Adverse outcome pathway networks I: Development and applications

Dries Knapen; Michelle M. Angrish; Marie C. Fortin; Ioanna Katsiadaki; Marc Leonard; Luigi Margiotta-Casaluci; Sharon Munn; Jason M. O'Brien; Nathan Pollesch; L. Cody Smith; Xiaowei Zhang; Daniel L. Villeneuve

doi:10.1002/etc.4125

Adverse outcome pathway networks I: Development and applications

Dries Knapen^*, Michelle M. Angrish, Marie C. Fortin, Ioanna Katsiadaki, Marc Leonard, Luigi Margiotta-Casaluci, Sharon Munn, Jason M. O'Brien, Nathan Pollesch, L. Cody Smith, Xiaowei Zhang, Daniel L. Villeneuve

^*Corresponding author for this work

Analytical, Environmental & Forensic Sciences

Research output: Contribution to journal › Article › peer-review

188 Citations (Scopus)

Abstract

Based on the results of a Horizon Scanning exercise sponsored by the Society of Environmental Toxicology and Chemistry that focused on advancing the adverse outcome pathway (AOP) framework, the development of guidance related to AOP network development was identified as a critical need. This not only included questions focusing directly on AOP networks, but also on related topics such as mixture toxicity assessment and the implementation of feedback loops within the AOP framework. A set of two articles has been developed to begin exploring these concepts. In the present article (part I), we consider the derivation of AOP networks in the context of how it differs from the development of individual AOPs. We then propose the use of filters and layers to tailor AOP networks to suit the needs of a given research question or application. We briefly introduce a number of analytical approaches that may be used to characterize the structure of AOP networks. These analytical concepts are further described in a dedicated, complementary article (part II). Finally, we present a number of case studies that illustrate concepts underlying the development, analysis, and application of AOP networks. The concepts described in the present article and in its companion article (which focuses on AOP network analytics) are intended to serve as a starting point for further development of the AOP network concept, and also to catalyze AOP network development and application by the different stakeholder communities. Environ Toxicol Chem 2018;37:1723–1733.

Original language	English
Pages (from-to)	1723-1733
Number of pages	11
Journal	ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY
Volume	37
Issue number	6
DOIs	https://doi.org/10.1002/etc.4125
Publication status	Published - Jun 2018

Keywords

Adverse outcome pathway
Adverse outcome pathway network
Network development
Network topology
Predictive toxicology
Risk assessment

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10.1002/etc.4125

Cite this

@article{1530076f72b946a0a79ceb38b67b8af5,

title = "Adverse outcome pathway networks I: Development and applications",

abstract = "Based on the results of a Horizon Scanning exercise sponsored by the Society of Environmental Toxicology and Chemistry that focused on advancing the adverse outcome pathway (AOP) framework, the development of guidance related to AOP network development was identified as a critical need. This not only included questions focusing directly on AOP networks, but also on related topics such as mixture toxicity assessment and the implementation of feedback loops within the AOP framework. A set of two articles has been developed to begin exploring these concepts. In the present article (part I), we consider the derivation of AOP networks in the context of how it differs from the development of individual AOPs. We then propose the use of filters and layers to tailor AOP networks to suit the needs of a given research question or application. We briefly introduce a number of analytical approaches that may be used to characterize the structure of AOP networks. These analytical concepts are further described in a dedicated, complementary article (part II). Finally, we present a number of case studies that illustrate concepts underlying the development, analysis, and application of AOP networks. The concepts described in the present article and in its companion article (which focuses on AOP network analytics) are intended to serve as a starting point for further development of the AOP network concept, and also to catalyze AOP network development and application by the different stakeholder communities. Environ Toxicol Chem 2018;37:1723–1733.",

keywords = "Adverse outcome pathway, Adverse outcome pathway network, Network development, Network topology, Predictive toxicology, Risk assessment",

author = "Dries Knapen and Angrish, {Michelle M.} and Fortin, {Marie C.} and Ioanna Katsiadaki and Marc Leonard and Luigi Margiotta-Casaluci and Sharon Munn and O'Brien, {Jason M.} and Nathan Pollesch and Smith, {L. Cody} and Xiaowei Zhang and Villeneuve, {Daniel L.}",

note = "Funding Information: Acknowledgment—We gratefully acknowledge the Society of Environmental Toxicology and Chemistry (SETAC) North America staff, in particular G. Schiefer, N. Mayo, and T. Schlekat, who provided support to the workshop co-chairs, steering committee, and participants before, during, and after the workshop. We appreciate funding support from SETAC, the US Environmental Protection Agency, the American Cleaning Institute, the European Chemical Industry Council Long-Range Research Initiative, Chevron Environmental, the European Center for Ecotoxicology and Toxicology of Chemicals, the European Commission Joint Research Centre, European Crop Protection Association, ExxonMobil, Humane Society International, The Humane Society of the United States, the Human Toxicology Project Consortium, Syngenta, and Unilever. In addition, we thank the groups from academia, industry, and government who supported participants{\textquoteright} travel. The authors thank the workshop co-chairs, C. LaLone and M. Hecker, for their coordination, organization, and guidance. We acknowledge the other workshop participants for their stimulating discussions and feedback, and the respondents to the Horizon Scanning effort for the charge questions and themes that informed our discussion. Publisher Copyright: {\textcopyright} 2018 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc.",

