Penetration of PFASs Across the Blood Cerebrospinal Fluid Barrier and Its Determinants in Humans

Laboratory studies indicate that exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) can induce neuro-behavioral effects in animals. However, the penetration of PFASs across the brain barrier and its determining factors are yet to be clarified in humans. We studied PFAS levels in 223 matched-pair serum and cerebrospinal fluid (CSF) samples from hospital in-patients using UPLC/MS/MS. Among the 21 target analytes, PFOA, PFOS, and 6:2 Cl-PFESA were dominant in serum, with mean concentrations of 7.4, 6.8, and 6.2 ng/mL, respectively, contributing 79% to the total PFAS burden in serum. In CSF, PFOA, PFOS, and 6:2 Cl-PFESA were again the dominant PFASs, with mean concentrations of 0.078, 0.028, and 0.051 ng/mL contributing 36%, 13%, and 24%, respectively, to the total PFAS burden in CSF. Furthermore, PFAS penetration (R-PFAS, PFAS(CSF)/PFAS(serum)) was positively correlated with the barrier permeability index R-Alb (Albumin(CSF)/Albumin(serum)), indicating that barrier integrity was the main determinant of PFAS penetration across the blood-CSF barrier. Positive associations between the R-PFAS values of the main PFASs and serum C-reactive protein were observed, implying that inflammation facilitates the penetration of PFASs across the brain barrier.