Organizing mechanism-related information on chemical interactions using a framework based on the Aggregate Exposure and Adverse Outcome Pathways
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.