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Adverse Outcome Pathway ‘Footprinting’: A Novel Approach to the Integration of 21st Century Toxicology Information into Chemical Mixtures Risk Assessment

For over a decade, New Approach Methodologies (NAMs) such as structure-activity/read-across, -omics technologies, and Adverse Outcome Pathway (AOP), have been considered within regulatory communities as alternative sources of chemical and biological information potentially relevant to human health r...

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Autor principal: Lambert, Jason C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9860797/
https://www.ncbi.nlm.nih.gov/pubmed/36668763
http://dx.doi.org/10.3390/toxics11010037
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author Lambert, Jason C.
author_facet Lambert, Jason C.
author_sort Lambert, Jason C.
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description For over a decade, New Approach Methodologies (NAMs) such as structure-activity/read-across, -omics technologies, and Adverse Outcome Pathway (AOP), have been considered within regulatory communities as alternative sources of chemical and biological information potentially relevant to human health risk assessment. Integration of NAMs into applications such as chemical mixtures risk assessment has been limited due to the lack of validation of qualitative and quantitative application to adverse health outcomes in vivo, and acceptance by risk assessors. However, leveraging existent hazard and dose–response information, including NAM-based data, for mixture component chemicals across one or more levels of biological organization using novel approaches such as AOP ‘footprinting’ proposed herein, may significantly advance mixtures risk assessment. AOP footprinting entails the systematic stepwise profiling and comparison of all known or suspected AOPs involved in a toxicological effect at the level of key event (KE). The goal is to identify key event(s) most proximal to an adverse outcome within each AOP suspected of contributing to a given health outcome at which similarity between mixture chemicals can be confidently determined. These key events are identified as the ‘footprint’ for a given AOP. This work presents the general concept, and a hypothetical example application, of AOP footprinting as a key methodology for the integration of NAM data into mixtures risk assessment.
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spelling pubmed-98607972023-01-22 Adverse Outcome Pathway ‘Footprinting’: A Novel Approach to the Integration of 21st Century Toxicology Information into Chemical Mixtures Risk Assessment Lambert, Jason C. Toxics Article For over a decade, New Approach Methodologies (NAMs) such as structure-activity/read-across, -omics technologies, and Adverse Outcome Pathway (AOP), have been considered within regulatory communities as alternative sources of chemical and biological information potentially relevant to human health risk assessment. Integration of NAMs into applications such as chemical mixtures risk assessment has been limited due to the lack of validation of qualitative and quantitative application to adverse health outcomes in vivo, and acceptance by risk assessors. However, leveraging existent hazard and dose–response information, including NAM-based data, for mixture component chemicals across one or more levels of biological organization using novel approaches such as AOP ‘footprinting’ proposed herein, may significantly advance mixtures risk assessment. AOP footprinting entails the systematic stepwise profiling and comparison of all known or suspected AOPs involved in a toxicological effect at the level of key event (KE). The goal is to identify key event(s) most proximal to an adverse outcome within each AOP suspected of contributing to a given health outcome at which similarity between mixture chemicals can be confidently determined. These key events are identified as the ‘footprint’ for a given AOP. This work presents the general concept, and a hypothetical example application, of AOP footprinting as a key methodology for the integration of NAM data into mixtures risk assessment. MDPI 2022-12-30 /pmc/articles/PMC9860797/ /pubmed/36668763 http://dx.doi.org/10.3390/toxics11010037 Text en © 2022 by the author. 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
Lambert, Jason C.
Adverse Outcome Pathway ‘Footprinting’: A Novel Approach to the Integration of 21st Century Toxicology Information into Chemical Mixtures Risk Assessment
title Adverse Outcome Pathway ‘Footprinting’: A Novel Approach to the Integration of 21st Century Toxicology Information into Chemical Mixtures Risk Assessment
title_full Adverse Outcome Pathway ‘Footprinting’: A Novel Approach to the Integration of 21st Century Toxicology Information into Chemical Mixtures Risk Assessment
title_fullStr Adverse Outcome Pathway ‘Footprinting’: A Novel Approach to the Integration of 21st Century Toxicology Information into Chemical Mixtures Risk Assessment
title_full_unstemmed Adverse Outcome Pathway ‘Footprinting’: A Novel Approach to the Integration of 21st Century Toxicology Information into Chemical Mixtures Risk Assessment
title_short Adverse Outcome Pathway ‘Footprinting’: A Novel Approach to the Integration of 21st Century Toxicology Information into Chemical Mixtures Risk Assessment
title_sort adverse outcome pathway ‘footprinting’: a novel approach to the integration of 21st century toxicology information into chemical mixtures risk assessment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9860797/
https://www.ncbi.nlm.nih.gov/pubmed/36668763
http://dx.doi.org/10.3390/toxics11010037
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