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Screening for drinking water contaminants of concern using an automated exposure-focused workflow



The number of chemicals present in the environment exceeds the capacity of government bodies to characterize risk. Therefore, data-informed and reproducible processes are needed for identifying chemicals for further assessment. The Minnesota Department of Health (MDH), under its Contaminants of Emerging Concern (CEC) initiative, uses a standardized process to screen potential drinking water contaminants based on toxicity and exposure potential.


Recently, MDH partnered with the U.S. Environmental Protection Agency (EPA) Office of Research and Development (ORD) to accelerate the screening process via development of an automated workflow accessing relevant exposure data, including exposure new approach methodologies (NAMs) from ORD’s ExpoCast project.


The workflow incorporated information from 27 data sources related to persistence and fate, release potential, water occurrence, and exposure potential, making use of ORD tools for harmonization of chemical names and identifiers. The workflow also incorporated data and criteria specific to Minnesota and MDH’s regulatory authority. The collected data were used to score chemicals using quantitative algorithms developed by MDH. The workflow was applied to 1867 case study chemicals, including 82 chemicals that were previously manually evaluated by MDH.


Evaluation of the automated and manual results for these 82 chemicals indicated reasonable agreement between the scores although agreement depended on data availability; automated scores were lower than manual scores for chemicals with fewer available data. Case study chemicals with high exposure scores included disinfection by-products, pharmaceuticals, consumer product chemicals, per- and polyfluoroalkyl substances, pesticides, and metals. Scores were integrated with in vitro bioactivity data to assess the feasibility of using NAMs for further risk prioritization.


This workflow will allow MDH to accelerate exposure screening and expand the number of chemicals examined, freeing resources for in-depth assessments. The workflow will be useful in screening large libraries of chemicals for candidates for the CEC program.

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Fig. 1: Overview of the exposure screening workflow.
Fig. 2: Comparison of manual and automated scores.
Fig. 3: Exposure case study results.
Fig. 4: Bioactivity-to-exposure ratios for chemicals with high exposure scores.

Data availability

The results of the automated workflow for the case study chemicals and raw data values for each source and criteria are included in the Supplemental files.


  1. U. S. Environmental Protection Agency. White paper: Aquatic life criteria for contaminants of emerging concern. 2008. Accessed 15 Aug 2022.

  2. Yadav D, Rangabhashiyam S, Verma P, Singh P, Devi P, Kumar P, et al. Environmental and health impacts of contaminants of emerging concerns: Recent treatment challenges and approaches. Chemosphere. 2021;272:1–19.

    Article  Google Scholar 

  3. Kavlock R, Chandler K, Houck K, Hunter S, Judson R, Kleinstreuer N, et al. Update on EPA’s ToxCast program: providing high throughput decision support tools for chemical risk management. Chem Res Toxicol. 2012;25:1287–302.

    Article  CAS  PubMed  Google Scholar 

  4. Wambaugh JF, Bare JC, Carignan CC, Dionisio KL, Dodson RE, Jolliet O, et al. New approach methodologies for exposure science. Curr Opin Toxicol. 2019;15:76–92.

    Article  Google Scholar 

  5. Cohen Hubal EA, Richard A, Aylward L, Edwards S, Gallagher J, Goldsmith MR, et al. Advancing exposure characterization for chemical evaluation and risk assessment. J Toxicol Environ Health B Crit Rev. 2010;13:299–313.

    Article  CAS  PubMed  Google Scholar 

  6. U. S. Environmental Protection Agency. A proof-of-concept case study integrating publicly available information to screen candidates for chemical prioritization under TSCA. 2021. Accessed 15 Aug 2022.

  7. U. S. Environmental Protection Agency. Federal Insecticide, Fungicide, and Rodenticide Act Science Advisory Panel meeting - Endocrine activity and exposure-based prioritization and screening. 2014. Accessed 15 Aug 2022.

  8. Minnesota Department of Health. Contaminants of Emerging Concern (CEC) protecting Minnesota’s water resources. 2022. Accessed 17 Aug 2022.

  9. Minnesota Department of Health. Nominated contaminants status and information: MDH drinking water Contaminants of Emerging Concern (CEC) initiative. 2021. Accessed 15 Aug 2022.

  10. Williams AJ, Grulke CM, Edwards J, McEachran AD, Mansouri K, Baker NC, et al. The CompTox Chemistry Dashboard: a community data resource for environmental chemistry. J Cheminform. 2017;9:1–27.

    Article  Google Scholar 

  11. U. S. Environmental Protection Agency. Office of Water. Final Contaminant Candidate List 3 Chemicals: Classification of the PCCL to CCL. EPA 815-R-09-008. 2009. Accessed 15 Aug 2022.