year = "2018",

month = jun,

doi = "10.1002/etc.4125",

language = "English",

volume = "37",

pages = "1723--1733",

journal = "ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY",

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T1 - Adverse outcome pathway networks I

T2 - Development and applications

AU - Knapen, Dries

AU - Angrish, Michelle M.

AU - Fortin, Marie C.

AU - Katsiadaki, Ioanna

AU - Leonard, Marc

AU - Margiotta-Casaluci, Luigi

AU - Munn, Sharon

AU - O'Brien, Jason M.

AU - Pollesch, Nathan

AU - Smith, L. Cody

AU - Zhang, Xiaowei

AU - Villeneuve, Daniel L.

N1 - Funding Information: Acknowledgment—We gratefully acknowledge the Society of Environmental Toxicology and Chemistry (SETAC) North America staff, in particular G. Schiefer, N. Mayo, and T. Schlekat, who provided support to the workshop co-chairs, steering committee, and participants before, during, and after the workshop. We appreciate funding support from SETAC, the US Environmental Protection Agency, the American Cleaning Institute, the European Chemical Industry Council Long-Range Research Initiative, Chevron Environmental, the European Center for Ecotoxicology and Toxicology of Chemicals, the European Commission Joint Research Centre, European Crop Protection Association, ExxonMobil, Humane Society International, The Humane Society of the United States, the Human Toxicology Project Consortium, Syngenta, and Unilever. In addition, we thank the groups from academia, industry, and government who supported participants’ travel. The authors thank the workshop co-chairs, C. LaLone and M. Hecker, for their coordination, organization, and guidance. We acknowledge the other workshop participants for their stimulating discussions and feedback, and the respondents to the Horizon Scanning effort for the charge questions and themes that informed our discussion. Publisher Copyright: © 2018 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc.

PY - 2018/6

Y1 - 2018/6

N2 - Based on the results of a Horizon Scanning exercise sponsored by the Society of Environmental Toxicology and Chemistry that focused on advancing the adverse outcome pathway (AOP) framework, the development of guidance related to AOP network development was identified as a critical need. This not only included questions focusing directly on AOP networks, but also on related topics such as mixture toxicity assessment and the implementation of feedback loops within the AOP framework. A set of two articles has been developed to begin exploring these concepts. In the present article (part I), we consider the derivation of AOP networks in the context of how it differs from the development of individual AOPs. We then propose the use of filters and layers to tailor AOP networks to suit the needs of a given research question or application. We briefly introduce a number of analytical approaches that may be used to characterize the structure of AOP networks. These analytical concepts are further described in a dedicated, complementary article (part II). Finally, we present a number of case studies that illustrate concepts underlying the development, analysis, and application of AOP networks. The concepts described in the present article and in its companion article (which focuses on AOP network analytics) are intended to serve as a starting point for further development of the AOP network concept, and also to catalyze AOP network development and application by the different stakeholder communities. Environ Toxicol Chem 2018;37:1723–1733.

AB - Based on the results of a Horizon Scanning exercise sponsored by the Society of Environmental Toxicology and Chemistry that focused on advancing the adverse outcome pathway (AOP) framework, the development of guidance related to AOP network development was identified as a critical need. This not only included questions focusing directly on AOP networks, but also on related topics such as mixture toxicity assessment and the implementation of feedback loops within the AOP framework. A set of two articles has been developed to begin exploring these concepts. In the present article (part I), we consider the derivation of AOP networks in the context of how it differs from the development of individual AOPs. We then propose the use of filters and layers to tailor AOP networks to suit the needs of a given research question or application. We briefly introduce a number of analytical approaches that may be used to characterize the structure of AOP networks. These analytical concepts are further described in a dedicated, complementary article (part II). Finally, we present a number of case studies that illustrate concepts underlying the development, analysis, and application of AOP networks. The concepts described in the present article and in its companion article (which focuses on AOP network analytics) are intended to serve as a starting point for further development of the AOP network concept, and also to catalyze AOP network development and application by the different stakeholder communities. Environ Toxicol Chem 2018;37:1723–1733.

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KW - Adverse outcome pathway network

KW - Network development

KW - Network topology

KW - Predictive toxicology

KW - Risk assessment

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ER -

Adverse outcome pathway networks I: Development and applications

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Keywords

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