Vanden Heuvel, JP; Kuslikis, BI; Van Rafelghem, MJ; Peterson, RE
The elimination, tissue distribution, and metabolism of [1-14C]PFDA were examined in male and female rats for 28 days after a single ip dose (9.4 mumol/kg, 5 mg/kg). A sex difference in the fecal elimination of perfluorodecanoic acid (PFDA) was observed with 51 and 24% of the administered 14C being recovered in the feces of male and female rats, respectively, by 28 days post-treatment. The cumulative excretion of PFDA-derived 14C in the urine in 28 days was less than 5% of the administered dose in both sexes. The sex-related difference in the rate of fecal elimination resulted in the observed difference in whole body elimination t1/2 of PFDA in males (t1/2 = 23 days) and females (t1/2 = 45 days). The liver contained the highest concentration of PFDA-derived 14C in both males and females, followed by the plasma and kidneys. The heart, fat pads, testes, and gastrocnemius muscle of males, and the ovaries of females contained much lower concentrations of PFDA. The reason for the high percentage of the ip dose of [1-14C]PFDA in the liver (53% males and 41% females, 2 hr post-treatment) was further examined using an in situ nonrecirculating liver perfusion technique. It was shown that approximately 25% of the [14C]PFDA in the perfusate was extracted by the liver in a single pass. The basis for the sex difference in fecal elimination of PFDA does not appear to be due to a sex difference in biliary excretion. In a 6-hr period, male and female rats with kidneys ligated eliminated essentially the same percentage dose of [14C]PFDA into bile. We had hypothesized that the persistence of PFDA in rats was due to formation of a PFDA-containing lipid (i.e., a [14C]PFDA-containing mono-, di-, or triacylglycerol, cholesteryl ester, methyl ester, or phospholipid). However, no evidence that PFDA is conjugated to form persistent hybrid lipids was obtained, nor were polar metabolites of PFDA detected in urine or bile. In addition, daily urinary excretion of fluoride in male and female rats before and after PFDA treatment was similar, suggesting that the parent compound is not defluorinated. Thus, the disposition of PFDA in male and female rats is characterized by an apparent lack of biotransformation.
