Isomer-Specific Binding Affinity of Perfluorooctanesulfonate (PFOS) and Perfluorooctanoate (PFOA) to Serum Proteins

Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are among the most prominent contaminants in human serum, and these were historically manufactured as technical mixtures of linear and branched isomers. The isomers display unique pharmacokinetics in humans and in animal models, but molecular mechanisms underlying isomer-specific PFOS and PFOA disposition have not previously been studied. Here, ultrafiltration devices were used to examine (i) the dissociation constants (<i>K</i>_d) of individual PFOS and PFOA isomers with human serum albumin (HSA) and (ii) relative binding affinity of isomers in technical mixtures spiked to whole calf serum and human serum. Measurement of HSA <i>K</i>_d’s demonstrated that linear PFOS (<i>K</i>_d = 8(±4) × 10^–8 M) was much more tightly bound than branched PFOS isomers (<i>K</i>_d range from 8(±1) × 10^–5 M to 4(±2) × 10^–4 M). Similarly, linear PFOA (<i>K</i>_d = 1(±0.9) × 10^–4 M) was more strongly bound to HSA compared to branched PFOA isomers (<i>K</i>_d range from 4(±2) × 10^–4 M to 3(±2) × 10^–4 M). The higher binding affinities of linear PFOS and PFOA to total serum protein were confirmed when both calf serum and human serum were spiked with technical mixtures. Overall, these data provide a mechanistic explanation for the longer biological half-life of PFOS in humans, compared to PFOA, and for the higher transplacental transfer efficiencies and renal clearance of branched PFOS and PFOA isomers, compared to the respective linear isomer

Biomonitoring of Perfluoroalkyl Acids in Human Urine and Estimates of Biological Half-Life

Perfluoroalkyl acids (PFAAs) are persistent and bioaccumulative compounds that have been associated with adverse health outcomes. In human blood, PFAAs exist as both linear and branched isomers, yet for most linear homologues, and for all branched isomers, elimination rates are unknown. Paired blood and urine samples (<i>n</i> = 86) were collected from adults in China. They were analyzed by a sensitive isomer-specific method that permitted the detection of many PFAAs in human urine for the first time. For all PFAAs except perfluoroundecanoate (PFUnA), levels in urine correlated positively with levels in blood. Perfluoroalkyl carboxylates (PFCAs) were excreted more efficiently than perfluoroalkane sulfonates (PFSAs) of the same carbon chain-length. In general, shorter PFCAs were excreted more efficiently than longer ones, but for PFSAs, perfluorooctanesulfonate (PFOS, a C8 compound) was excreted more efficiently than perfluorohexanesulfonate (PFHxS, a C6 compound). Among PFOS and perfluorooctanoate (PFOA) isomers, major branched isomers were more efficiently excreted than the corresponding linear isomer. A one-compartment model was used to estimate the biological elimination half-lives of PFAAs. Among all PFAAs, the estimated arithmetic mean elimination half-lives ranged from 0.5 ± 0.1 years (for one branched PFOA isomer, 5<i>m</i>-PFOA) to 90 ± 11 years (for one branched PFOS isomer, 1<i>m</i>-PFOS). Urinary excretion was the major elimination route for short PFCAs (C ≤ 8), but for longer PFCAs, PFOS and PFHxS, other routes of excretion likely contribute to overall elimination. Urinary concentrations are good biomarkers of the internal dose, and this less invasive strategy can therefore be used in future epidemiological and biomonitoring studies. The very long half-lives of long-chain PFCAs, PFHxS, and PFOS isomers in humans stress the importance of global and domestic exposure mitigation strategies