Harnessing High-Throughput Monitoring Methods to Strengthen 21st Century Risk-Based Evaluations

Oral Presentation

Prepared by J. Sobus1, A. Williams2, A. Richard2, C. Grulke2, K. Mansouri3, B. Beverly3, J. Rager3, E. Ulrich, M. Strynar4
1 - USEPA Office of Research and Development, US EPA, RTP - 109 T.W. Alexander Drive, Durham, NC, 27709, United States
2 - National Center for Computational Toxicology, US EPA, Research Triangle Park, NC, United States
3 - Oak Ridge Institute for Science and Education (ORISE) Participant, Research Triangle Park, NC, , , United States
4 - National Exposure Research Laboratory, US EPA, RTP - 109 T.W. Alexander Drive, Durham, NC, 27709, United States

Contact Information: [email protected]; 919-541-2232


Over the past ten years, the US government has invested in high-throughput (HT) methods to screen chemicals for biological activity. Under the interagency Tox21 consortium and the US Environmental Protection Agency’s (EPA) ToxCast™ program, thousands of chemicals have been evaluated for bioactivity across hundreds of assays. While these efforts support hazard-based prioritizations, exposure-focused programs have also emerged (e.g., EPA’s ExpoCast™ program) to translate hazard data into risk-based decisions. This integrated screening framework offers an unprecedented means to improve chemical safety assessments in the US. Despite their obvious benefits, HT screening programs are not without challenges. The ToxCast program faces the daunting task of measuring bioactivity for thousands of registered chemicals while attempting to model activity for unknown numbers of potential biological metabolites and environmental transformation products – data are needed to help prioritize the larger universe of candidate chemicals for further testing. The ExpoCast program is developing efficient models to estimate potential exposures but lacks measurement data needed for parameterization and evaluation. This lack of measurement data, in both environmental and biological systems, often leads to large uncertainties in final exposure estimates. Clearly, HT chemical monitoring methods are needed to support ongoing efforts in the ToxCast and ExpoCast programs. Suspect screening and non-targeted analysis methods (SSA and NTA, respectively) are well suited to meet these needs, as they can rapidly generate measurement data for thousands of previously unstudied chemicals. Noting the opportunity to fill critical knowledge gaps, efforts are underway at EPA to develop, evaluate, and effectively use SSA and NTA workflows and data. As a reflection of these efforts, this presentation will highlight: 1) a framework for integrating SSA/NTA research within EPA’s ToxCast and ExpoCast programs; 2) results of a SSA case study that exploited ToxCast and ExpoCast data to identify emerging contaminants in house dust; and 3) software tools and databases being developed within EPA to support SSA/NTA activities across the broader research community. The goals of this presentation are to communicate EPA’s ongoing SSA/NTA research efforts and to foster discussion on the potential contributions of HT monitoring methods towards advancing 21st-century risk-based evaluations.