Disposition of perfluorodecanoic acid in male and female rats.
Disposition of perfluorodecanoic acid in male and female rats.
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DOI：
10.1016/0041-008x(91)90308-2
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发表时间：
1991-03
影响因子：
3.8
通讯作者：
John P. Vanden Heuvel;Benedict I. Kuslikis;M. J. Rafelghem;R. E. Peterson
中科院分区：
文献类型：
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作者：
John P. Vanden Heuvel;Benedict I. Kuslikis;M. J. Rafelghem;R. E. Peterson
单次ip给药（9.4 μmol/kg，5 mg/kg）后28天，在雄性和雌性大鼠中检查了[1- 14 C]PFDA的消除、组织分布和代谢。全氟癸酸（PFDA）的粪便消除存在性别差异，在给药后28天，雄性和雌性大鼠的粪便中分别回收了51%和24%的14 C。在两种性别动物中，28天内尿液中PFDA衍生14 C的累积排泄量均小于给药剂量的5%。粪便消除率的性别相关差异导致雄性（t1 2 = 23天）和雌性（t1 2 = 45天）中观察到的PFDA全身消除t1 2差异。在雄性和雌性动物中，肝脏中含有最高浓度的PFDA衍生14 C，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的浓度要低得多。使用原位非再循环肝脏灌注技术进一步检查了肝脏中[1- 14 C]PFDA ip剂量百分比较高的原因（53%雄性和41%雌性，给药后2 h）。结果表明，灌注液中约25%的[14 C]PFDA在单次通过中被肝脏提取。PFDA粪便消除的性别差异的基础似乎不是由于胆汁排泄的性别差异。在6小时的时间内，肾脏结扎的雄性和雌性大鼠将基本相同百分比剂量的[14 C]PFDA释放到胆汁中。我们假设PFDA在大鼠中的持久性是由于形成了含PFDA的脂质（即，含[14 C] PFDA的单-、二-或三酰基甘油、胆固醇酯、甲酯或磷脂）。然而，没有证据表明PFDA结合形成持久的混合脂质，也没有在尿液或胆汁中检测到PFDA的极性代谢物。此外，在PFDA治疗前后，雄性和雌性大鼠的每日尿氟排泄量相似，表明母体化合物未脱氟。因此，PFDA在雄性和雌性大鼠中的分布特征为明显缺乏生物转化。
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 μmol/kg, 5 mg/kg). A sex difference in the fecal elimination of perfluorodecanoic acid (PFDA) was observed with 51 and 24% of the administered14C being recovered in the feces of male and female rats, respectively, by 28 days post-treatment. The cumulative excretion of PFDA-derived14C 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 t 1 2 of PFDA in males (t 1 2 = 23 days ) and females (t 1 2 = 45 days ). The liver contained the highest concentration of PFDA-derived14C 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 ȩliminated 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.