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Adverse Outcome Pathways to Support the Assessment of Chemical Mixtures

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Chemical Mixtures and Combined Chemical and Nonchemical Stressors

Abstract

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 toward the use of less costly alternative techniques. The adverse outcome pathway (AOP) concept has emerged as a scaffold for organizing mechanistic information from these methods. Two main elements – key events (KEs) and key event relationships (KERs) – are utilized 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 organization 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 risk assessment of chemical mixtures. The structure of the AOP provides much more precision when considering mechanistic data in a mixtures assessment. The use of this concept provides a means to allow more specificity when deciding whether to use dose addition, independent action or integrated addition risk assessment methodologies. Furthermore, AOPs enable novel approaches for determining chemical groups and how they may be utilized within mixtures risk assessment.

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Abbreviations

ADME:

Absorption, distribution, metabolism, and elimination

AO:

Adverse outcome

AOP:

Adverse outcome pathway

KE:

Key event

KER:

Key event relationship

MIE:

Molecular initiating event

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Acknowledgments

M.D.N. was supported by an appointment to the Research Participation Program of the U.S. Environmental Protection Agency, Office of Research and Development, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. EPA.

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Authors and Affiliations

  1. Oak Ridge Institute for Science and Education, Oak Ridge, TN, USA

    Mark D. Nelms

  2. Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA

    Mark D. Nelms, Jane Ellen Simmons & Stephen W. Edwards

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  1. Mark D. Nelms
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  2. Jane Ellen Simmons
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Correspondence to Jane Ellen Simmons .

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Editors and Affiliations

  1. National Toxicology Program, National Institute of Environmental, Health Sciences, Research Triangle Park, North Carolina, USA

    Cynthia V. Rider

  2. National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA

    Jane Ellen Simmons

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Nelms, M.D., Simmons, J.E., Edwards, S.W. (2018). Adverse Outcome Pathways to Support the Assessment of Chemical Mixtures. In: Rider, C., Simmons, J. (eds) Chemical Mixtures and Combined Chemical and Nonchemical Stressors. Springer, Cham. https://doi.org/10.1007/978-3-319-56234-6_7

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