Battelle, Pacific Northwest National Laboratory, Marine Science Laboratory, 1529 West Sequim Bay Road, Sequim, Washington 98382, USA.
Environ Sci Technol. 2010 Jan 1;44(1):491-6. doi: 10.1021/es901838y.
Perfluorooctanoic acid (PFOA) among other perfluorinated acids is becoming recognized as a ubiquitous environmental contaminant. PFOA is resistant to environmental degradation and appears to undergo no biotransformation in animals. Previous toxicokinetic studies in rodents have indicated that urinary excretion is the most important elimination pathway once PFOA has been absorbed. In some species such as rats, large sex-related differences in urinary excretion have been reported, with females having a much shorter blood or plasma elimination half-life than that of males. It is unknown whether this phenomenon occurs in fish. Therefore, this study determined the disposition of PFOA in male and female fathead minnows (Pimephales promelas) after a single oral dose of PFOA. After dosing, minnows were subsequently euthanized at various times until 336 h postdosing and the PFOA concentration was measured in plasma, gonads, and fish carcass. The concentration-time profiles of PFOA were then analyzed using toxicokinetic methods. The results indicated a clear sex difference in the elimination of PFOA. The plasma elimination half-life of PFOA in female minnows was 6.3 h while in male minnows it was 68.5 h. Pretreatment of female minnows with the synthetic androgen trenbolone substantially delayed the elimination of PFOA, causing the elimination half-life to increase to 25.3 h. In males, pretreatment with the synthetic estrogen ethynylestradiol (EE2) had little effect on PFOA toxicokinetics. These results indicate that the sex differences in PFOA elimination in fathead minnows can at least partially be modulated by exposure to synthetic sex steroids. Whether sex differences in PFOA elimination in minnows is attributable to differences in renal transport activity, as it appears to be for rodents, is unknown at present but clearly warrants further study.
全氟辛酸（PFOA）和其他全氟羧酸一样，正逐渐被认为是一种普遍存在的环境污染物。PFOA 不易被环境降解，似乎在动物体内不会发生生物转化。以前在啮齿动物中的毒代动力学研究表明，一旦 PFOA 被吸收，尿液排泄是最重要的消除途径。在某些物种（如大鼠）中，已报道了尿液排泄存在较大的性别差异，雌性的血液或血浆消除半衰期明显短于雄性。目前尚不清楚这种现象是否发生在鱼类中。因此，本研究测定了雄性和雌性褐鳟（Pimephales promelas）单次口服 PFOA 后的 PFOA 分布情况。给药后，在不同时间点处死小鱼，直到给药后 336 小时，并测量血浆、性腺和鱼体中的 PFOA 浓度。然后使用毒代动力学方法分析 PFOA 的浓度-时间曲线。结果表明，PFOA 的消除存在明显的性别差异。雌性褐鳟血浆中 PFOA 的消除半衰期为 6.3 小时，而雄性褐鳟为 68.5 小时。雌性褐鳟预先用合成雄激素 trenbolone 处理可明显延迟 PFOA 的消除，导致消除半衰期增加至 25.3 小时。而雄性褐鳟预先用合成雌激素乙炔雌二醇（EE2）处理对 PFOA 的毒代动力学影响不大。这些结果表明，褐鳟体内 PFOA 消除的性别差异至少部分可通过暴露于合成性激素来调节。目前尚不清楚褐鳟中 PFOA 消除的性别差异是否归因于肾脏转运活性的差异，就像在啮齿动物中那样，但显然值得进一步研究。
