摘要：This paper presents a framework for organizing and accessing mechanistic data on chemical interactions. The framework is designed to support the assessment of risks from combined chemical exposures. The framework covers interactions between chemicals that occur over the entire source-to-outcome continuum including interactions that are studied in the fields of chemical transport, environmental fate, 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 also builds on concepts from the Aggregate 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 alone. Such AEP-AOP networks will aid the construction of workflows for both experimental design and the systematic review or evaluation performed in risk assessments. Finally, the framework is used to link the constructs of existing component-based approaches for mixture toxicology to specific categories in the interaction taxonomy.
关键词：Chemical interactions ; Mixture toxicity ; Adverse outcome pathway ; Aggregate exposure pathway ; ADME absorptiondistributionmetabolism and elimination ; AEP Aggregate Exposure Pathway ; AO Adverse Outcome ; AOP Adverse Outcome Pathway ; CSM Conceptual Site Model ; ICKE Initial Common Key Event ; KE Key Event ; KER Key Event Relationship ; KES Key Exposure State ; KTR Key Transition Rate ; MIE Molecular Initiating Event ; NAM New Approach Methodology ; RDF Resource Description Framework ; TSE Target Site Exposure ; qAOP quantitative Adverse Outcome Pathway
