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Environmental surveillance and monitoring. The next frontiers for high-throughput toxicology
Citation:
Schroeder, A., G. Ankley, K. Houck, AND Dan Villeneuve. Environmental surveillance and monitoring. The next frontiers for high-throughput toxicology. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, 35(3):513-525, (2016).
Impact/Purpose:
Many of EPA’s program offices and regions are challenged with the task of assessing site specific hazards associated with in situ exposures of organisms to complex mixtures of contaminants present in the environment. Such assessments are challenging due to the relative lack of in-depth toxicological characterization for a large majority of chemicals present in the environment (often termed contaminants of emerging concern). Testing all potential mixtures is not a viable option. Consequently, there is a strong need for approaches that can use available pathway-based data from the peer-reviewed literature and emerging high throughput toxicology data sets to infer potential hazards that may be present at a site and identify appropriate endpoints and assays that could be used to monitor for those hazards. The present paper outlines three complementary strategies for utilizing 21st century toxicology tools, including high throughput data and assay platforms to identify the type(s) of bioactivity plausibly or empirically associated with a complex mixture. Those activities can then be linked to potential biological effects and hazards via the expanding adverse outcome pathway knowledge-base. This paper provides a conceptual overview of strategies being piloted and tested as part of ORD’s CSS research program (project 12.01, adverse outcome pathway discovery and development). If successful these strategies offer to transform mixture toxicology from an empirically-based strategy to a hypothesis-driven predictive approach which should be broadly applicable to a diverse range of sites and scenarios.
Description:
High throughput toxicity testing (HTT) technologies along with the world-wide web are revolutionizing both generation and access to data regarding the bioactivities that chemicals can elicit when they interact with specific proteins, genes, or other targets in the body of an organism. However, to date, most of the focus has been on the application of such data to assessment of individual chemicals. We suggest that environmental surveillance and monitoring represent the next frontiers for HTT. Resources already exist in curated databases of chemical-biological interactions, including highly standardized quantitative dose-response data generated from nascent HTT programs like ToxCast and Tox21, to link chemicals detected through environmental analytical chemistry to known biological activities. The emergence of the adverse outcome pathway framework and associated knowledgebase for linking molecular or pathway-level perturbations of biological systems to adverse outcomes traditionally considered in risk assessment and regulatory decision-making through a series of measureable biological changes provides a critical link between activity and hazard. Furthermore, environmental samples can be directly analyzed via HTT platforms to provide an unprecedented breadth of biological activity characterization that integrates the effects of all compounds present in a mixture, whether known or not. Novel application of these chemical-biological interaction data provide an opportunity to transform scientific characterization of potential hazards associated with exposure to complex mixtures of environmental contaminants.
