Citation:

Nelms, M., J. Simmons, AND S. Edwards. Adverse Outcome Pathways to Support the Assessment of Chemical Mixtures. Chapter 7, Chemical Mixtures and Combined Chemical and Nonchemical Stressors: Exposure, Toxicity, Analysis and Risk. Springer, New York, NY, , 177-201, (2018). https://doi.org/10.1007/978-3-319-56234-6_7

Impact/Purpose:

Adverse Outcome Pathways (AOPs) can inform risk assessment involving chemical mixtures by providing a structured description of the mechanisms underlying the chemical toxicity. In the short term, this information can provide additional confidence in decisions regarding whether a dose addition or independent action assumption should be made. In the longer term, the AOP can be used to identify intermediate key events as surrogates for the adverse outcome in cases where independent action is required. The AOP can also be used to identify key events that could be used to evaluate dose addition assumptions where the confidence in that choice is not sufficient for the decision context. This book chapter reviews the AOP concept for scientist working on chemical mixtures and discusses the potential uses for AOPs in this context.

Description:

Due to the ever-increasing number of chemicals coming to market, and the cost of performing traditional in vivo studies, there has been a shift towards the use of less costly alternative techniques. The adverse outcome pathway (AOP) concept has emerged as a scaffold for organising mechanistic information from these methods. Two main elements – key events (KE) and key event relationships (KER) – are utilised to describe the underlying mechanism outlined by the AOP. Each KE depicts the measureable changes in the state of the biological system at each level of organisation that are essential for the progression along the pathway. The KERs, meanwhile, contain the biological information that connects each of the KEs. This chapter covers some of the potential applications for AOPs when performing cumulative risk assessment of chemical mixtures. The structure of the AOP provides more precision when considering mechanistic data in a mixtures assessment. Use of this concept provides a means to allow more specificity when deciding whether to perform dose addition or independent action. Furthermore, AOPs enable novel approaches for determining chemical groups and how they may be utilised in a mixtures risk assessment context.

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