Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. I: Maternal and prenatal evaluations
Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. I: Maternal and prenatal evaluations
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DOI：
10.1093/toxsci/kfg121
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发表时间：
2003-08-01
影响因子：
3.8
通讯作者：
Lau, C
中科院分区：
文献类型：
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作者：
Thibodeaux, JR;Hanson, RG;Lau, C
在大鼠和小鼠中评价了全氟辛烷磺酸（PFOS，C8 F17 SO 3-）的母体毒性和发育毒性。全氟辛烷磺酸是一种用作表面活性剂的环境持久性化合物，是全氟辛基磺酰氟和取代的全氟辛基磺酰氨基成分的降解产物，在许多商业和消费应用中发现。从妊娠第2天至妊娠第20天，每天对妊娠Sprague-Dawley大鼠灌胃1、2、3、5或10毫克/千克的全氟辛烷磺酸;从妊娠第1天至妊娠第17天，对CD-1小鼠进行类似的全氟辛烷磺酸灌胃，剂量为1、5、10、15和20毫克/千克。对照组接受0.5%吐温-20溶剂（大鼠为1 ml/kg，小鼠为10 ml/kg）。监测母体体重增加、摄食量和饮水量以及血清化学。在GD 21处死大鼠，在GD 18处死小鼠。测定了母体血清以及母体和胎儿肝脏中的全氟辛烷磺酸水平。全氟辛烷磺酸以剂量依赖的方式抑制了这两个物种的母体体重增加，这可能是由于食物和水摄入量减少。血清中的全氟辛烷磺酸水平随着剂量的增加而增加，肝脏中的全氟辛烷磺酸水平大约是血清中的四倍。在接触化学品一周后，接受全氟辛烷磺酸处理的母鼠的血清甲状腺素（T-4）和三碘甲状腺原氨酸（T-3）显著降低，但未观察到促甲状腺激素（TSH）的反馈反应。在妊娠小鼠中也观察到类似的T-4减少模式。母体血清甘油三酯显著降低，尤其是在高剂量组中，但胆固醇水平未受影响。在10毫克/千克或更高剂量下，全氟辛烷磺酸会使母鼠的肝脏明显增大。在大鼠胎儿的肝脏中检测到全氟辛烷磺酸，但无论给药剂量如何，其含量都接近母体的一半。在这两种啮齿类动物中，全氟辛烷磺酸并未改变足月妊娠或活胎的数量，尽管在大鼠中发现了胎儿体重的轻微不足。在大鼠和小鼠中观察到许多出生缺陷，包括腭裂、全身水肿、室间隔缺损和右心房增大，主要分别在10和20 mg/kg剂量组中。我们的研究结果表明，全氟辛烷磺酸对大鼠和小鼠具有母体毒性和发育毒性。
The maternal and developmental toxicities of perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. PFOS is an environmentally persistent compound used as a surfactant and occurs as a degradation product of both perfluorooctane sulfonyl fluoride and substituted perfluorooctane sulfonamido components found in many commercial and consumer applications. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestational day (GD) 2 to GD 20; CD-1 mice were similarly treated with 1, 5, 10, 15, and 20 mg/kg PFOS from GD 1 to GD 17. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). Maternal weight gain, food and water consumption, and serum chemistry were monitored. Rats were euthanized on GD 21 and mice on GD 18. PFOS levels in maternal serum and in maternal and fetal livers were determined. Maternal weight gains in both species were suppressed by PFOS in a dose-dependent manner, likely attributed to reduced food and water intake. Serum PFOS levels increased with dosage, and liver levels were approximately fourfold higher than serum. Serum thyroxine (T-4) and triiodothyronine (T-3) in the PFOS-treated rat dams were significantly reduced as early as one week after chemical exposure, although no feedback response of thyroid-stimulating hormone (TSH) was observed. A similar pattern of reduction in T-4 was also seen in the pregnant mice. Maternal serum triglycerides were significantly reduced, particularly in the high-dose groups, although cholesterol levels were not affected. In the mouse dams, PFOS produced a marked enlargement of the liver at 10 mg/kg and higher dosages. In the rat fetuses, PFOS was detected in the liver but at levels nearly half of those in the maternal counterparts, regardless of administered doses. In both rodent species, PFOS did not alter the numbers of implantations or live fetuses at term, although small deficits in fetal weight were noted in the rat. A host of birth defects, including cleft palate, anasarca, ventricular septal defect, and enlargement of the right atrium, were seen in both rats and mice, primarily in the 10 and 20 mg/kg dosage groups, respectively. Our results demonstrate both maternal and developmental toxicity of PFOS in the rat and mouse.