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Organizing mechanism-related information on chemical interactions using a framework based on the Aggregate Exposure and Adverse Outcome Pathways
Citation:
Price, P., A. Jarabek, AND L. Burgoon. Organizing mechanism-related information on chemical interactions using a framework based on the Aggregate Exposure and Adverse Outcome Pathways. ENVIRONMENT INTERNATIONAL. Elsevier B.V., Amsterdam, Netherlands, 138:105673, (2020). https://doi.org/10.1016/j.envint.2020.105673
Impact/Purpose:
Assessing risks from chemicals requires an understanding of how concurrent exposures to multiple chemicals can affect an individual's risks. While interactions between the toxicity of chemicals has been studied for more than 100 years, there is no single system for organizing data on chemical interactions. This paper proposed such a system. The system includes interactions that occur over the entire source-to-exposure-response continuum. The system may assist in the design of databases, information pipelines, and models of response that will support high throughput assessments of cumulative risk. This work builds on an earlier publication “Price, Paul, and Jeremy Leonard. "A proposal for creating a taxonomy of chemical interactions using concepts from the aggregate exposure and adverse outcome pathways." Current Opinion in Toxicology (2019).”
Description:
This paper presents a framework for organizing and accessing mechanistic data on chemical interactions to support the assessment of risks from combined chemical exposures. The framework allows the organizing of data on interactions between chemicals that occur over the entire source-to-outcome continuum including interactions that are studied in the fields of fate and transport, exposure assessment, dosimetry, and individual and population-based adverse outcomes. The framework proposes to organize data using a semantic triple of a chemical (subject), has impact (predicate), and a causal event on the source-to-outcome continuum of a second chemical (object). The location of the causal event on the source-to-outcome continuum and the nature of the impact are used as the basis for a taxonomy of interactions. The approach builds on concepts from the Aggerate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP). The framework proposes the linking of AEPs of multiple chemicals and the AOP networks relevant to those chemicals to form AEP-AOP networks that describe chemical interactions that cannot be characterized using AOP networks. Such AEP-AOP networks will aid the construction of workflows for both experimental design and risk assessments. Finally, the framework is used to link existing categories of mixture toxicology to specific categories of interactions.
URLs/Downloads:
DOI: Organizing mechanism-related information on chemical interactions using a framework based on the Aggregate Exposure and Adverse Outcome Pathways