Thibodeaux Julie R, Hanson Roger G, Rogers John M, Grey Brian E, Barbee Brenda D, Richards Judy H, Butenhoff John L, Stevenson Lisa A, Lau Christopher
Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Toxicol Sci. 2003 Aug;74(2):369-81. doi: 10.1093/toxsci/kfg121. Epub 2003 May 28.
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 (T4) and triiodothyronine (T3) 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 T4 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.
在大鼠和小鼠中评估了全氟辛烷磺酸（PFOS，C8F17SO3-）的母体毒性和发育毒性。PFOS是一种环境持久性化合物，用作表面活性剂，是许多商业和消费应用中发现的全氟辛烷磺酰氟和取代全氟辛烷磺酰胺成分的降解产物。从妊娠第2天（GD）至第20天，对怀孕的斯普拉格-道利大鼠每日经口灌胃给予1、2、3、5或10 mg/kg PFOS；从GD 1至GD 17，对CD-1小鼠同样给予1、5、10、15和20 mg/kg PFOS。对照组接受0.5%吐温-20赋形剂（大鼠为1 ml/kg，小鼠为10 ml/kg）。监测母体体重增加、食物和水消耗以及血清化学指标。大鼠在GD 21处死，小鼠在GD 18处死。测定母体血清以及母体和胎儿肝脏中的PFOS水平。两种动物的母体体重增加均受到PFOS的剂量依赖性抑制，这可能归因于食物和水摄入量减少。血清PFOS水平随剂量增加而升高，肝脏中的水平比血清高约四倍。在经PFOS处理的大鼠母鼠中，早在化学暴露一周后，血清甲状腺素（T4）和三碘甲状腺原氨酸（T3）就显著降低，尽管未观察到促甲状腺激素（TSH）的反馈反应。在怀孕小鼠中也观察到类似的T4降低模式。母体血清甘油三酯显著降低，尤其是在高剂量组，尽管胆固醇水平未受影响。在小鼠母鼠中，PFOS在10 mg/kg及更高剂量时可导致肝脏明显肿大。在大鼠胎儿的肝脏中检测到了PFOS，但其水平几乎是母体相应水平的一半，与给药剂量无关。在两种啮齿动物中，PFOS并未改变足月时的着床数或活胎数，尽管在大鼠中注意到胎儿体重略有不足。在大鼠和小鼠中均出现了一系列出生缺陷，包括腭裂、全身性水肿、室间隔缺损和右心房扩大，主要分别出现在10和20 mg/kg剂量组中。我们的结果证明了PFOS在大鼠和小鼠中具有母体毒性和发育毒性。
