Accessing Data to Support Pesticide Residue and Emerging Contaminant Analysis from US-EPA Online Dashboards

In recent years, the growth of scientific data and the increasing need for data sharing and collaboration in the field of environmental chemistry has led to the creation of various software and databases that facilitate research and development into the safety and toxicity of chemicals. The US-EPA Center for Computational Toxicology and Exposure has been developing software and databases that serve the chemistry community for many years. This presentation will focus on several web-based software applications which have been developed at the USEPA and made available to the community. While the primary software application from the Center is the CompTox Chemicals Dashboard which provides access to data for >1.2 million chemicals (https://comptox.epa.gov/dashboard), almost a dozen proof-of-concept applications have been built serving various capabilities. The publicly accessible proof-of-concept Cheminformatics Modules (https://www.epa.gov/chemicalresearch/cheminformatics) provides access to multiple applications in development allowing for hazard comparison for sets of chemicals, structure-substructure-similarity searching, structure alerts and batch QSAR prediction of both physicochemical and toxicity endpoints. A number of other applications, presently in development but not publicly accessible will also be discussed. These include AMOS, the database of Analytical Methods and Open Spectra.
Analytical methods can vary in nature from detailed regulatory methods to more summary in nature. Regulatory method documents can include details of analytes which can be studied, supported matrices, reagents, methodological details, statistical performance, interlaboratory validation and other details. Summary methods provide a general overview of reagents, instrumentation and commonly a short list of analytes. Regulatory bodies including the US Environmental Protection Agency (US-EPA), US Geological Survey (USGS), US Department of Agriculture (USDA) and others provide detailed analytical methods and collections of summary methods from the agrochemical industry, such as the US-EPA Environmental Chemistry Methods (https://www.epa.gov/pesticide-analytical-methods/environmental-chemistry-methods-ecm). Instrument vendors also provide access to many hundreds of application notes which can be considered as summary methods. AMOS presently contains >4,500 methods integrated to their chemical structures and > 230,000 public domain mass spectral data. AMOS allows for filtering of methods based on analyte, chemical class, method source and other related metadata. AMOS is an important facet of the developing Non-Targeted Analysis WebApp presently also in development at the EPA.
This presentation will provide an overview of existing publicly accessible Dashboards and work in progress to support analysis of pesticides, veterinary drug residues, and other chemicals in food, animal feed, and environmental samples.

1. The views expressed in this presentation are those of the author and do not necessarily reflect the views or policies of the U.S. EPA Accessing Data to Support Pesticide Residue and Emerging Contaminant Analysis from US-EPA Online Dashboards Antony Williams North American Chemical Residue Workshop: July 2024

2. US EPA: Office of Research and Development Office of Research and Development (ORD) is the research arm of EPA Public health and environmental assessment Computational toxicology, exposure & modeling I work for the Center for Computational Toxicology and Exposure in the Computational Chemistry and Cheminformatics Branch

3. Free-Access Cheminformatics Tools The Center for Computational Toxicology and Exposure has delivered many tools including CompTox Chemicals Dashboard (primary tool from the center) Proof-of-Concept cheminformatics modules Chemicals Hazard Profiling Chemical Transformations Database Analytical Methods and Spectra Chemical Safety Profiling 2

4. Research Projects we apply them to

5. 4 Research Projects we apply them to

6. Research Projects we apply them to

7. 6 Research Projects we apply them to

8. Curating Chemistry into the DSSTox Database 7 Chemistry underpins all of our tools Data assembly and curation is critical DSSTox assembled over 25 years

9. CompTox Chemicals Dashboard https://comptox.epa.gov/dashboard/

10. The Charge for the Dashboard Develop a “first-stop-shop” for environmental chemical data to support EPA and partner decision making: Centralized location for relevant chemical data Chemistry, exposure, hazard and dosimetry Combination of existing data and predictive models Publicly accessible, periodically updated, curated Easy access to data improves efficiency and ultimately a ccelerates chemical risk assessment

11. Detailed Chemical Pages

12. Experimental and Predicted Data Physchem and Fate & Transport experimental and predicted data Data can be downloaded as Excel, TSV and CSV files

