Binding of Perfluorooctanoic Acid to Rat and Human Plasma Proteins

TLDR

PFOA is a widely used fluorochemical with a long half‑life in human blood. The study examined PFOA binding to rat and human plasma proteins. PFOA binding to serum albumin was characterized by electrospray ionization mass spectrometry and microdesalting‑based dissociation constant measurements. PFOA binds predominantly to serum albumin with a dissociation constant of ~0.3–0.4 mM, yielding ~6–9 binding sites and resulting in >90 % of circulating PFOA being albumin‑bound in both rats and humans.

Abstract

Perfluorooctanoic acid (PFOA) is a commercially important organic fluorochemical and is considered to have a long half-life in human blood. In this paper, PFOA binding to rat and human plasma proteins was investigated. On the basis of results from size-exclusion chromatography and ligand blotting, most PFOA was in protein-bound form in male and female rat plasma, and the primary PFOA binding protein in plasma was serum albumin. PFOA binding to rat serum albumin (RSA) in the gas phase was observed by electrospray ionization MS. 19F NMR experiments revealed that binding to RSA caused peak broadening and chemical shift changes of PFOA resonances, and on the basis of this observation, the dissociation constant was determined to be ∼0.3 mM. The dissociation constants for PFOA binding to RSA and human serum albumin (HSA) and the numbers of PFOA binding sites on RSA and HSA were also determined by a separation method using microdesalting columns. No significant difference was found between PFOA binding to RSA and PFOA binding to HSA. The dissociation constants for binding of PFOA to RSA or HSA and the numbers of PFOA binding sites were in the range of 0.3−0.4 mM and 6−9, respectively. On the basis of these binding parameters and the estimated plasma concentration of serum albumin, greater than 90% of PFOA would be bound to serum albumin in both rat and human blood.