Defining Molecular Initiating Events in the Adverse Outcome Pathway Framework for Risk Assessment
Chemical Research in Toxicology
American Chemical Society
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Allen, T., Goodman, J., Gutsell, S., & Russell, P. (2014). Defining Molecular Initiating Events in the Adverse Outcome Pathway Framework for Risk Assessment. Chemical Research in Toxicology, 27 2100-2112. https://doi.org/10.1021/tx500345j
Consumer and environmental safety decisions are based on exposure and hazard data, interpreted using risk assessment approaches. The adverse outcome pathway (AOP) conceptual framework has been presented as a logical sequence of events or processes within biological systems which can be used to understand adverse effects and refine current risk assessment practices in ecotoxicology. This framework can also be applied to human toxicology and is explored, based around investigating the molecular initiating events (MIEs) of compounds. The precise definition of the MIE has yet to reach general acceptance. In this work we present a unified MIE definition: an MIE is the initial interaction between a molecule and a biomolecule or biosystem that can be causally linked to an outcome via a pathway. Case studies are presented and issues with current definitions are addressed. With the development of a unified MIE definition the field can look towards defining, classifying and characterizing more MIEs, and using knowledge of the chemistry of these processes to aid AOP research and toxicity risk assessment. We also present the role of MIE research in the development of in vitro and in silico toxicology and suggest how, by using a combination of biological and chemical approaches, MIEs can be identified and characterized despite a lack of detailed reports, even for some of the most studied molecules in toxicology.
Molecular Initiating Event (MIE), Adverse Outcome Pathway (AOP), Human Toxicology, Risk Assessment
The authors acknowledge the financial support of Unilever.
External DOI: https://doi.org/10.1021/tx500345j
This record's URL: https://www.repository.cam.ac.uk/handle/1810/246404