Assembly and Curation of Lists of Per- and Polyfluoroalkyl Substances (PFAS) to Support Environmental Science Research

Abstract

Per- and polyfluoroalkyl substances (PFAS) are a class of man-made chemicals of global concern for many health and regulatory agencies due to their widespread use and persistence in the environment (in soil, air, and water), bioaccumulation, and toxicity. This concern has catalyzed a need to aggregate data to support research efforts that can, in turn, inform regulatory and statutory actions. An ongoing challenge regarding PFAS has been the shifting definition of what qualifies a substance to be a member of the PFAS class. There is no single definition for a PFAS, but various attempts have been made to utilize substructural definitions that either encompass broad working scopes or satisfy narrower regulatory guidelines. Depending on the size and specificity of PFAS substructural filters applied to the U.S. Environmental Protection Agency (EPA) DSSTox database, currently exceeding 900,000 unique substances, PFAS substructure-defined space can span hundreds to tens of thousands of compounds. This manuscript reports on the curation of PFAS chemicals and assembly of lists that have been made publicly available to the community via the EPA's CompTox Chemicals Dashboard. Creation of these PFAS lists required the harvesting of data from EPA and online databases, peer-reviewed publications, and regulatory documents. These data have been extracted and manually curated, annotated with structures, and made available to the community in the form of lists defined by structure filters, as well as lists comprising non-structurable PFAS, such as polymers and complex mixtures. These lists, along with their associated linkages to predicted and measured data, are fueling PFAS research efforts within the EPA and are serving as a valuable resource to the international scientific community.

Keywords: cheminformatics; computational toxicology; environmental chemistry; pfas (perfluorinated alkylated substances); web-based information.

FIGURE 1 |

The collection of substructures used to define the PFASSTRUCTv3 list. Atoms replacing hydrogen (denoted by the red “A”) are all potential sites of substitution. The trifluoromethanesulfonic acid substructure (contained in the box) was included in PFASSTRUCTv3 but excluded in the subsequent PFASSTRUCTv4 iteration.

FIGURE 2 |

The list of non-explicit PFAS structures includes both Class 1 Markush structure representations as well as Class 2 which have no associated structures, but which may be mapped to related substances such as monomer units as exemplified by polytetrafluoroethylene.

FIGURE 3 |

Example of structures that differ by being fully aliphatic or only partially aliphatic with an aromatic substituent.

FIGURE 4 |

Example of a fully fluorinated and aromatic structure that does not meet any PFAS definition.

FIGURE 5 |

Examples of highly branched structures that do not fit the EPA TSCA 2021 PFAS substructure definition.

FIGURE 6 |

Example of a PFAS ether that does not fit the EPA TSCA 2021 PFAS substructure definition.

FIGURE 7 |

Examples of halogenated chains that do not fit any PFAS structure definition.

FIGURE 8 |

Examples of highly fluorinated chains that do not fit the EPA TSCA 2021 PFAS substructure definition.

FIGURE 9 |

Examples of alkenic fluorinated chain and ring systems that do not fit the EPA TSCA 2021 PFAS substructure definition. The first two do not fit any PFAS structural definition.

FIGURE 10 |

Examples of large molecules with a very small fluorinated moiety that fits the OECD-PFAS 2021 definition but not more restricted definitions.