  12. Mansouri K, Grulke CM, Judson RS, Williams AJ. OPERA models for predicting physicochemical properties and environmental fate endpoints. J Cheminfo. 2018;10:10.

    Article  Google Scholar 

  13. Isaacs KK, Glen WG, Egeghy P, Goldsmith MR, Smith L, Vallero D, et al. SHEDS-HT: an integrated probabilistic exposure model for prioritizing exposures to chemicals with near-field and dietary sources. Environ Sci Tech. 2014;48:12750–9.

    Article  CAS  Google Scholar 

  14. Ring CL, Arnot J, Bennett DH, Egeghy P, Fantke P, Huang L, et al. Consensus Modeling of Median Chemical Intake for the U.S. Population Based on Predictions of Exposure Pathways. Environ Sci Tech 2019;53:719–32.

    Article  CAS  Google Scholar 

  15. Isaacs KK, Wall JT, Williams AR, Hobbie KA, Sobus JR, Ulrich E, et al. A harmonized chemical monitoring database for support of exposure assessments. Sci Data. 2022;9:1–11.

  16. Sobus JR, Wambaugh JF, Isaacs KK, Williams AJ, McEachran AD, Richard AM, et al. Integrating tools for non-targeted analysis research and chemical safety evaluations at the US EPA. J Expo Sci Environ Epidemiol. 2018;28:411–26.

    Article  CAS  PubMed  Google Scholar 

  17. Grulke CM, Williams AJ, Thillanadarajah I, Richard AM. EPA’s DSSTox database: History of development of a curated chemistry resource supporting computational toxicology research. Comput Toxicol. 2019;12:1–15.

    Article  Google Scholar 

  18. U.S. Environmental Protection Agency. SHEDS-HT Beta Version 0.1.8. 2019. Accessed 15 Aug 2022.

  19. Wambaugh JF, Wang A, Dionisio KL, Frame A, Egeghy P, Judson R, et al. High throughput heuristics for prioritizing human exposure to environmental chemicals. Environ Sci Tech 2014;48:12760–7.

    Article  CAS  Google Scholar 

  20. Lowe CN, Phillips KA, Favela KA, Yau AY, Wambaugh JF, Sobus JR, et al. Chemical characterization of recycled consumer products using suspect screening analysis. Environ Sci Tech. 2021;55:11375–87.

    Article  CAS  Google Scholar 

  21. Phillips KA, Yau A, Fayela KA, Isaacs KK, McEachran A, Grulke C, et al. Suspect screening analysis of chemicals in consumer products. Environ Sci Tech 2018;52:3125–35.

    Article  CAS  Google Scholar 

  22. Dionisio KL, Phillips K, Price PS, Grulke CM, Williams AJ, Biryol D, et al. The Chemical and Products Database, a resource for exposure-relevant data on chemicals in consumer products. Sci Data. 2018;5:1–9.

    Article  Google Scholar 

  23. U. S. Environmental Protection Agency. 2016 Chemical Data Reporting Data Files. 2016. Accessed 15 Aug 2022.

  24. Minnesota Department of Agriculture. Minnesota Pesticide Sales Information. 2022. Accessed 15 Aug 2022.

  25. Mattingly CJ, Colby GT, Forrest JN, Boyer JL. The Comparative Toxicogenomics Database (CTD). Environ Health Perspect. 2003;111:793–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Paul Friedman K, Gagne M, Loo LH, Karamertzanis P, Netzeva T, Sobanski T, et al. Utility of in vitro bioactivity as a lower bound Estimate of in vivo adverse effect levels and in risk-based prioritization. Toxicol Sci. 2020;173:202–25.

    Article  PubMed  Google Scholar 

  27. Pearce RG, Setzer RW, Strope CL, Sipes NS, Wambaugh JF. httk: R Package for High-Throughput Toxicokinetics (HTTK). J Stat Softw. 2017;79:1–26.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Wetmore BA, Wambaugh JF, Ferguson SS, Sochaski MA, Rotroff DM, Freeman K, et al. Integration of dosimetry, exposure, and high-throughput screening data in chemical toxicity assessment. Toxicol Sci. 2012;125:157–74.

    Article  CAS  PubMed  Google Scholar 

  29. Wetmore BA, Wambaugh JF, Allen B, Ferguson SS, Sochaski MA, Setzer RW, et al. Incorporating high-throughput exposure predictions with dosimetry-adjusted in vitro bioactivity to inform chemical toxicity testing. Toxicol Sci. 2015;148:121–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. US Environmental Protection Agency. Center for Computational Toxicology and Exposure, EPA invitroDB v.3.4. 2021. Accessed 15 Aug 2022.

