Fluorine Mass Balance, including Total Fluorine, Extractable Organic Fluorine, Oxidizable Precursors, and Target Per- and Polyfluoroalkyl Substances, in Pooled Human Serum from the Tromsø Population in 1986, 2007, and 2015.

Of the thousands of per- and polyfluoroalkyl substances (PFAS) known to exist, only a small fraction (≤1%) are commonly monitored in humans. This discrepancy has led to concerns that human exposure may be underestimated. Here, we address this problem by applying a comprehensive fluorine mass balance (FMB) approach, including total fluorine (TF), extractable organic fluorine (EOF), total oxidizable precursors (TOP), and selected target PFAS, to human serum samples collected over a period of 28 years (1986, 2007, and 2015) in Tromsø, Norway. While concentrations of TF did not change between sampling years, EOF was significantly higher in 1986 compared to 2007 and 2015. The ∑12PFAS concentrations were highest in 2007 compared to 1986 and 2015, and unidentified EOF (UEOF) decreased from 1986 (46%) to 2007 (10%) and then increased in 2015 (37%). While TF and EOF were not influenced by sex, women had higher UEOF compared to men, opposite to target PFAS. This is the first FMB in human serum to include TOP, and it suggests that precursors with >4 perfluorinated carbon atoms make a minor contribution to EOF (0-4%). Additional tools are therefore needed to identify substances contributing to the UEOF in human serum.

Legacy perfluoroalkyl acids and their oxidizable precursors in plasma samples of Norwegian women.

Humans are exposed to perfluoroalkyl acids (PFAA) mainly through direct pathways, such as diet and drinking water, but indirect exposure also occurs when PFAA precursors break down to form legacy PFAA. Exposure to PFAA precursors raises particular concern, as neither the exposure nor the precursors themselves have been well described. In the present study, we aimed to assess the indirect contribution of oxidizable PFAA precursors to the total per- and polyfluoroalkyl substances (PFAS) burden in human plasma following the voluntary phase-out of production of long-chain PFAS. In addition, multiple logistic regression was used to explore associations between selected lifestyle and dietary factors and the oxidizable PFAA precursors fraction. This study included 302 cancer-free participants of the Norwegian Women and Cancer postgenome cohort. PFAS analyses were performed in plasma samples to determine PFAS concentrations before and after oxidation with the Total Oxidizable Precursor (TOP) assay. In pre-TOP analyses, perfluorooctane sulfonic acid (PFOS) was the dominant compound, followed by perfluorooctanoic acid (PFOA).The vast majority (98%) of the study population had increased post-TOP concentrations for at least one PFAA. The formation of PFAA accounted for 12% of the total PFAS burden, with seven PFAA observed post-TOP in at least 30% of study participants. PFHpA, br- PFOA, and PFDA were only detected in post-TOP analyses and showed the highest increase in concentrations. Of the PFAA with increased concentrations, we noted significant associations for year of birth, parity, BMI, and some dietary factors, although they were not consistent between the different PFAA. These results indicate that while the TOP assay might not provide a complete assessment of total PFAS burden in humans, it offers comprehensive assessment of unknown PFAA precursors that might be present in plasma, and it could therefore be implemented as an auxiliary tool in this regard.

Total oxidizable precursors assay for PFAS in human serum.

Per- and polyfluoroalkyl substances (PFAS) are a class of chemicals including over 4700 substances. As a limited number of PFAS is routinely analyzed in human serum, complementary analytical methods are required to characterize the overlooked fraction. A promising tool is the total oxidizable precursors (TOP) assay to look for precursors by oxidation to perfluoroalkyl acids (PFAA). The TOP assay was originally developed for large volumes of water and had to be adapted for 250 µL of human serum. Optimization of the method was performed on serum samples spiked with model precursors. Oxidative conditions similar to previous TOP assay methods were not sufficient for complete oxidation of model precursors. Prolonged heating time (24 h) and higher oxidant amount (95 mg of Na2S2O8 per 225 µL of serum) were needed for complete conversion of the model precursors and accomplishing PFAA yields of 35-100 %. As some precursors are not fully converted to PFAA, the TOP assay can only provide semi-quantitative estimates of oxidizable precursors in human serum. However, the TOP assay can be used to give indications about the identity of unknown precursors by evaluating the oxidation products, including perfluoroalkyl sulfonic acids (PFSA) and perfluoroalkyl ether carboxylic acids (PFECA). The optimized TOP assay for human serum opens the possibility for high-throughput screening of human serum for undetected PFAA precursors.

Optimization of a low flow sampler for improved assessment of gas and particle bound exposure to chlorinated paraffins.

An optimized low volume sampler was developed to determine both gas- and particle bound concentrations of short and medium-chain chlorinated paraffins (S/MCCPs). Background contamination was limited by the sampler design, providing method quantification limits (MQLs) at least two orders of magnitude lower than other studies within the gas (MQL: 500 pg (ΣSCCPs), 1.86 ng (ΣMCCPs)) and particle (MQL: 500 pg (ΣSCCPs), 1.72 ng (ΣMCCPs) phases. Good repeatability was observed between parallel indoor measurements (RSD ≤ 9.3% (gas), RSD ≤ 14% (particle)) with no breakthrough/saturation observed after a week of continuous sampling. For indoor air sampling, SCCPs were dominant within the gas phase (17 ± 4.9 ng/m3) compared to MCCPs (2.7 ± 0.8 ng/m3) while the opposite was observed in the particle bound fraction (0.28 ± 0.11 ng/m3 (ΣSCCPs) vs. 2.7 ± 1.0 ng/m3 (ΣMCCPs)). Only SCCPs in the gas phase could be detected reliably during outdoor sampling and were considerably lower compared to indoor concentrations (0.27 ± 0.10 ng/m3). Separation of the gas and particle bound phase was found to be crucial in applying the appropriate response factors for quantification based on the deconvoluted S/MCCP sample profile, thus avoiding over- (gas phase) or underestimation (particle phase) of reported concentrations. Very short chain chlorinated paraffins (vSCCPs, C5-C9) were also detected at equal or higher abundance compared to SCCP congener groups (C10-C13) congener groups, indicating an additional human indoor inhalation risk.