The role of omics in the application of adverse outcome pathways for chemical risk assessment

Erica K. Brockmeier, Geoff Hodges, Thomas H. Hutchinson, Emma Butler, Markus Hecker, Knut Erik Tollefsen, Natalia Garcia-Reyero, Peter Kille, Dörthe Becker, Kevin Chipman, John Colbourne, Timothy W. Collette, Andrew Cossins, Mark Cronin, Peter Graystock, Steve Gutsell, Dries Knapen, Ioanna Katsiadaki, Anke Lange, Stuart MarshallStewart F. Owen, Edward J. Perkins, Stewart Plaistow, Anthony Schroeder, Daisy Taylor, Mark Viant, Gerald Ankley, Francesco Falciani

    Research output: Contribution to journalArticlepeer-review

    62 Scopus citations

    Abstract

    In conjunction with the second International Environmental Omics Symposium (iEOS) conference, held at the University of Liverpool (United Kingdom) in September 2014, a workshop was held to bring together experts in toxicology and regulatory science from academia, government and industry. The purpose of the workshop was to review the specific roles that high-content omics datasets (eg, transcriptomics, metabolomics, lipidomics, and proteomics) can hold within the adverse outcome pathway (AOP) framework for supporting ecological and human health risk assessments. In light of the growing number of examples of the application of omics data in the context of ecological risk assessment, we considered how omics datasets might continue to support the AOP framework. In particular, the role of omics in identifying potential AOP molecular initiating events and providing supportive evidence of key events at different levels of biological organization and across taxonomic groups was discussed. Areas with potential for short and medium-term breakthroughs were also discussed, such as providing mechanistic evidence to support chemical read-across, providing weight of evidence information for mode of action assignment, understanding biological networks, and developing robust extrapolations of species-sensitivity. Key challenges that need to be addressed were considered, including the need for a cohesive approach towards experimental design, the lack of a mutually agreed framework to quantitatively link genes and pathways to key events, and the need for better interpretation of chemically induced changes at the molecular level. This article was developed to provide an overview of ecological risk assessment process and a perspective on how high content molecular-level datasets can support the future of assessment procedures through the AOP framework.

    Original languageEnglish (US)
    Article numberkfx097
    Pages (from-to)252-262
    Number of pages11
    JournalToxicological Sciences
    Volume158
    Issue number2
    DOIs
    StatePublished - Aug 1 2017

    Bibliographical note

    Funding Information:
    The content of this article is based on the discussions and conclusions made as part of an international expert workshop, “Potential Roles of Omics Data in the use of Adverse Outcome Pathways for Environmental Risk Assessment”, which was held at the University of Liverpool (Liverpool, UK) on September 18th, 2014. Financial support for the workshop was provided by Unilever and was partially supported by a Natural Environment Research Council (NERC) Grant (NE/1028246/2) awarded to Francesco Falciani. The authors would like to acknowledge conference and workshop organising committee member Louise Crompton. All workshop attendees and co-authors approved and contributed to the final version of this manuscript. Opinions, interpretations, conclusions, and recommendations are those of the author(s) and are not necessarily endorsed by the US Environmental Protection Agency or US Army.

    Keywords

    • In vitro and alternatives
    • Methods
    • Predictive toxicology
    • Regulatory/policy
    • Risk assessment
    • Toxicogenomics

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