Binding of Perfluorooctanoic Acid to Rat and Human Plasma Proteins

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. (19)F 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 approximately 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.

Determinants of maternal and fetal exposure and temporal trends of perfluorinated compounds

“…PFCs are distributed mainly to the liver and blood where they bind to serum proteins, mainly albumin (Han et al 2003;Jones et al 2003), and they are poorly eliminated in humans and have serum half-lives between 2 and 9 years (Lau et al 2007;Olsen et al 2007;Bartell et al 2010;Brede et al 2010;Seals et al 2011).…”

Fluorescence study on site-specific binding of perfluoroalkyl acids to human serum albumin

“…Based on these results as well as environmental and human exposure concentrations of PFOS, it was concluded that the chemical would not displace hormones from serum proteins. In another report by Han et al (2003), binding of PFOA to rat and human plasma proteins were investigated. From sizeexclusion and ligand-blotting experiments, it was found that PFOA bound primarily to serum albumin in plasma.…”

Assessment of lipid, hepatic, and thyroid parameters with serum perfluorooctanoate (PFOA) concentrations in fluorochemical production workers

“…Worker EKG results and C-reactive protein measurements were also not associated with PFOA. Although Kaplan offered no additional hypotheses or suggested causal models (Hernán et al 2002), PFOA has been shown to bind or be carried on blood albumin (Han et al 2003) and beta-lipoproteins (KerstnerWood et al 2003) in the rat, monkey and human; thus, a positive non-causal correlation remains a possibility.…”