  31. Minnesota Department of Health. Human Health-Based Water Guidance Table. 2022. Accessed 15 Aug 2022.

  32. U.S. Environmental Protection Agency, CompTox Chemicals Dashboard List: Disinfection by-products (Richardson et al). 2022. Accessed 15 Aug 2022.

  33. U.S. Environmental Protection Agency, CompTox Chemicals Dashboard List: CATEGORY|PHARMACEUTICALS: DrugBank database from the University of Alberta. 2022. Accessed 15 Aug 2022.

  34. U.S. Environmental Protection Agency. CompTox Chemicals Dashboard List: NORMAN: List of PFAS from the OECD curated by Nikiforos Alygizakis. 2022. Accessed 15 Aug 2022.

  35. U.S. Environmental Protection Agency. CompTox Chemicals Dashboard List: PESTICIDES|EPA: List of active ingredients updated 10/25/2019. 2019. Available from: Accessed 15 Aug 2022.

  36. U.S. Environmental Protection Agency. CompTox Chemicals Dashboard List: PESTICIDES|EPA: List of inert ingredients food and nonfood use updated 10/25/2019. 2019. Accessed 15 Aug 2022.

  37. U.S. Environmental Protection Agency. CompTox Chemicals Dashboard List: CompTox Chemicals Dashboard List: WATER|EPA: Chemical contaminants - CCL 4. 2022. Accessed 15 Aug 2022.

  38. Phillips KA, Wambaugh JF, Grulke CM, Dionisio KL, Isaacs KK. High-throughput screening of chemicals as functional substitutes using structure-based classification models. Green Chem. 2017;19:1063–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Thomas RS, Bahadori T, Buckley TJ, Cowden J, Deisenroth C, Dionisio KL, et al. The Next Generation Blueprint of Computational Toxicology at the U.S. Environmental Protection Agency. Toxicol Sci. 2019;169:317–32.

    Article  CAS  PubMed  Google Scholar 

  40. Hopperstad K, DeGroot DE, Zurlinden T, Brinkman C, Thomas RS, Deisenroth C. Chemical screening in an estrogen receptor transactivation assay with metabolic competence. Toxicol Sci. 2022;187:112–26.

    Article  CAS  PubMed  Google Scholar 

  41. Deisenroth C, DeGroot DE, Zurlinden T, Eicher A, McCord J, Lee MY, et al. The alginate immobilization of metabolic enzymes platform retrofits an estrogen receptor transactivation assay with metabolic competence. Toxicol Sci. 2020;178:281–301.

    Article  CAS  PubMed  Google Scholar 

  42. DeGroot DE, Swank A, Thomas RS, Strynar M, Lee MY, Carmichael PL, et al. mRNA transfection retrofits cell-based assays with xenobiotic metabolism. J Pharm Toxicol Methods. 2018;92:77–94.

    Article  CAS  Google Scholar 

  43. Boyce M, Meyer B, Grulke C, Lizarraga L, Patlewicz G. Comparing the performance and coverage of selected in silico (liver) metabolism tools relative to reported studies in the literature to inform analogue selection in read-across: A case study. Comput Toxicol. 2022;21:1–15.

    Article  PubMed  PubMed Central  Google Scholar 

  44. McCord JP, Groff LC II, Sobus JR. Quantitative non-targeted analysis: Bridging the gap between contaminant discovery and risk characterization. Environ Int. 2022;158:1–12.

    Article  Google Scholar 

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The authors would like to thank Drs Peter Egeghy and Katherine Phillips of the US EPA for their technical review of this paper. The information in this document has been funded wholly or in part by the US Environmental Protection Agency. It does not signify that the contents necessarily reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. The paper has been subjected to the Agency’s review process and approved for publication.

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Authors and Affiliations



KKI designed workflow organization and data source integration, performed data analyses, and drafted figures, tables, and text. JTW designed and implemented workflow code, scoring algorithms, and reporting formats, and performed workflow runs. KPF performed bioactivity, toxicokinetic, and BER analyses and contributed associated text. AJW provided chemistry data support and contributed to text. JAF, ML, and JCL provided management support for the ORD/MDH CRADA project. AS provided management support for the workflow database and information technology infrastructure. KLD and JFW developed exposure and toxicokinetic NAM methods and datasets. HG, AJB, and CG of MDH developed the workflow criteria and scoring under the CEC program, provided manual scoring results, performed data analyses, and contributed to text.

Corresponding author

Correspondence to Kristin K. Isaacs.

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Isaacs, K.K., Wall, J.T., Paul Friedman, K. et al. Screening for drinking water contaminants of concern using an automated exposure-focused workflow. J Expo Sci Environ Epidemiol (2023).

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