U.S. Environmental Protection Agency Office of Research and Development EPA www.epa.gov < Proportions of categories observed in LC and GC. GC workflow: Katherine Phillips, Alice Yau (Southwest Labs) LC workflow: Alex Chao, Jon Sobus, Barbara Wetmore Risa R. Sayre1,2, John F. Wambaugh1, Katherine Phillips3, Antony Williams1, Christopher M. Grulke1 1) U.S. Environmental Protection Agency, Office of Research and Development, National Center for Computational Toxicology, RTP NC 2) Oak Ridge Institute of Science and Education (ORISE) Research Participant 3) U.S. Environmental Protection Agency, Office of Research and Development, National Exposure Research Laboratory, Computational Exposure Division, RTP NC 1) Background 2) Method: Categorizing chemical origin 5) Method: Supporting NTA identification 6) Discussion Risa R. Sayre l ORCID 0000-0002-6173-8020 l sayre.risa@epa.gov A public database supporting evidence-based exposomics To support identification of likely sources of chemicals found in biological media through non- targeted/suspect screening analysis (SSA/NTA), this work-in- progress annotates chemicals with likely origin categories and adds empirically-validated substance relationships between chemicals and their in vivo transformation products to the CompTox Chemicals Dashboard1. We identify five categories of chemical origin (based on Rappaport et al 20142) of small molecules found in human blood biomonitoring samples: 1) endogenous metabolome, 2a) exogenous nutrients, 2b) markers of exposure to exogenous nutrients, 3a) xenobiotics (pharmaceuticals, pesticides, and others), and 3b) markers of exposure to xenobiotics. 1) Williams AJ, et al. The CompTox Chemistry Dashboard: a community data resource for environmental chemistry. J Cheminform. 2017 Nov 28;9(1):61. 2) Rappaport SM, Barupal DK, Wishart D, Vineis P, Scalbert A. The Blood Exposome and Its Role in Discovering Causes of Disease. Environ Health Perspect. 2014 Aug; 122(8). 3) U.S. Food & Drug Administration. Substances Added to Food (formerly EAFUS). www.accessdata.fda.gov/scripts/fdcc/?set=FoodSubstances 4) U.S. EPA Office of Pesticide Programs. Pesticide Chemical Search. iaspub.epa.gov/apex/pesticides/f?p=chemicalsearch:1 5) U.S. EPA TSCA Chemical Substance Inventory. www.epa.gov/tsca-inventory/how-access-tsca-inventory 6) Sobus JR, et al. Integrating tools for non-targeted analysis research and chemical safety evaluations at the US EPA. J Expo Sci Environ Epidemiol. 2017 Dec 29. 7) Richard AM, Williams CR. Distributed structure-searchable toxicity (DSSTox) public database network: a proposal. Mutat Res. 2002 Jan 29;499(1):27-52. 8) U.S. EPA High Production Volume Information System. http://iaspub.epa.gov/oppthpv/hpv_hc_characterization.get_report?doctype=2 9) McEachran AD, Sobus JR, Williams AJ. Identifying known unknowns using the US EPA's CompTox Chemistry Dashboard. Anal Bioanal Chem. 2017 Mar;409(7):1729-1735. This project was supported in part by an appointment to the Internship/Research Participation Program at the National Center for Computational Toxicology, U.S. Environmental Protection Agency, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and EPA. 7) References Over 10,000 mappings of xenobiotic transformation relationships are being added to DSSTox, many of which are not currently registered in any metabolomics database. Developing methods to improve identification of these substances measured in human blood and their source categories supports active Agency research projects (e.g. for PFAS chemicals). Registration of xenobiotics and observed transformation products based on dose levels demonstrated to yield a detectable (by a known method) amount of product in a particular species and medium in a chemical library • allows development of exposure estimates • identifies candidate substances and pathways to inform future high- throughput assay research to identify