Extractable organofluorine (EOF) and target PFAS, including trifluoroacetic acid (TFA), in human serum from a Norwegian cohort, with a case study on the impact of fluorinated pharmaceuticals

This study investigated the amount and proportion of unidentified organofluorine (UOF) in human serum and assessed short-term variability in exposure using extractable organofluorine (EOF) analysis and a fluorine mass balance approach. Serum samples were obtained from the well-characterized EuroMix cohort, comprising residents living in and around Oslo, Norway, collected between September 2016 and November 2017. Short-term intra-individual variability was evaluated using 72 paired serum samples collected 2-3 weeks apart. An extended target list of 64 PFAS, including trifluoroacetic acid (TFA), was applied to quantify identified and unidentified EOF. UOF accounted for up to 81% of EOF (median: 38%) in EuroMix samples. In 36% of paired samples, EOF concentrations varied by more than 25% over the 2-3-week interval, indicating the presence of compounds with relatively short biological half-lives. TFA was the most abundant individual PFAS detected, with median concentrations approximately twice those of PFOS. In a separate case study, serum samples from individuals using the fluorinated pharmaceutical Fluoxetine showed substantially elevated EOF and TFA concentrations (EOF: median 140 ng F/mL; TFA: median 27.7 ng/mL) compared with samples from individuals not using Fluoxetine (EOF: median < 8 ng F/mL; TFA: median 6.22 ng/mL). These findings indicate that fluorinated pharmaceuticals may contribute significantly to circulating EOF and TFA in humans. The large fraction of UOF and the widespread occurrence of TFA highlight the need to identify their sources relevant to human exposure. Together, these findings indicate that current PFAS including TFA biomonitoring approaches capture only a fraction (estimated to be 50%) of total human exposure to fluorinated substances and highlight the need to complement target analysis with fluorine mass balance approaches in future exposure assessment.