Informatics Approaches supporting UVCB Chemicals in the US-EPA CompTox Chemicals Dashboard

Informatics Approaches supporting UVCB Chemicals in the US-EPA CompTox Chemicals Dashboard

1. 1. Informatics Approaches supporting UVCB Chemicals in the US-EPA CompTox Chemicals Dashboard Antony Williams1, Chris Grulke1 and Emma Schymanski2 Center for Computational Toxicology and Exposure, U.S. Environmental Protection Agency, RTP, NC Luxembourg Center for Systems Biomedicine, University of Luxembourg, Luxembourg, Europe November 2019 SETAC, Toronto, Canada http://www.orcid.org/0000-0002-2668-4821 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
2. 2. Overview • The CompTox Chemicals Dashboard - web- based database of 875k substances • Associated data including: – Experimental and predicted physicochemical data – In vivo hazard data – In vitro bioactivity screening data – Link farm to tens of public resources • Integrated modules – read-across, lit search • Data mappings and searches supporting Mass Spectrometry & structure identification 1
3. 3. CompTox Chemicals Dashboard https://comptox.epa.gov/dashboard 2 875k Chemical Substances
4. 4. BASIC Search 3
5. 5. Detailed Chemical Pages 4
6. 6. Human and Eco Hazard Data • ToxVal Database contains following data: –~700,000 toxicity values –~30 sources of data –~22,000 sub-sources –~5000 journals cited –~70,000 literature citations 5
7. 7. In Vitro Bioassay Screening ToxCast and Tox21 6
8. 8. Related Substances – Transformation Products, “Monomer-Polymer” 7 What No Structures???
9. 9. “UVCB” Chemical Substances 8
10. 10. UVCB Chemicals 9
11. 11. Lots of UVCBS in Commerce…. 10
12. 12. Example UVCBs with no structures 11 • Aroclor 1254 • Toxaphene • Xylenes • Demeton • Aroclor 1248 • Asbestos • Technical chlordane • Coke oven emissions • Creosote • Diesel engine exhaust • Nickel refinery dust • Nickel, soluble salts • Refractory ceramic fibers • Toluene diisocyanate
13. 13. What is Toxaphene? “Complex, but reproducible mixture of at least 175 distinct C10-chloro compounds, having an approximate overall empirical formula of C10H10Cl8.; the 2 most active components are a C10H10Cl8 compound and a C10H11Cl7 compound which had been elucidated as 2,2,5-endo,6-exo,8,9,10-heptachlorobornane. Produced by the chlorination of camphene to 67-69% chlorine by weight and made up of compds. of C10 H8 Cl10, C10 H18-n Cl n (mostly poychloroboranes) and C10 H16-n Cl n (oychloroboranes and/or polychlorotricyclenes) with n = 6 to 9” 12
14. 14. Toxaphene has rich data 13
15. 15. UVCB: Mapped Chemicals Polymer individual components
16. 16. Linear Alkylbenzenesulfonates 15 • Ambiguous representations of some structures are possible • “Markush” representations can be valuable for describing and mapping chemicals
17. 17. “Markush Structures” https://en.wikipedia.org/wiki/Markush_structure 16
18. 18. Chemical “grouping” – PCBs, PBDEs 17 PCBs PBDEs
19. 19. Some Markush chemicals are bounded 18 Previously 1-1 mapping
20. 20. Now Markush Enumeration 19
21. 21. UVCB: Complex Surfactants 20
22. 22. UVCB: Complex Surfactants 21
23. 23. Chemical Lists and Categories 22
24. 24. EPAHFR: Hydraulic Fracturing 23
25. 25. TSCA Inventory 24
26. 26. TSCA Inventory List Active Non-confidential portion 25 Over 11,500 out of 23,500 have NO STRUCTURES
27. 27. Batch Searching 26
28. 28. Batch Searching • Singleton searches are useful but people generally want data on LOTS of chemicals! • Typical questions – What is the list of chemicals for the formula CxHyOz – What is the list of chemicals for a mass +/- error – Can I get chemical lists in Excel files? In SDF files? – Can I include properties in the download file? 27
29. 29. Batch Search Names 28 Excel Download
30. 30. Add Other Data of Interest 29
31. 31. Related Substance Relationships
32. 32. Conclusion • Building an integrated hub for environmental chemistry data to serve computational toxicology • Transparent access to data and models – file downloads, SQL data dumps and web services • Expansion of functionality to serve all data streams generated by NCCT across the agency & community 31 • Data QUALITY is a key focus - ongoing curation • Ongoing API development will provide enhanced access to data streams
33. 33. Acknowledgements EPA-RTP • An enormous team of contributors from CCTE, especially the IT software development team • Our curation team for their care and focus on data quality • Multiple centers and laboratories across the EPA • Many public domain databases and open data contributors
34. 34. Contact Antony Williams CCTE, US EPA Office of Research and Development, Williams.Antony@epa.gov ORCID: https://orcid.org/0000-0002-2668-4821 33 https://doi.org/10.1186/s13321-017-0247-6