Lau Christopher, Thibodeaux Julie R, Hanson Roger G, Rogers John M, Grey Brian E, Stanton Mark E, Butenhoff John L, Stevenson Lisa A
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):382-92. doi: 10.1093/toxsci/kfg122. Epub 2003 May 28.
The postnatal effects of in utero exposure to perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestation day (GD) 2 to GD 21; pregnant CD-1 mice were treated with 1, 5, 10, 15, and 20 mg/kg PFOS from GD 1 to GD 18. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). At parturition, newborns were observed for clinical signs and survival. All animals were born alive and initially appeared to be active. In the highest dosage groups (10 mg/kg for rat and 20 mg/kg for mouse), the neonates became pale, inactive, and moribund within 30-60 min, and all died soon afterward. In the 5 mg/kg (rat) and 15 mg/kg (mouse) dosage groups, the neonates also became moribund but survived for a longer period of time (8-12 h). Over 95% of these animals died within 24 h. Approximately 50% of offspring died at 3 mg/kg for rat and 10 mg/kg for mouse. Cross-fostering the PFOS-exposed rat neonates (5 mg/kg) to control nursing dams failed to improve survival. Serum concentrations of PFOS in newborn rats mirrored the maternal administered dosage and were similar to those in the maternal circulation at GD 21; PFOS levels in the surviving neonates declined in the ensuing days. Small but significant and persistent growth lags were detected in surviving rat and mouse pups exposed to PFOS prenatally, and slight delays in eye opening were noted. Significant increases in liver weight were observed in the PFOS-exposed mouse pups. Serum thyroxine levels were suppressed in the PFOS-treated rat pups, although triiodothyronine and thyroid-stimulating hormone [TSH] levels were not altered. Choline acetyltransferase activity (an enzyme that is sensitive to thyroid status) in the prefrontal cortex of rat pups exposed to PFOS prenatally was slightly reduced, but activity in the hippocampus was not affected. Development of learning, determined by T-maze delayed alternation in weanling rats, was not affected by PFOS exposure. These results indicate that in utero exposure to PFOS severely compromised postnatal survival of neonatal rats and mice, and caused delays in growth and development that were accompanied by hypothyroxinemia in the surviving rat pups.
在大鼠和小鼠中评估了子宫内暴露于全氟辛烷磺酸（PFOS，C8F17SO3-）的产后影响。从妊娠第2天（GD）至第21天，对怀孕的斯普拉格-道利大鼠每天经口灌胃给予1、2、3、5或10mg/kg的PFOS；从GD 1至GD 18，对怀孕的CD-1小鼠用1、5、10、15和20mg/kg的PFOS进行处理。对照组接受0.5%吐温-20载体（大鼠为1ml/kg，小鼠为10ml/kg）。分娩时，观察新生仔鼠的临床症状和存活率。所有动物均存活出生，最初看起来很活跃。在最高剂量组（大鼠为10mg/kg，小鼠为20mg/kg）中，新生仔鼠在30 - 60分钟内变得苍白、不活跃且濒死，随后全部死亡。在5mg/kg（大鼠）和15mg/kg（小鼠）剂量组中，新生仔鼠也变得濒死，但存活时间更长（8 - 12小时）。这些动物中超过95%在24小时内死亡。对于大鼠，约50%的后代在3mg/kg剂量下死亡；对于小鼠，在10mg/kg剂量下死亡。将暴露于PFOS的大鼠新生仔鼠（5mg/kg）寄养给对照哺乳母鼠并不能提高存活率。新生大鼠血清中PFOS浓度反映了母体给药剂量，且与GD 21时母体循环中的浓度相似；存活新生仔鼠体内的PFOS水平在随后几天下降。在产前暴露于PFOS的存活大鼠和小鼠幼崽中检测到虽小但显著且持续的生长迟缓，并注意到睁眼略有延迟。在暴露于PFOS的小鼠幼崽中观察到肝脏重量显著增加。在经PFOS处理的大鼠幼崽中血清甲状腺素水平受到抑制，尽管三碘甲状腺原氨酸和促甲状腺激素[TSH]水平未改变。产前暴露于PFOS的大鼠幼崽前额叶皮质中的胆碱乙酰转移酶活性（一种对甲状腺状态敏感的酶）略有降低，但海马体中的活性未受影响。通过断奶大鼠的T迷宫延迟交替试验确定的学习发育不受PFOS暴露的影响。这些结果表明，子宫内暴露于PFOS严重损害了新生大鼠和小鼠的产后存活率，并导致生长发育延迟，且存活的大鼠幼崽伴有低甲状腺素血症。
