Bioaccumulation of Novel Per- and Polyfluoroalkyl Substances in Mice Dosed with an Aqueous Film-Forming Foam

Abstract

Per-and polyfluoroalkyl substances (PFASs) are widespread in the blood of the general human population, and their bioaccumulation is of considerable scientific and regulatory interest. PFAS exposure resulting from aqueous film-forming foam (AFFF) ingestion is poorly understood due to the complexity of AFFF mixtures and the presence of polyfluorinated substances that may undergo metabolic transformation. C57BL/6 mice were dosed with an AFFF primarily containing electrochemically fluorinated PFASs for 10 days, followed by a 6 day depuration. Urine was collected throughout the study and serum was collected postdepuration. Samples were analyzed via high-resolution mass spectrometry. Relative to the dosing solution, C6 and C7 perfluoroalkyl sulfonates (PFSAs) were enriched in dosed mouse serum, suggesting in vivo transformation of sulfonamide precursors. Some substituted C8 PFSAs [keto-perfluorooctane sulfonate (PFOS), hydrogen-PFOS, and unsaturated PFOS] appeared to be more bioaccumulative than linear PFOS, or were formed in vivo from unidentified precursors. A series of seven peaks in dosed mouse serum was tentatively identified as sulfonimide dimers that were either a minor component of the AFFF or were formed via metabolism of other AFFF components. This work highlights the importance of sulfonamide precursors in contributing to bioaccumulation of AFFF-associated PFSAs and identifies several classes of potentially bioaccumulative novel PFASs that warrant further investigation.

In-Vitro and In-Silico Assessment of Per- and Polyfluoroalkyl Substances (PFAS) in Aqueous Film-Forming Foam (AFFF) Binding to Human Serum Albumin

“…Most PFAS identified in this study were also reported by Houtz et al (2013) [ 49 ], Barzen-Hanson et al (2017) [ 2 ], and McDonough et al (2020) [ 29 ] for the same or similar AFFF commercial products. We qualified C 4 and C 6 perfluoroalkyl sulfonamide amino carboxylates and perfluoroalkyl sulfonamido amines that were reported by Houtz et al One pentafluorosulfide-containing eight perfluorocarbon PFAS (8-F5S-PFOS) found in AFFF was also reported by Barzen-Hanson et al We qualified four of six PFOS-substituted compounds (H-PFOS, U-PFOS, Cl-PFOS, and K-PFOS) and one of two PFDS-substituted compounds (H-PFDS) reported by McDonough et al A C 6 containing phosphonic acid and ester functional groups (8:2 monoPAP-diEes) identified in this study was detected in PFAS-contaminated soil (from paper sludge) in Germany [ 50 ].…”

“…We calculated pseudo-bioconcentration factors (BCF pseudos ) for noncovalently bound and potentially covalently bound fractions separately to evaluate patterns related to perfluorocarbon chain length and functional groups ( Figure 5 ). BCF pseudo serves as a quantitative benchmarking technique to cross-compare bioaccumulation potentials of novel PFAS using qualitative screening data [ 29 ]. The BCF pseudo was calculated for each PFAS as follows: where A i ,sample is the peak area of compound i detected in the protein aliquot or pellet; A L-PFOS,sample is the peak area of L-PFOS detected in the protein aliquot or pellet; A L-PFOS,AFFF is the peak area of L-PFOS detected in neat AFFF dilutions; and A i ,AFFF is the peak area of compound i detected in neat AFFF dilutions.…”

“…To assess the ability of in-vitro binding studies with HSA to represent bioaccumulation potentials of PFAS in animals, we compared our BCF pseudos from the noncovalently bound fraction to pseudo-bioaccumulation factors (BAF pseudos ) calculated in an in-vivo mouse-dosing study that used the same AFFF commercial product [ 29 ]. Our calculation of BCF pseudo .…”

“…For analogs of well-known PFSAs identified, we added common contractions to enhance recognizability. For instance, PFOS analogs include chloro (Cl), ketone (K), unsaturated (U), hydrogen (H), linear (L), and branched (br)-substituted PFOS [ 29 ].…”

Invited Perspective: PFAS Bioconcentration and Biotransformation in Early Life Stage Zebrafish and Its Implications for Human Health Protection

“…Exposure to the perfluorooctanesulfonamido ammonium (PFOSAmS), for example, resulted in the detection of 74 biotransformation products (Han et al 2021). This number is in line with the 92 parent and biotransformation products detected in mice exposed to PFAS-containing aqueous film-forming foam (AFFF) (McDonough et al 2020). Accordingly, human PFAS risk assessment strategies likely need to consider internal PFAS mixtures from direct accumulation and, as an additional source, biotransformation.…”