13. Chemical Hazard Data

14. Hazard Data for Atrazine 3723 rows of human/eco hazard data harvested with 3 clicks

15. Safety Data

16. Sources of Exposure to Chemicals

17. Chemical Lists (not all lists are created equal…)

18. Chemical Lists Chemical lists are focused on regulations, specific research efforts and categories 501 lists and growing TSCA Inventory Clean Water Act Hazardous Substances Consumer Products database Chemicals of Emerging Concern PFAS lists Extractables and Leachables …lists are versioned and updated and new lists added 17

19. Remember those Research Projects?

20. Some Research Projects…

21. Some Research Projects…

22. Some Research Projects…

23. What about Pesticides? 16 out of 501 lists 22

24. EPA OPPIN list of >4000 chemicals 23

25. Harvesting Data en masse How easy is it to harvest data for 4000 pesticides Physicochemical properties Fate and transport Toxicity values Bioactivity data in 100s of in vitro data Exposure data Chemical identifiers Links to regulatory assessments

26. Batch Searching

27. Batch Searching is a big enabler https://pubs.acs.org/doi/10.1021/acs.jcim.0c01273 26

28. Batch Search

29. Batch Search – Excel, CSV, SDF file

30. Batch Search

31. Filter chemicals and send to batch search 30

32. There is so much more… In vitro bioactivity data exposing our ToxCast/Tox21 data Exposure data with functional use information and chemical weight fractions in products Real-time QSAR predictions – draw your chemicals to predict 16 toxicity and physicochemical property endpoints Integration to realtime literature searches using Google Scholar and Pubmed Linking to >40 public domain databases 31

33. So now you know the Dashboard… 32

34. Lots of “proof-of-concept” tools in development PoCs are research software builds to prove approaches before moving into production software environments PoCs are to figure out how to address specific questions Assemble data, develop data model(s), test user interface approaches , work with test user base to garner feedback Since PoCs are internal access data refreshes and application updates can be more Underlying APIs are being used in our research 33

35. PoCs have been rebuilt for production Examples of PoCs integrated into production apps WebTEST predictions on the Dashboard Structure/substructure/similarity search 34

36. How to compare Hazard Data? 35

37. How to compare Hazard Data? NOT Easy to interpret… 36

38. Hazard Profile 37 Hazard Comparison module profiles toxicity across chemicals https://www.epa.gov/chemical-research/cheminformatics

39. Hazard Profile On-click view of underlying data 38

40. Data to Excel in <60s 39

41. Simple Analog “read-across” Suppose a chemical has limited data – perform an analog search to find related chemicals with data 40

42. Simple Analog “read-across” Similarity 41

43. Hazard Comparison Profiling 42

44. Hazard Comparison Profiling

45. Where can our tools be applied Emergency Response utility is obvious… Consider East Palestine 44 https://www.cleveland19.com/2023/02/14/ntsb-announces-preliminary-malfunction-that-caused-east-palestine-train-derailment/ POLYPROPYLENE POLYETHYLENE Residue lube oil VINYL CHLORIDE DIPROPYLENE GLYCOL PROPYLENE GLYCOL DIETHYLENE GLYCOL COMBUSTIBLE LIQ., NOS (ETHYLENE GLYCOL MONOBUTYL ETHER) SEMOLINA COMBUSTIBLE LIQ., NOS (ETHYLHEXYL ACRYLATE) POLYVINYL PETROLEUM LUBEOIL POLYPROPYL GLYCOL ISOBUTYLENE BUTYL ACRYLATES, STABILIZED PETRO OIL, NEC ADDITIVES, FUEL BALLS,CTN,M EDCL SHEET STEEL VEGTABLE, FROZEN BENZENE PARAFFIN WAX FLAKES, POWDER HYDRAULIC CEMENT AUTOS PASSENGER MALT LIQUORS

46. Cheminformatics Safety Module (NOT PUBLIC) Integrate multiple data streams… 45

47. EPA Measurement Data 46 Measurement data are needed to ensure chemical safety Characterize risk Regulate use & disposal Manage human & ecological exposures Ensure compliance under federal statutes Chemical Monitoring Needs Exposure Assessment Dose- Response Assessment Risk Characterization Hazard Identification

48. Applications of Exposomics at EPA Ongoing efforts applying NTA to exposomics challenges including PFAS identification Pesticides in various matrices CECs in water Biosolids Examples include… 47

