Cargando…
Mode of Action Classifications in the EnviroTox Database: Development and Implementation of a Consensus MOA Classification
Multiple mode of action (MOA) frameworks have been developed in aquatic ecotoxicology, mainly based on fish toxicity. These frameworks provide information on a key determinant of chemical toxicity, but the MOA categories and level of specificity remain unique to each of the classification schemes. T...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851772/ https://www.ncbi.nlm.nih.gov/pubmed/31269286 http://dx.doi.org/10.1002/etc.4531 |
_version_ | 1783469683100352512 |
---|---|
author | Kienzler, Aude Connors, Kristin A. Bonnell, Mark Barron, Mace G. Beasley, Amy Inglis, Cristina G. Norberg‐King, Teresa J. Martin, Todd Sanderson, Hans Vallotton, Nathalie Wilson, Peter Embry, Michelle R. |
author_facet | Kienzler, Aude Connors, Kristin A. Bonnell, Mark Barron, Mace G. Beasley, Amy Inglis, Cristina G. Norberg‐King, Teresa J. Martin, Todd Sanderson, Hans Vallotton, Nathalie Wilson, Peter Embry, Michelle R. |
author_sort | Kienzler, Aude |
collection | PubMed |
description | Multiple mode of action (MOA) frameworks have been developed in aquatic ecotoxicology, mainly based on fish toxicity. These frameworks provide information on a key determinant of chemical toxicity, but the MOA categories and level of specificity remain unique to each of the classification schemes. The present study aimed to develop a consensus MOA assignment within EnviroTox, a curated in vivo aquatic toxicity database, based on the following MOA classification schemes: Verhaar (modified) framework, Assessment Tool for Evaluating Risk, Toxicity Estimation Software Tool, and OASIS. The MOA classifications from each scheme were first collapsed into one of 3 categories: non–specifically acting (i.e., narcosis), specifically acting, or nonclassifiable. Consensus rules were developed based on the degree of concordance among the 4 individual MOA classifications to attribute a consensus MOA to each chemical. A confidence rank was also assigned to the consensus MOA classification based on the degree of consensus. Overall, 40% of the chemicals were classified as narcotics, 17% as specifically acting, and 43% as unclassified. Sixty percent of chemicals had a medium to high consensus MOA assignment. When compared to empirical acute toxicity data, the general trend of specifically acting chemicals being more toxic is clearly observed for both fish and invertebrates but not for algae. EnviroTox is the first approach to establishing a high‐level consensus across 4 computationally and structurally distinct MOA classification schemes. This consensus MOA classification provides both a transparent understanding of the variation between MOA classification schemes and an added certainty of the MOA assignment. In terms of regulatory relevance, a reliable understanding of MOA can provide information that can be useful for the prioritization (ranking) and risk assessment of chemicals. Environ Toxicol Chem 2019;38:2294–2304. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. |
format | Online Article Text |
id | pubmed-6851772 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68517722019-11-18 Mode of Action Classifications in the EnviroTox Database: Development and Implementation of a Consensus MOA Classification Kienzler, Aude Connors, Kristin A. Bonnell, Mark Barron, Mace G. Beasley, Amy Inglis, Cristina G. Norberg‐King, Teresa J. Martin, Todd Sanderson, Hans Vallotton, Nathalie Wilson, Peter Embry, Michelle R. Environ Toxicol Chem Hazard/Risk Assessment Multiple mode of action (MOA) frameworks have been developed in aquatic ecotoxicology, mainly based on fish toxicity. These frameworks provide information on a key determinant of chemical toxicity, but the MOA categories and level of specificity remain unique to each of the classification schemes. The present study aimed to develop a consensus MOA assignment within EnviroTox, a curated in vivo aquatic toxicity database, based on the following MOA classification schemes: Verhaar (modified) framework, Assessment Tool for Evaluating Risk, Toxicity Estimation Software Tool, and OASIS. The MOA classifications from each scheme were first collapsed into one of 3 categories: non–specifically acting (i.e., narcosis), specifically