse phenotypic endpoints. In recent years, the zebrafish (Danio rerio) has become a preferred vertebrate model to conduct rapid in vivo toxicity tests. Previously, using HTS data on 1060 chemicals tested as part of the ToxCast program, we showed that early, 24 h post-fertilization (hpf), behavioral responses of zebrafish embryos are predictive of later, 120 h post-fertilization, adverse developmental endpoints—indicating that embryonic behavior is a useful endpoint related to observable morphological effects. Here, our goal was to assess the contributions (i.e., information gain) from multiple phenotypic data streams and propose a framework for efficient identification of chemical hazards. We systematically swept through analysis parameters for data on 24 hpf behavior, 120 hpf behavior, and 120 hpf morphology to optimize settings for each of these assays. We evaluated the concordance of data from behavioral assays with that from morphology. We found that combining information from behavioral and mortality assessments captures early signals of potential chemical hazards, obviating the need to evaluate a comprehensive suite of morphological endpoints in initial screens for toxicity. We have demonstrated that such a screening strategy is useful for detecting compounds that elicit adverse morphological responses, in addition to identifying hazardous compounds that do not disrupt the underlying morphology. The application of this design for rapid preliminary toxicity screening will accelerate chemical testing and aid in prioritizing chemicals for risk assessment.
format Online
Article
Text
id pubmed-8915815
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-89158152022-03-15 Concurrent Evaluation of Mortality and Behavioral Responses: A Fast and Efficient Testing Approach for High-Throughput Chemical Hazard Identification Thunga, Preethi Truong, Lisa Tanguay, Robyn L. Reif, David M. Front Toxicol Toxicology The continual introduction of new chemicals into the market necessitates fast, efficient testing strategies for evaluating their toxicity. Ideally, these high-throughput screening (HTS) methods should capture the entirety of biological complexity while minimizing reliance on expensive resources that are required to assess diverse phenotypic endpoints. In recent years, the zebrafish (Danio rerio) has become a preferred vertebrate model to conduct rapid in vivo toxicity tests. Previously, using HTS data on 1060 chemicals tested as part of the ToxCast program, we showed that early, 24 h post-fertilization (hpf), behavioral responses of zebrafish embryos are predictive of later, 120 h post-fertilization, adverse developmental endpoints—indicating that embryonic behavior is a useful endpoint related to observable morphological effects. Here, our goal was to assess the contributions (i.e., information gain) from multiple phenotypic data streams and propose a framework for efficient identification of chemical hazards. We systematically swept through analysis parameters for data on 24 hpf behavior, 120 hpf behavior, and 120 hpf morphology to optimize settings for each of these assays. We evaluated the concordance of data from behavioral assays with that from morphology. We found that combining information from behavioral and mortality assessments captures early signals of potential chemical hazards, obviating the need to evaluate a comprehensive suite of morphological endpoints in initial screens for toxicity. We have demonstrated that such a screening strategy is useful for detecting compounds that elicit adverse morphological responses, in addition to identifying hazardous compounds that do not disrupt the underlying morphology. The application of this design for rapid preliminary toxicity screening will accelerate chemical testing and aid in prioritizing chemicals for risk assessment. Frontiers Media S.A. 2021-06-15 /pmc/articles/PMC8915815/ /pubmed/35295121 http://dx.doi.org/10.3389/ftox.2021.670496 Text en Copyright © 2021 Thunga, Truong, Tanguay and Reif. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Toxicology
Thunga, Preethi
Truong, Lisa
Tanguay, Robyn L.
Reif, David M.
Concurrent Evaluation of Mortality and Behavioral Responses: A Fast and Efficient Testing Approach for High-Throughput Chemical Hazard Identification
title Concurrent Evaluation of Mortality and Behavioral Responses: A Fast and Efficient Testing Approach for High-Throughput Chemical Hazard Identification
title_full Concurrent Evaluation of Mortality and Behavioral Responses: A Fast and Efficient Testing Approach for High-Throughput Chemical Hazard Identification
title_fullStr Concurrent Evaluation of Mortality and Behavioral Responses: A Fast and Efficient Testing Approach for High-Throughput Chemical Hazard Identification
title_full_unstemmed Concurrent Evaluation of Mortality and Behavioral Responses: A Fast and Efficient Testing Approach for High-Throughput Chemical Hazard Identification
title_short Concurrent Evaluation of Mortality and Behavioral Responses: A Fast and Efficient Testing Approach for High-Throughput Chemical Hazard Identification
title_sort concurrent evaluation of mortality and behavioral responses: a fast and efficient testing approach for high-throughput chemical hazard identification
topic Toxicology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8915815/
https://www.ncbi.nlm.nih.gov/pubmed/35295121
http://dx.doi.org/10.3389/ftox.2021.670496
work_keys_str_mv AT thungapreethi concurrentevaluationofmortalityandbehavioralresponsesafastandefficienttestingapproachforhighthroughputchemicalhazardidentification
AT truonglisa concurrentevaluationofmortalityandbehavioralresponsesafastandefficienttestingapproachforhighthroughputchemicalhazardidentification
AT tanguayrobynl concurrentevaluationofmortalityandbehavioralresponsesafastandefficienttestingapproachforhighthroughputchemicalhazardidentification
AT reifdavidm concurrentevaluationofmortalityandbehavioralresponsesafastandefficienttestingapproachforhighthroughputchemicalhazardidentification