Binding of perfluorooctanoic acid to rat and human plasma proteins.
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.
Han
Xing
X
DuPont Haskell Laboratory for Health and Environmental Sciences, PO Box 50, Newark, Delaware 19714, USA. xing.han@usa.dupont.com
Snow
Timothy A
TA
Kemper
Raymond A
RA
Jepson
Gary W
GW
D000284:Administration, Oral; D000818:Animals; D001665:Binding Sites; D002210:Caprylates / Q000008:administration & dosage / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002850:Chromatography, Gel; D005260:Female; D005466:Fluorocarbons / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D008297:Male; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization
D002210:Caprylates; D002250:Carbon Radioisotopes; D005466:Fluorocarbons; D012709:Serum Albumin; C023036:perfluorooctanoic acid