Characterizing pathways of exposure for risk-based chemical prioritization Data streams Large public inventories, reporting chemical use and/or occurrence: • ACToR USEdb [3]: manually-curated pathways database (2015) • CompTox Chemicals Dashboard (CCD) chemical lists [4] (https://comptox.epa.gov/dashboard/chemical-lists) • Chemical Data Reporting 2016-2020 [5] • CPDat (Chemical & Products Database) [6-11] via ChemExpo (see poster P284/abstract 3795) • Chemical-Product Composition data • Functional Use categories • Chemical List Presence (curated tags) Data streams include 62,692 unique DSSTox Substance IDs Figure 2. Data streams for food-only chemicals. Left panels: Specific CCD lists. Upper/lower panels: Chemicals with multiple/single data streams. Many chemicals have info only from CCD lists of food volatiles or food contact substances. https://comptox.epa.gov /dashboard/chemical- lists Case Study: Food-Only Chemicals For references or copy of poster: Scan QR code or https://github.com/carolinering/pathwaysSOT2023 Contact: ring.caroline@epa.gov Caroline L. Ring1; Paul M. Kruse1,2; John F. Wambaugh1; Kristin K. Isaacs1 1 US EPA Center for Computational Toxicology and Exposure (Research Triangle Park, NC, USA) 2 Oak Ridge Institute for Science and Education (Oak Ridge, TN, USA) Pathway classifications Figure 1. Heatmap of pathway classifications (left panel) and data stream sources (right panel) for 62,692 unique DTXSIDs. Overview Manual mapping of chemical exposure data to broad exposure pathway categories to categorize 62,692 chemicals by exposure pathway Methods Scientific Impact & Potential Applications • Pathways can be used to inform rapid exposure models for use in risk-based chemical prioritization [1], e.g.: • as a training set for automated read-across of exposure pathways based on chemical structure • as features (predictor variables) for machine-learning models of exposure [2] Consumer o Fragrance o Personal care o Cosmetic Pesticide o active o inert Industrial Pharmaceutical Food/Dietary Other o Flame retardant o Tobacco o Colorant o Commercial o Agricultural  Fertilizer o Biocide  Herbicide  Antimicrobial Chemical may be positive, negative, or unclassified (no data, NA) for each pathway. Negative = ChemExpo Chemical List Presence tags "prohibited", "restricted", "not used", "non_food_use", "nondetect" Classifications from each data stream may disagree. Here: • Any positive = positive overall. • No positive & any negative = negative overall. • All NA = NA overall. 6583 chemicals positive for the Food pathway and negative or NA for all other pathways Case Study Summary • Transparent, granular sourcing for pathway categorization • Majority of food-only chemicals rely on data from 1-2 lists • Food-only chemical classes are consistent with source lists (e.g. flavors) Figure 3. ClassyFire classifications for food-only chemicals. Colored rings: # of food-only chemicals in each superclass (inner ring) and class (outer ring, labels). Most frequent classes: Prenol lipids; Fatty acyls; Organooxygen compounds. Visualized using ClassyFire [12] & treecompareR package (see poster P160/abstract 3675). Fatty acyls Prenol lipids Organooxygen cpds.