49. Example 1: Consumer Product Analysis 48

50. Example 2: Recycled Product Analysis 49

51. Example 3: Placental Tissue Analysis 50

52. Applications of Exposomics at EPA Ongoing efforts applying NTA to exposomics challenges including PFAS identification Pesticides in various matrices CECs in water Biosolids Cheminformatics is a key component of NTA analysis Structure standardization (MS-Ready structure forms) Predictive models (LCMS amenability, retention time prediction) in silico mass spectrometry prediction Chemical Space Mapping Chemical Transformation database Analytical Methods and Open Spectral database 51

53. AMOS: Analytical Methods and Open Spectra (NOT PUBLIC yet) Simple Vision: I want to find the best method(s) associated with a chemical and/or class of chemicals Answer the question “I cannot find a method for my chemical” - HELP The Approach: Aggregate MS method documents (and adjust the definition of “what is a useful method”) Extract chemistry (mostly CASRN and Names) Map CASRN and Names to structures Deliver a proof-of-concept application to search a database by names, CASRNs, InChIKeys and ultimately structure 52

54. AMOS: Analytical Methods and Open Spectra (NOT PUBLIC yet) Three types of data in the database: Methods (regulatory, lab manuals and SOPs, publications, tech notes) Spectra (from public domain and our own laboratories) Monographs (harvested from SWGDRUG and other sites) Some methods have associated spectra Some data are just externally linked Currently contains around 673k spectra, 600k external links, >27k “Fact Sheets” and >5600 methods Spectra – LC-MS, GC-MS, NMR ALL data are growing in number with weekly releases 53

55. AMOS database

56. General Search – Mass Spectra 55

57. General Search – Mass Spectrum Metadata 56

58. 345 Pesticide Methods for 2705 substances 57

59. Functional Use Classifications – Directed Graph Visualization 58

60. …to find methods for those chemicals 59

61. Mass Spectral Searching 60

62. Method Search based on chemical similarity 61

63. Batch Search 62 Search a set of DTXSIDs, download info on spectra and methods and links to original data

64. Chemical Classification Search: ClassyFire 63

65. Adding new methods We add methods based on agency needs and feedback Yesterday’s training “What do you have for Milneb”? We search PubMed, Google Scholar, application notes from vendors, government agencies (Domestic and International) 64

66. Added overnight 65

67. How do we do it? 66

68. 9 of 10 chemicals found – no “ Manneb ” 67

69. Chemical Transformation Simulator Database 68

70. ChET : Chemical Transformations Database

71. ChET Reaction Map Lists 70

72. ChET Visual Reaction Maps Compare and overlap maps Load all maps containing a particular chemical Prune and filter maps 71

73. Our cheminformatics work supports the “NTA WebApp” 72

74. Our cheminformatics work supports the “NTA WebApp” 73

75. Full presentation https://t.ly/4MxFe 74

76. The CompTox API is now public https://api-ccte.epa.gov/docs/index.html 75

77. Conclusions Underpinning chemistry data is from the DSSTox database CompTox Chemicals Dashboard is public access to DSSTox and other related databases Proof-of-Concept (PoC) tools are built to prove approaches Everything is increasingly API driven and APIs are now public 76

78. Some Related Publications of Interest

79. You want to know more… Lots of resources available Presentations: https://tinyurl.com/w5hqs55 Communities of Practice Videos: https://rb.gy/qsbno1 Manual: https://rb.gy/4fgydc Latest News: https://comptox.epa.gov/dashboard/news_info 78

80. This talk is an overview This talk is a high-level overview only. We can provide trainings into the individual modules and data as required LOTS of training materials are available https://www.epa.gov/chemical-research/new-approach-methods-nams-training

81. Acknowledgments Our DSSTox curation team SCDCD software development and DevOps teams Scientists and students across CCTE Non-targeted analysis and mass spectrometry team Dashboard project team – Nisha Sipes & Phuc Do Cheminformatics Modules and Modeling Team – Valery Tkachenko, Todd Martin, Nate Charest, Charlie Lowe ChET – Adam Edelman-Munoz, Caroline Stevens and team ChemSTER – Nate Charest and Adam Edelman-Munoz External collaborators and contributors of data 80

82. Contact Information Contact info: [email protected] Slides available at: https://www.slideshare.net/AntonyWilliams/ Obtain articles from Google Scholar Profile 81