Preferential distribution of long-chain perfluoroalkyl acids (PFAAs) in the liver, kidney, and blood of organisms highlights the importance of PFAA-protein interactions in PFAA tissue distribution patterns. A serum protein association constant may be a useful parameter to characterize the bioaccumulative potential and in vivo bioavailability of PFAAs. In this work, association constants (K(a)) and binding stoichiometries for PFAA-albumin complexes are quantified over a wide range of PFAA:albumin mole ratios. Primary association constants for perfluorooctanoate (PFOA) or perfluorononanoate (PFNA) with the model protein bovine serum albumin (BSA) determined via equilibrium dialysis are on the order of 10(6) M(-1) with one to three primary binding sites. PFNA was greater than 99.9% bound to BSA or human serum albumin (HSA) at a physiological PFAA:albumin mole ratio (<10(-3)), corresponding to a high protein-water distribution coefficient (log K(PW) > 4). Nanoelectrospray ionization mass spectrometry (nanoESI-MS) data reveal PFAA-BSA complexes with up to eight occupied binding sites at a 4:1 PFAA:albumin mole ratio. Association constants estimated by nanoESI-MS are on the order of 10(5) M(-1) for PFOA and PFNA and 10(4) M(-1) for perfluorodecanoate and perfluorooctanesulfonate. The results reported here suggest binding through specific high affinity interactions at low PFAA:albumin mole ratios.

Perfluorochemicals are globally pervasive contaminants that are persistent, bioaccumulative, and toxic. Perfluorocarboxylic acids (PFCAs) with 8-13 carbons accumulate in the liver and blood of aquatic organisms; PFCA-protein interactions may explain this accumulation pattern. Here, the interactions between PFCAs with 8-11 carbons and serum albumin are examined using three experimental approaches: surface tension titrations, (19)F NMR spectroscopy, and fluorescence spectroscopy. Surface tension titrations indicate complex formation at high (mM) PFCA concentrations. Secondary association constants ranging from 10(2) to 10(4) M(-1) were determined from (19)F NMR titrations at high PFCA:albumin mole ratios. Fluorescence measurements indicate that PFCA-albumin interactions alter the protein conformation at low PFCA:albumin mole ratios (up to 5:1) and suggest two binding classes with association constants around 10(5) and 10(2) M(-1). While (19)F NMR and fluorescence provide both qualitative and quantitative information about PFCA-albumin interactions, surface tension provides only qualitative information. Limitations associated with instrumentation and methods require high PFCA concentrations in both surface tension and (19)F NMR experiments; in contrast, fluorescence allows for analysis of a wider range of PFCA concentrations and PFCA:albumin mole ratios. Results from this study indicate that fluorescence, though an indirect method, offers a more comprehensive picture of the nature of PFCA-albumin interactions.

Interactions of perfluoroalkyl acids (PFAAs) with tissue and serum proteins likely contribute to their tissue distribution and bioaccumulation patterns. Protein-water distribution coefficients (K(PW) ) based on ligand associations with bovine serum albumin (BSA) as a model protein were recently proposed as biologically relevant parameters to describe the environmental behavior of PFAAs, yet empirical data on such protein binding behavior are limited. In the present study, associations of perfluoroalkyl carboxylates (PFCAs) with two to 12 carbons (C₂-C₁₂) and perfluoroalkyl sulfonates with four to eight carbons (C₄, C₆, and C₈) with BSA are evaluated at low PFAA:albumin mole ratios and various solution conditions using equilibrium dialysis, nanoelectrospray ionization mass spectrometry, and fluorescence spectroscopy. Log K(PW) values for C₄ to C₁₂ PFAAs range from 3.3 to 4.3. Affinity for BSA increases with PFAA hydrophobicity but decreases from the C₈ to C₁₂ PFCAs, likely due to steric hindrances associated with longer and more rigid perfluoroalkyl chains. The C₄-sulfonate exhibits increased affinity relative to the equivalent chain-length PFCA. Fluorescence titrations support evidence that an observed dependence of PFAA-BSA binding on pH is attributable to conformational changes in the protein. Association constants determined for perfluorobutanesulfonate and perfluoropentanoate with BSA are on the order of those for long-chain PFAAs (K(a) ∼10⁶/M), suggesting that physiological implications of strong binding to albumin may be important for short-chain PFAAs.

Understanding virus transfer between liquid and skin is necessary to estimate transmission during water-related activities. Here, we modeled virus transfer from liquid-to-skin and skin-to-liquid. We performed human subject studies using three bacteriophages as pathogenic virus surrogates: nonenveloped MS2 and Qβ and enveloped Φ6. Our study shows that transfer from liquid-to-skin is describable by a single model based on (1) virus concentration and (2) volume of liquid remaining on skin. Contact times (0.1-30 min), and virus species had little-to-no influence on virus transfer. Likewise, liquid conditions (pH 6-9, ionic strength 10-550 mM) had no influence on transfer as shown for MS2. The model accounts for both, virus adsorbed onto the skin, and virus in the liquid retained on skin. In comparison, virus transfer from skin-to-liquid was influenced by the wetness of the skin and by liquid type (water, saliva). 90 ± 19% of the virus inoculated on the skin are transferred to the water when the skin remains wet compared to 30 ± 17% when the skin is dry. The transfer from skin-to-liquid was 41% higher when the recipient liquid was water as compared with saliva. This study quantifies virus transfer between liquid and skin and guides risk assessments of water-related activities.