Data delivery from the US-EPA Center for Computational Toxicology and Exposure to support food toxin researchers

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 have served the chemistry community for many years. Several web-based software applications have been developed at the US-EPA and made available to the community to provide access to information regarding mycotoxins. This includes related structures, experimental and predicted properties, hazard data and mass spectrometry analytical data and methods. While the primary software application from the Center is the CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard) almost a dozen proof-of-concept applications have been built serving various capabilities. The publicly accessible Cheminformatics Modules (https://www.epa.gov/chemical-research/cheminformatics) provides access to modules to allow for hazard comparison for sets of chemicals, structure-substructure-similarity searching and batch QSAR prediction of both physicochemical and toxicity endpoints. This presentation will provide an overview of all tools in development that provide access to food toxin related data and the integrated nature of the applications based on the underlying chemistry data set. This will include access to curated chemistry data for food-related toxins, including those generated in storage, analytical chemistry methods for determining the presence of such toxins (harvested from multiple bodies including the Food and Drug Administration), and approaches to harvesting the data en masse for research use and integration into third party informatics systems. This abstract does not necessarily represent the views or policies of the U.S. Environmental Protection Agency.

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 Data delivery from the US-EPA Center for Computational Toxicology and Exposure to support food toxin researchers Antony Williams 1 , Greg Janesch 2 , Tyler Carr 2 and Valery Tkachenko 3 Center for Computational Toxicology and Exposure, US-EPA, RTP, NC ORAU Student Services Contractor ScienceDataExperts Inc. March 2024: Spring Fall Meeting, New Orleans, LA

2. Free-Access Cheminformatics Tools The Center for Computational Toxicology and Exposure has delivered many tools including CompTox Chemicals Dashboard Proof-of-Concept cheminformatics modules Chemicals Hazard Profiling Chemical Transformations Database Analytical Methods and Spectra Chemical Safety Profiling 1

3. Curating Chemistry into the DSSTox Database 2 Chemistry underpins all of our tools Data assembly and curation is critical DSSTox assembled over 25 years

4. 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

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

6. Detailed Chemical Pages

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

8. Chemical Hazard Data

9. Hazard Data for Aflatoxin B1 Human/eco hazard data harvested with three clicks

10. Substance Categories and Mappings 9

11. Substance Categories and Mappings 10

12. Integrated Modules – Abstract Sifter https://comptox.epa.gov/dashboard/chemical/pubmed-abstract-sifter/

13. Integrated Modules – Abstract Sifter 12

14. Chemical Lists

15. Chemical Lists Chemical lists are focused on regulations, specific research efforts and categories >500 lists and growing TSCA Inventory Clean Water Act Hazardous Substances Chemicals of Emerging Concern Food Mycotoxins …lists are versioned and updated and new lists added 14

16. Some Example Lists…

17. Some Research Projects…

18. Harvesting Data en masse Harvesting data for Food Toxins Physicochemical properties Fate and transport Toxicity values Bioactivity data in 100s of in vitro data Exposure data Chemical identifiers Links to regulatory assessments

19. Batch Searching is a big enabler https://pubs.acs.org/doi/10.1021/acs.jcim.0c01273 18

20. Batch Search

21. Batch Search – Excel, CSV, SDF file

22. Batch Search

23. How to compare Hazard Data? NOT Easy to interpret… 22

24. Hazard Profile 23 Hazard Comparison module profiles toxicity across chemicals https://www.epa.gov/chemical-research/cheminformatics

25. Hazard Profile On-Hover view of trumping scheme call 24

26. Hazard Profile On-click view of underlying data 25

27. Data to Excel in <60s 26

28. EPA Measurement Data 27 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

29. When Methods are Not Enough EPA is highly active in the field of non-targeted analysis We have been applying lots of cheminformatics approaches 28

30. Our latest Analytical Project: AMOS 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 29

31. Synonyms, Abbreviations and Chemicals 30 CAS Numbers, Names and Abbreviations can limit what’s possible…

32. Might this be a better view? 31

33. When articles are not closed access…. 32

34. Introducing AMOS Analytical Methods and Spectra Database 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 >630,000 spectra, 600,000 external links, 38,000 “Fact Sheets” and ~5700 methods Spectra – LC-MS, GC-MS, NMR and IR about to be added ALL data are growing in number 33

35. Where are there methods? Agency-based methods EPA, USGS, USDA, CDC, FDA, OSHA, DEA, ATSDR, NIOSH … ASTM and ISO methods Vendor application notes – Bruker, Waters, Agilent, Sciex, Shimadzu, LECO, Thermo Peer-reviewed articles Laboratory Documents – lab manuals, SOPs 34

36. A view of the methods list 35

37. Embedding New Method PDFs 36

38. When Methods are OPEN Access 37

39. When Methods are PubMed OPEN Access 38

40. Proprietary Methods for INTERNAL Access 39

41. Fact Sheets – 38000 of them and growing 40

42. Building a spectrum library to search against 41

43. Linking to actual spectra 42

44. Linking to actual spectra 43

45. 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 44

46. Conclusions Food Toxins are a class of chemicals of interest to EPA The CompTox Chemicals Dashboard is public access to DSSTox and related data containing many mycotoxins A number of other proof-of-concept tools are available publicly and in development Structure/Substructure/Similarity searching (for 1.2 million chemicals) Hazard Comparison Dashboard AMOS: Analytical Method and Open Spectra database 45

47. Contact Information Contact info: [email protected] Slides available at: https://www.slideshare.net/AntonyWilliams/ Obtain articles from Google Scholar Profile 46