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The role of omics in the application of adverse outcome pathways for chemical risk assessment
Citation:
Brockmeier, E., G. Hodges, T. Hutchinson, E. Butler, M. Hecker, K. Tollefsen, N. Garcia-Reyero, P. Kille, D. Becker, K. Chipman, J. Colbourne, Tim Collette, A. Cossins, M. Cronin, P. Graystock, S. Gutsell, D. Knapen, I. Katsiadaki, A. Lange, S. Marshall, S. Owen, E. Perkins, S. Plaistow, A. Schroeder, D. Taylor, M. Viant, G. Ankley, AND F. Falciani. The role of omics in the application of adverse outcome pathways for chemical risk assessment. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 158(2):252-262, (2017).
Impact/Purpose:
The purpose of the workshop described in this paper was to review the specific roles that high-content molecular-level omics datasets (e.g., transcriptomics, metabolomics, lipidomics and proteomics) can hold within the adverse outcome pathway (AOP) framework and for supporting risk assessments for both ecological and human health. In light of the growing number of examples of the application of omics data in the context of AOPs and ecological risk assessment, in this workshop we considered how omics datasets might continue to support the AOP framework. In particular, the role of AOPs in identifying potential Molecular Initiating Events (MIEs) and providing supportive evidence of Key Events (KEs) at different levels of biological organisation and across different taxonomic groups is discussed. Also addressed are areas with the strongest potential for short and medium-term breakthroughs, such as providing mechanistic evidence to support read-across, providing weight of evidence information for mode of action assignment, understanding biological networks, and developing more robust extrapolations of species-sensitivity. Key challenges are considered which need to be addressed, including the need for a cohesive experimental design approach, the lack of a mutually agreed framework to quantitatively link genes and pathways to KEs, and the need for better interpretation of chemically-induced molecular-level changes.
Description:
In conjunction with the second International Environmental Omics Symposium (iEOS) conference, held at the University of Liverpool (UK) in September 2014, we held a workshop to bring together toxicology and regulatory science experts from academia, government and industry. The purpose of the workshop was to review the specific roles that high-content molecular-level omics datasets (e.g., transcriptomics, metabolomics, lipidomics and proteomics) can hold within the adverse outcome pathway (AOP) framework and for supporting risk assessments for both ecological and human health. In light of the growing number of examples of the application of omics data in the context of AOPs and ecological risk assessment, in this workshop we considered how omics datasets might continue to support the AOP framework. In particular, we discuss the role of AOPs in identifying potential Molecular Initiating Events (MIEs) and providing supportive evidence of Key Events (KEs) at different levels of biological organisation and across different taxonomic groups. We also discuss areas with the strongest potential for short and medium-term breakthroughs, such as providing mechanistic evidence to support read-across, providing weight of evidence information for mode of action assignment, understanding biological networks, and developing more robust extrapolations of species-sensitivity. We consider the key challenges which need to be addressed, including the need for a cohesive experimental design approach, the lack of a mutually agreed framework to quantitatively link genes and pathways to KEs, and the need for better interpretation of chemically-induced molecular-level changes. This manuscript was developed to provide guidance for driving the long-awaited paradigm shift in how chemical and hazard assessments are conducted.
