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 (CLtot) of PFHA was higher than those of other perfluorocarboxylic acids (PFCAs) in both male and female rats. By contrast, CLtot of PFDA was extremely low in both sexes. PFCAs having shorter carbon chain length showed higher CLtot. There was a significant sex-related difference in CLtot 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 (CLR) was determined for PFCAs. CLR of PFCAs were in the order PFHA > PFOA > PFNA similar or equal to PFDA and PFHA similar or equal to PFOA > PDNA > PFDA in male and female rats, respectively. There was a close relationship between CLtot and CLR (r(2) = 0.981). Plasma protein binding, estimated in vitro, was over 98% for all PFCAs tested. The results indicate that CLR is responsible for the difference in CLtot between PFCAs having different carbon chain length and between sexes. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.