Per- and Polyfluoroalkyl Substances (PFAS) in PubChem: 7 Million and Growing

Abstract

Per- and polyfluoroalkyl substances (PFAS) are of high concern, with calls to regulate them as a class. In 2021, the Organisation for Economic Co-operation and Development (OECD) revised the definition of PFAS to include any chemical containing at least one saturated CF₂ or CF₃ moiety. The consequence is that one of the largest open chemical collections, PubChem, with 116 million compounds, now contains over 7 million PFAS under this revised definition. These numbers are several orders of magnitude higher than previously established PFAS lists (typically thousands of entries) and pose an incredible challenge to researchers and computational workflows alike. This article describes a dynamic, openly accessible effort to navigate and explore the >7 million PFAS and >21 million fluorinated compounds (September 2023) in PubChem by establishing the "PFAS and Fluorinated Compounds in PubChem" Classification Browser (or "PubChem PFAS Tree"). A total of 36500 nodes support browsing of the content according to several categories, including classification, structural properties, regulatory status, or presence in existing PFAS suspect lists. Additional annotation and associated data can be used to create subsets (and thus manageable suspect lists or databases) of interest for a wide range of environmental, regulatory, exposomics, and other applications.

Keywords: chemical database; chemical regulation; classification; exposure; high-resolution mass spectrometry; identification; open science; per- and polyfluoroalkyl substances.

Figure 1

PFAS and Fluorinated Compounds in PubChem collection showing the six top nodes and the first layer of subnodes; collection available at https://pubchem.ncbi.nlm.nih.gov/classification/#hid=120. Image created September 16, 2023.

Figure 2

PFAS content according to the 2021 OECD definition (A) excluding salts and mixtures; (B) including salts and mixtures; (C) subnodes of the “Breakdown by PFAS functional groups” for PFAS-S; (D) Adding the keyword “PFAS-S(=O)2-N” to the search bar in the Classification Browser allows users to quickly find sulfonamide and related PFAS. Image created September 16, 2023.

Figure 3

Exploring the contents of fluorine-containing pesticides, S94 FLUOROPEST,^, with the PubChem PFAS Tree: (A) OECD PFAS (195) and organofluorine content (313 of 318 entries—the missing entries are salts); (B) breakdown of PFAS (with salts), also showing heteroatom connections; (C) breakdown by connectivity degree and PFAS part formulas, revealing that most pesticides contain CF₂ or CF₃. Image created June 17, 2023, using PubChem Entrez functionality, explained further in the documentation.

Figure 4

Regulatory collection: example of PFHxS with two different definitions (Annex A of the Stockholm Convention and a draft definition for EU REACH) from September 16, 2023. The main image shows how the node and EU REACH subnode are constructed; the inset shows the breakdown by annotation content to help find the most relevant (or recent) matches (also available for Annex A).

Figure 5

Interacting with annotation information associated with the PFAS content in PubChem. (A) The “saved searches” panel, which allows exploration of the overlap (AND, OR, NOT) between various categories and searches via the blue panel at the top (query names can be edited). (B) Any search, or combination of searches, can be downloaded in a variety of formats (download fields described in the text). (C) Chemical stripes⁻ on the patent data for PFOS, extracted from the PubChem patent tables. (D) Chemical stripes for PFOS based on consolidated reference values, extracted from PubChem Consolidated References tables.