Comparison of the toxicokinetics between perfluorocarboxylic acids with different carbon chain length.
Toxicokinetics was compared between perfluoroheptanoic acid (PFHA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in male and female rats. Half lives (t(1/2)) in male and female rats were calculated to be 0.10 and 0.05 days, respectively, for PFHA, 5.63 and 0.08 days for PFOA, 29.5 and 2.44 days for PFNA and 39.9 and 58.6 days for PFDA. Total clearance (CL(tot)) of PFHA was higher than those of other perfluorocarboxylic acids (PFCAs) in both male and female rats. By contrast, CL(tot) of PFDA was extremely low in both sexes. PFCAs having shorter carbon chain length showed higher CL(tot). There was a significant sex-related difference in CL(tot) of PFOA and PFNA. Distribution volumes in steady state (V(ss)) were not much different between PFCAs and between sexes. To estimate the role of urinary excretion in plasma clearance of PFCA, renal clearance (CL(R)) was determined for PFCAs. CL(R) of PFCAs were in the order PFHA>PFOA>PFNA approximately equal PFDA and PFHA approximately equal PFOA>PDNA>PFDA in male and female rats, respectively. There was a close relationship between CL(tot) and CL(R) (r(2)=0.981). Plasma protein binding, estimated in vitro, was over 98% for all PFCAs tested. The results indicate that CL(R) is responsible for the difference in CL(tot) between PFCAs having different carbon chain length and between sexes.
Ohmori
Kohtaro
K
Faculty of Pharmaceutical Sciences, Josai University, Keyakidai 1-1, Sakado, Saitama, Japan.
Kudo
Naomi
N
Katayama
Kazunori
K
Kawashima
Yoichi
Y
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002264:Carboxylic Acids / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D005260:Female; D006207:Half-Life; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D007668:Kidney / Q000378:metabolism; D008297:Male; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D013329:Structure-Activity Relationship
D001798:Blood Proteins; D002264:Carboxylic Acids; D006845:Hydrocarbons, Fluorinated