Improved prediction of PFAS partitioning with PPLFERs and QSPRs

Abstract

Per- and polyfluoroalkyl substances (PFAS) are chemicals of high concern and are undergoing hazard and risk assessment worldwide. Reliable physicochemical property (PCP) data are fundamental to assessments. However, experimental PCP data for PFAS are limited and property prediction tools such as quantitative structure–property relationships (QSPRs) therefore have poor predictive power for PFAS. New experimental data from Endo 2023 are used to improve QSPRs for predicting poly-parameter linear free energy relationship (PPLFER) descriptors for calculating water solubility (S_W), vapor pressure (VP) and the octanol–water (K_OW), octanol–air (K_OA) and air–water (K_AW) partition ratios. The new experimental data are only for neutral PFAS, and the QSPRs are only applicable to neutral chemicals. A key PPLFER descriptor for PFAS is the molar volume and this work compares different versions and makes recommendations for obtaining the best PCP predictions. The new models are included in the freely available IFSQSAR package (version 1.1.1), and property predictions are compared to those from the previous IFSQSAR (version 1.1.0) and from QSPRs in the US EPA's EPI Suite (version 4.11) and OPERA (version 2.9) models. The results from the new IFSQSAR models show improvements for predicting PFAS PCPs. The root mean squared error (RMSE) for predicting log K_OWversus expected values from quantum chemical calculations was reduced by approximately 1 log unit whereas the RMSE for predicting log K_AW and log K_OA was reduced by 0.2 log units. IFSQSAR v.1.1.1 has an RMSE one or more log units lower than predictions from OPERA and EPI Suite when compared to expected values of log K_OW, log K_AW and log K_OA for PFAS, except for EPI Suite predictions for log K_OW which have a comparable RMSE. Recommendations for future experimental work for PPLFER descriptors for PFAS and future research to improve PCP predictions for PFAS are presented.