Solvent Suitability for HFPO-DA (“GenX” Parent Acid) in Toxicological Studies

Per- and polyfluorinated alkyl substances (PFAS) are of significant interest because of their prevalence and environmental persistence. In addition, for many PFAS, including fluorinated ethers such as hexafluoropropylene oxide dimer acid (HFPO-DA, or the parent acid of "GenX"), toxicological data are sparse. In general, in vitro testing frequently uses dimethyl sulfoxide (DMSO) as a carrier solvent due to its low toxicity, solubility across vast chemical space, and permeation across biological barriers. For PFAS, laboratory practice has assumed that the materials are stable across a wide range of solvents, pHs, and temperatures. In this study, HFPO-DA stability was evaluated with DMSO and other commonly used solvents to determine each solvent's suitability for use in toxicity assays. The formation of HFPO-DA's degradation product, heptafluoropropyl 1,2,2,2-tetrafluoroethyl ether (Fluoroether E-1), was monitored by headspace gas chromatography–mass spectrometry over time. These experiments revealed degradation of HFPO-DA to Fluoroether E-1 in DMSO and other aprotic, polar solvents, with half-lives on the order of hours (1, 1.25, and 5.2 h for DMSO, acetone, and acetonitrile, respectively). This rapid degradation suggests the need for caution when performing or using data from toxicity assessments on HFPO-DA and closely related PFAS.