Evaluating Legacy and Emerging PFAS in Human Blood Collected from 2003 to 2021

Per- and polyfluoroalkyl substances (PFASs) are a class of manmade chemicals linked to numerous health outcomes including cancers and increased cholesterol. Consequently, legacy PFASs such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) have been voluntarily phased out of production within the United States since the early 2000s. However, as replacements, emerging PFASs have been introduced over the last 25 years. The presence and accumulation of these emerging PFASs remains largely unexplored due to the complexity of their identification and quantification. Here, we analyzed a unique set of serum samples (<i>n</i> = 156) collected from 2003 to 2021 consisting of three groups: an autoimmune proband, a healthy sibling, and an unrelated control. Quantitative analyses revealed no discernible link between PFAS exposure and autoimmune disease diagnosis; however, nontargeted analysis revealed concerning temporal trends in emerging replacement PFASs the significance of which is unknown. We detected a concerning increase in the chlorinated PFOS-replacement 9Cl-PF3ONS and polyfluoroalkyl phosphate species including 6:2 DiPAP and perfluoroalkyl phosphinic acids (PFPis) in human serum across the US since 2003. In addition, we documented the presence of a novel PFAS chloroperfluorononylphosphonic acid (Cl-PFNPA) in human serum. These analyses provide an assessment of how PFAS exposure has changed since 2003 while exploring potential linkages to autoimmune diseases.