acting, or nonclassifiable. Consensus rules were developed based on the degree of concordance among the 4 individual MOA classifications to attribute a consensus MOA to each chemical. A confidence rank was also assigned to the consensus MOA classification based on the degree of consensus. Overall, 40% of the chemicals were classified as narcotics, 17% as specifically acting, and 43% as unclassified. Sixty percent of chemicals had a medium to high consensus MOA assignment. When compared to empirical acute toxicity data, the general trend of specifically acting chemicals being more toxic is clearly observed for both fish and invertebrates but not for algae. EnviroTox is the first approach to establishing a high‐level consensus across 4 computationally and structurally distinct MOA classification schemes. This consensus MOA classification provides both a transparent understanding of the variation between MOA classification schemes and an added certainty of the MOA assignment. In terms of regulatory relevance, a reliable understanding of MOA can provide information that can be useful for the prioritization (ranking) and risk assessment of chemicals. Environ Toxicol Chem 2019;38:2294–2304. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. John Wiley and Sons Inc. 2019-09-05 2019-10 /pmc/articles/PMC6851772/ /pubmed/31269286 http://dx.doi.org/10.1002/etc.4531 Text en © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Hazard/Risk Assessment Kienzler, Aude Connors, Kristin A. Bonnell, Mark Barron, Mace G. Beasley, Amy Inglis, Cristina G. Norberg‐King, Teresa J. Martin, Todd Sanderson, Hans Vallotton, Nathalie Wilson, Peter Embry, Michelle R. Mode of Action Classifications in the EnviroTox Database: Development and Implementation of a Consensus MOA Classification |
title | Mode of Action Classifications in the EnviroTox Database: Development and Implementation of a Consensus MOA Classification |
title_full | Mode of Action Classifications in the EnviroTox Database: Development and Implementation of a Consensus MOA Classification |
title_fullStr | Mode of Action Classifications in the EnviroTox Database: Development and Implementation of a Consensus MOA Classification |
title_full_unstemmed | Mode of Action Classifications in the EnviroTox Database: Development and Implementation of a Consensus MOA Classification |
title_short | Mode of Action Classifications in the EnviroTox Database: Development and Implementation of a Consensus MOA Classification |
title_sort | mode of action classifications in the envirotox database: development and implementation of a consensus moa classification |
topic | Hazard/Risk Assessment |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851772/ https://www.ncbi.nlm.nih.gov/pubmed/31269286 http://dx.doi.org/10.1002/etc.4531 |
work_keys_str_mv | AT kienzleraude modeofactionclassificationsintheenvirotoxdatabasedevelopmentandimplementationofaconsensusmoaclassification AT connorskristina modeofactionclassificationsintheenvirotoxdatabasedevelopmentandimplementationofaconsensusmoaclassification AT bonnellmark modeofactionclassificationsintheenvirotoxdatabasedevelopmentandimplementationofaconsensusmoaclassification AT barronmaceg modeofactionclassificationsintheenvirotoxdatabasedevelopmentandimplementationofaconsensusmoaclassification AT beasleyamy modeofactionclassificationsintheenvirotoxdatabasedevelopmentandimplementationofaconsensusmoaclassification AT ingliscristinag modeofactionclassificationsintheenvirotoxdatabasedevelopmentandimplementationofaconsensusmoaclassification AT norbergkingteresaj modeofactionclassificationsintheenvirotoxdatabasedevelopmentandimplementationofaconsensusmoaclassification AT martintodd modeofactionclassificationsintheenvirotoxdatabasedevelopmentandimplementationofaconsensusmoaclassification AT sandersonhans modeofactionclassificationsintheenvirotoxdatabasedevelopmentandimplementationofaconsensusmoaclassification AT vallottonnathalie modeofactionclassificationsintheenvirotoxdatabasedevelopmentandimplementationofaconsensusmoaclassification AT wilsonpeter modeofactionclassificationsintheenvirotoxdatabasedevelopmentandimplementationofaconsensusmoaclassification AT embrymicheller modeofactionclassificationsintheenvirotoxdatabasedevelopmentandimplementationofaconsensusmoaclassification |