For years, low-throughput testing strategies have struggled to keep pace with demands of regulatory programs that are designed to ensure chemical safety and protect public health. Recently, high-throughput in vitro and in silico methods have been utilized by the U.S. Environmental Protection Agency (EPA) to help prioritize chemicals based on potential human and ecological health risks. Specifically, bioactivity estimates from EPA’s Toxicity Forecaster (ToxCast) project, combined with exposure estimates from EPA’s Exposure Forecaster (ExpoCast) project, have helped identify chemicals in need of higher-tier testing. To date, thousands of chemicals have been screened via the ToxCast and ExpoCast projects. Yet, needs still exist for screening-level data on previously untested parent chemicals, environmental degradants, biological metabolites, and chemical mixtures. Furthermore, analytical chemistry data are required to evaluate existing model-based predictions. Targeted analytical chemistry methods are unable to meet these needs, as they are generally utilized for quantitative analysis of limited “known” compounds. Non-targeted analysis (NTA) methods, however, are well-suited to support high-throughput screening (HTS) programs, as they rapidly generate data for thousands of compounds without a priori knowledge of compounds of interest. Noting this inherent benefit, we developed an integrated research framework, wherein NTA directly supports HTS programs, and also makes use of existing bioactivity and exposure data. This research integration is made possible via EPA’s CompTox Chemistry Dashboard, a freely accessible web-based application and data hub. Utilization of the framework at EPA for environmental and biological analyses are underway. In parallel, EPA’s Non-Targeted Analysis Collaborative Trial (ENTACT) has been launched, and will serve as a means to establish benchmark NTA methods for the research community. This presentation will review EPA’s HTS research programs, introduce the integrated research framework and supporting tools, describe pilot-study applications of the framework, and summarize current and planned activities related to ENTACT.

Integrating non-targeted analysis research with high-throughput chemical screening programs at the US EPA

254th National Meeting (2017)

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