Vanden Heuvel J P, Kuslikis B I, Van Rafelghem M J, Peterson R E
Environmental Toxicology Center, University of Wisconsin, Madison 53706.
Toxicol Appl Pharmacol. 1991 Mar 1;107(3):450-9. doi: 10.1016/0041-008x(91)90308-2.
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.
在雄性和雌性大鼠单次腹腔注射剂量（9.4 μmol/kg，5 mg/kg）后，对[1-14C]全氟癸酸（PFDA）的消除、组织分布和代谢进行了28天的研究。观察到全氟癸酸（PFDA）粪便消除存在性别差异，处理后28天，雄性和雌性大鼠粪便中分别回收了51%和24%的给药14C。28天内，PFDA衍生的14C在尿液中的累积排泄量在两性中均小于给药剂量的5%。粪便消除速率的性别相关差异导致观察到PFDA在雄性（t1/2 = 23天）和雌性（t1/2 = 45天）体内消除半衰期的差异。肝脏中PFDA衍生的14C浓度在雄性和雌性中均最高，其次是血浆和肾脏。雄性的心脏、脂肪垫、睾丸和腓肠肌以及雌性的卵巢中PFDA浓度低得多。使用原位非循环肝脏灌注技术进一步研究了肝脏中腹腔注射剂量的[1-14C]PFDA比例高（处理后2小时，雄性为53%，雌性为41%）的原因。结果表明，灌注液中约25%的[14C]PFDA在单次通过时被肝脏提取。PFDA粪便消除性别差异的原因似乎不是胆汁排泄的性别差异。在6小时内，结扎肾脏的雄性和雌性大鼠向胆汁中排泄的[14C]PFDA剂量百分比基本相同。我们曾假设PFDA在大鼠体内的持久性是由于形成了含PFDA的脂质（即含[14C]PFDA的单酰基甘油、二酰基甘油、三酰基甘油、胆固醇酯、甲酯或磷脂）。然而，没有获得PFDA结合形成持久性杂合脂质的证据，在尿液或胆汁中也未检测到PFDA的极性代谢物。此外，PFDA处理前后雄性和雌性大鼠的每日氟排泄量相似，表明母体化合物未脱氟。因此，PFDA在雄性和雌性大鼠体内的处置特征是明显缺乏生物转化。
