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Using the aggregate exposure and adverse outcome pathways to create a taxonomy of chemical interactions relevant to the assessment of human health and environmental risks
Citation:
Price, P. AND J. Leonard. Using the aggregate exposure and adverse outcome pathways to create a taxonomy of chemical interactions relevant to the assessment of human health and environmental risks. 2019 Society of Toxicology Annual Meeting, Baltimore, MD, March 10 - 14, 2019.
Impact/Purpose:
The work is a novel taxonomy for organizing data on various types of chemical interactions that has a greater scope than existing frameworks on toxicological interactions of chemicals. The approach can organize data on interactions that occur over the entire source-exposure-response continuum. The proposed approach takes advantage of recent advances in the concepts of the aggregate exposure and the adverse outcome pathways. The taxonomy has the potential to better organize data on interactions between individual chemicals and to identify additional relationships and principles that can improve EPA's ability to predict and manage risks from multiple chemicals.
Description:
Understanding the impacts of concurrent chemical exposures on human health and the environment requires information on chemical interactions (the ability of one chemical to influence the effects of a second chemical). Chemicals interact through a variety of mechanisms. Aggregate Exposure Pathways (AEPs) organize mechanistic data on fate and transport, exposure, and dosimetry, while Adverse Outcome Pathways (AOPs) organize mechanistic data on toxicological effects. Together they provide a combined framework for defining causal events over the entire source-exposure-response continuum for a receptor (a person, non-human organism, or population). A taxonomy of chemical interactions is proposed that is based on the location in the continuum where a chemical interaction occurs. The taxonomy consists of a set of hierarchal categories defined using the nodes of the AEP-AOP framework. Four top-level and mutually-exclusive categories are defined as: 1) interactions that occur from the source to the external exposure surface (or boundary) of an organism; 2) interactions that occur from the surface to the target site exposure; 3) interactions that occur between the molecular initiating event (MIE) and the receptor’s adverse outcome (AO); and 4) interactions that only occur for population level AOs (i.e. ecological endpoints). Each category has multiple subcategories based on the types of interactions that occur on the relevant portion of the continuum. Categories 1 and 2 have subcategories for interactions involving; transport processes, transformation processes, and direct reactions between chemicals. Category 3 has subcategories for chemicals that interact through a common MIE, a common key event on an AOP, or a common AO (but with separate AOPs). Category 4 has subcategories based on direct and indirect interactions that cause an AO in a population of organisms. The categories and subcategories provide insights potentially useful in assessing the impact of chemical interactions on non-cancer risks, developing standardized definitions for interaction terms, and designing assays to predict the potential for interactions between specific chemicals. The views expressed in this presentation are those of the authors and do not reflect the views or policies of the U.S. EPA.
