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Environmental surveillance and monitoring the next frontier for pathway-based high throughput screening
Citation:
Villeneuve, Dan. Environmental surveillance and monitoring the next frontier for pathway-based high throughput screening. International Chemical Congress of Pacific Basin Societies (Pacifichem), Honolulu, HI, December 15 - 20, 2015.
Impact/Purpose:
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Description:
In response to a proposed vision and strategy for toxicity testing in the 21st century nascent high throughput toxicology (HTT) programs have tested thousands of chemicals in hundreds of pathway-based biological assays. Although, to date, use of HTT data for safety assessment of individual chemicals has been the focus, these same HTS approaches and data have potential to transform the way we conduct environmental surveillance and monitoring. The steadily growing database of HTT results can be mined to identify specific, toxicologically relevant, bioactivities that are associated with chemicals detected in the environment through analytical chemistry approaches. Calculation of exposure:activity ratios (EARs) that measured chemical concentrations with in vitro effect concentrations can be used to rank chemicals relative to their likelihood of causing biological responses in exposed organisms, allowing them to be prioritized for subsequent study, monitoring, and/or source identification. Likewise, EARs can be used to elucidate the specific bioactivities most likely to be associated with exposure at a given site. By mapping these bioactivities to established adverse outcome pathways (AOPs), both hazards of potential concern and suitable biological endpoints for effects-based monitoring can be identified. Finally, HTT approaches can be applied directly to screen complex mixtures of contaminants, extracted from environmental samples, for relevant bioactivities. This provides an integrated measure of biological activities that can account for both detected and unknown contaminants. These approaches can facilitate unprecedented ability to connect chemical concentrations in the environment with potential biological effects and facilitate hypothesis-driven approaches to environmental monitoring and risk assessment.