Urine-to-Blood Partitioning of Per- and Polyfluoroalkyl Substances in Human Biomonitoring: Implications for...

Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals with substantial bioaccumulation potential, but their distribution between blood and urine in humans remains poorly characterized. In this review, we assessed the urine-to-blood concentration ratio (UtBCR) as a potential indicator of PFAS bioaccumulation by integrating evidence from human biomonitoring studies and protein-binding data. We summarized PFAS concentrations in human serum and urine across general and highly exposed populations and identified clear compound-specific differences in blood-urine partitioning. We further examined the associations of UtBCR with carbon chain length, biological half-life, and binding-related parameters for human serum albumin (HSA), liver fatty acid-binding protein (L-FABP), and several renal transporters. Pairwise correlation analysis and partial least squares regression indicated that UtBCR was closely associated with major toxicokinetic determinants, particularly protein-binding affinity, carbon chain length, and biological half-life. Parameters related to FABP, HSA, urate transporter 1 (URAT1), and organic anion transporter 4 (OAT4) showed more consistent associations with UtBCR than those related to organic anion transporters 1(OAT1) and organic anion transporter 3 (OAT3), suggesting that plasma/tissue binding and tubular reabsorption may contribute more than active tubular secretion to PFAS blood-urine partitioning. Overall, UtBCR appears to be a useful toxicokinetic metric for comparing the relative bioaccumulation potential of PFAS.