Number of Carbons Is a Critical Parameter for Accumulation of Per- and Polyfluoroalkyl Substances in the Human Brain

Per- and polyfluoroalkyl substances (PFAS), a large group of manmade chemicals, have been detected extensively in the blood of people living in developed countries. Although it has been suggested that PFAS exposure might be associated with harmful effects on the brain, few studies have assessed the presence of PFAS in brain tissues. This study aimed to evaluate the concentrations of a broad range of PFAS in paired postmortem human brain and serum samples and investigate brain-to-serum concentration ratios. A partitioning experiment using PFAS-fortified animal brain samples additionally investigated differences in distribution between lipid-rich brain and water for different PFAS. Out of the 43 PFAS analyzed, 5 were detected in all paired human brain and serum samples, 11 were found in all serum, and 7 were found in all brain samples. Two PFAS compounds were observed at notably higher detection frequencies in brain samples compared to serum. The brain-to-serum ratios of PFAS concentrations ranged from approximately 0.04 for perfluorohexanesulfonate (PFHxS) to 1.3 for <i>N</i>-methyl perfluorooctanesulfonamido acetic acid (<i>N</i>-MeFOSAA) with a clear increase in PFAS brain-to-serum ratios with the total number of carbons. There were no differences between the two cortical brain regions analyzed. Results underscore the necessity of a better understanding of individual PFAS, as the difference in their properties can influence their behavior within the human brain.