Nontarget Identification of Novel Per- and Polyfluoroalkyl Substances in Cord Blood Samples

Abstract

Per- and polyfluoroalkyl substances (PFASs) can penetrate the placental barrier and reach embryos through cord blood, probably causing adverse birth outcomes. Therefore, novel PFASs identification in cord blood and their relationships with birth outcomes are essential to evaluate prenatal exposure risk of PFASs. Herein, 16 legacy and 12 novel PFASs were identified in 326 cord blood samples collected from pregnant women in Jinan, Shandong, China. The presence of perfluoropolyether carboxylic acids, hydrogen-substituted polyfluoroetherpropane sulfate, and 3:3 chlorinated polyfluoroalkyl ether alcohol in cord blood was reported for the first time. Two extensive OECD (Organization for Economic Co-operation and Development)-defined PFASs named fipronil sulfone and 2-chloro-6-(trifluoromethyl)pyridine-3-ol were also identified. Quantification results showed that the emerging and OECD-defined PFASs separately accounted for 9.4 and 9.7% of the total quantified PFASs, while the legacy PFOA, PFOS, and PFHxS were still the most abundant PFASs with median concentrations of 2.12, 0.58, and 0.37 ng/mL, respectively. Several PFASs (C9-C12 PFCAs, C6-C8 PFSAs, and 6:2 Cl-PFESA) showed significantly higher levels for older maternities than younger ones. PFHxS levels were positively associated with birth weight and ponderal index (p < 0.05). The results provide comprehensive information on the presence and exposure risks of several novel PFASs during the early life stage.

Suspect, Nontarget Screening, and Toxicity Prediction of Per- and Polyfluoroalkyl Substances in the Landfill Leachate

“…Cl-PFPECAs presented a 3:1 isotope distribution of the isotope peaks [M] − and [M + 2] − , and thus its molecule contains a chlorine atom. The molecular ions of Cl-PFPECAs were prone to be dissociated to their precursor ion [M – CF 2 CO 2 ] − during ionization, and both of them can be observed (e.g., ClPFPECA-0,3, m / z 792.8968 to 698.9100) as reported, and in most cases the molecular ions of Cl-PFPECAs cannot be observed, and thus they may be identified as chlorinated perfluoropolyether alcohols (Cl-PFPEOHs). , However, Cl-PFPEOHs should be difficult to ionized into their [M – H] − adduct owing to their relative higher p K a values > 4 on hydroxyl group than those (p K a from −3 to 2) of carboxyl and sulfonic acid groups of most legacy and emerging PFASs. Except for the fragment ions of [CF 3 ] − ( m / z 68.9958), [C 2 F 5 ] − ( m / z 118.9925) and [C 3 F 7 O] − ( m / z 184.9842), chlorine-containing fragments including [C 2 ClF 4 ] − ( m / z 134.9630), [C 3 ClF 6 O] − ( m / z 200.9547), [C 5 ClF 10 O 2 ] − ( m / z 316.9432), [C 6 ClF 12 O 2 ] − ( m / z 366.9400), [C 7 ClF 14 O 3 ] − ( m / z 432.9317), [C 8 ClF 16 O 3 ] − ( m / z 482.9285), [C 9 ClF 18 O 3 ] − ( m / z 532.9254), [C 9 ClF 18 O 4 ] − ( m / z 548.9203), and [C 10 ClF 20 O 4 ] − ( m / z 598.9171) were found in MS 2 spectra of Cl-PFPECAs, where neutral losses of C 3 F 6 O, C 5 F 10 O 2 , C 6 F 12 O 2 , C 8 F 16 O 3 , or C 10 F 20 O 4 were observed with the cleavage of their ether bonds (Figures S11–S18).…”

“…Therefore, the molecular docking approach was preferred over the ML-based approach when the 3D structure of the protein was clear. Then, two molecular docking models on PPARα and ERα receptors were then applied for predicting the toxicity of the 48 identified PFASs and to study the interaction mechanism between PFASs and target receptors, , especially for those chemicals without experimental data.…”

“…Recently, emerging PFASs were identified in human, wild animals, and various environmental samples, ,, but the studies of their potential toxicity and health risk were limited owing to the few commercial standards available for traditional in vivo or in vitro testing experiments. In 2018, EPA initialized a program that aims to prioritize the data-poor PFAS for risk assessment through characterizing their activities against 150 representative PFASs including 142 distinct parent structures. , PFASs were tested using two multiplexed transcription factor (TF) activation bioassays that covered a total of 81 TF end points and specificity controls.…”

Critical Assessment of the Chemical Space Covered by LC–HRMS Non-Targeted Analysis

“…There were 11 publications where the analysis was reported in both modes, but the details were insufficient for determining whether the experiment was performed simultaneously or separately in both modes. In three other studies, an exclusively negative mode was used to prioritize a specific group of compounds of interest, such as PFAS, − deliberately narrowing down the investigated chemical space. Finally, two of the reviewed studies employed simultaneous positive and negative ionization modes with formic acid as a modifier.…”

Efficient PFAS prioritization in non-target HRMS data: systematic evaluation of the novel MD/C-m/C approach

“…1. Abbreviations: SF 5 -PFOS, pentafluorosulfanyl perfluorooctane sulfonic acid [29]; F53-b, 6:2 Cl-perfluoro ether sulfonic acid; PFO6TeDA, perfluoro-(3,5,7,9,11,13-hexaoxatetradecanoic) acid [30]; PFOS, perfluorooctane sulfonic acid; C6O4, perfluoro ([5-methoxy-1,3-dioxolan-4-yl]oxy) acetic acid; GenX or HFPO-DA, hexafluoropropylene oxide dimer acid; ADONA, dodecafluoro-3H-4,8-dioxanonanoate; PFOA, perfluorooctanoic acid; 6:2 diPAP, 6:2 polyfluoroalkyl phosphate diester; 6:2 FTOH, 6:2 fluorotelomer alcohol; AmPr-FHxSA, N-dimethyl ammonio propyl perfluorohexane sulfonamide [31]; Capstone B (also 6:2 FTAB), 6:2 fluorotelomer sulfonamide alkylbetaine [32]. For the predicted F/C, the table provided as Electronic Supplementary Material was used.…”