Two-generation reproduction and cross-foster studies of perfluorooctanesulfonate (PFOS) in rats
Two-generation reproduction and cross-foster studies of perfluorooctanesulfonate (PFOS) in rats
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DOI：
10.1016/j.tox.2005.07.018
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发表时间：
2005-11-05
期刊：
影响因子：
4.5
通讯作者：
Butenhoff, JL
中科院分区：
文献类型：
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作者：
Luebker, DJ;Case, MT;Butenhoff, JL
全氟辛烷磺酸 (PFOS) 是一种持久性酸，广泛分布于野生动物和人类体内。为了了解全氟辛烷磺酸对生殖和发育的潜在影响，在大鼠中进行了两代生殖研究。雄性和雌性大鼠在交配前、交配过程中以0、0.1、0.4、1.6和3.2mg/(kg·天)的剂量水平经口强饲，持续6周，雌性大鼠则在妊娠和哺乳期间，跨越两代。由于在 1.6 和 3.2 mg/(kg 天) 组中观察到大量 F，新生儿毒性，因此继续进入第二代的仅限于来自 0、0.1 和 0.4 mg/(kg 天) 组的 F，幼仔。在妊娠第 10 天进行剖腹产时，在 F-0 雌性或其胎儿中未观察到不良影响。在 0.4 mg/（kg 天）及更高的剂量水平下，在 F-0 代雄性和雌性中观察到体重增加和饲料消耗的统计显着减少，但在 F 成年中则不然。全氟辛烷磺酸不影响生殖性能（交配、发情周期和生育能力）；然而，F-0 母鼠在 3.2 毫克/（公斤·天）剂量下，生殖结果受到影响，表现为妊娠时间缩短、着床部位数量减少、死产幼崽或所有幼崽在哺乳期第 1-4 天死亡的母鼠数量增加。在最高测试剂量 0.4 毫克/（公斤·天）的 F 母鼠中未观察到这些效应。母体剂量为 1.6 毫克/（公斤·天）及更高剂量时，F 幼犬的新生儿毒性（通过哺乳期结束时存活率和体重增加减少而证明）发生，而在 0.1 或 0.4 毫克/（公斤·天）的剂量水平下，或在所测试的 0.1 或 0.4 毫克/（公斤·天）剂量水平的 F-2 幼犬中，发生毒性。除了这些不良影响外，F-1 幼犬在 0.4（睁眼）和 1.6 mg/（kg 天）（睁眼、空气正位、表面正位和耳廓展开）时出现轻微但具有统计学意义的发育迟缓。基于这些数据，NOAEL如下： 生殖功能：F-0≥3.2且F-1≥0.4mg/(kg·天)；生殖结果：F-0 = 1.6 且 F-1 >= 0.4 mg/(kg day)；总体亲代效应：F-0 = 0.1 且 F-1 >= 0.4 mg/（kg·天）；对后代的影响：F-0 = 0.4 且 F-1 >= 0.4 mg/(kg day)。为了区分两代研究中观察到的母犬和幼犬对围产期死亡率的影响，进行了后续的交叉寄养研究。这项研究的结果表明，在子宫内接触 PFOS 会导致产后幼犬死亡，并且产前和产后接触 PFOS 与在幼犬中观察到的毒性作用具有累加性。 (c) 2005 Elsevier Ireland Ltd. 保留所有权利。
Perfluorooctanesulfonate (PFOS) is a persistent acid found widely distributed in wildlife and humans. To understand the potential reproductive and developmental effects of PFOS, a two-generation reproduction study was conducted in rats. Male and female rats were dosed via oral gavage at dose levels of 0, 0.1, 0.4, 1.6, and 3.2 mg/(kg day) for 6 weeks prior to mating, during mating, and, for females, through gestation and lactation, across two generations. Due to substantial F, neonatal toxicity observed in the 1.6 and 3.2 mg/(kg day) groups, continuation into the second generation was limited to F, pups from the 0, 0.1, and 0.4 mg/(kg day) groups. No adverse effects were observed in F-0 females or their fetuses upon caesarean sectioning at gestation day 10. Statistically significant reductions in body-weight gain and feed consumption were observed in F-0 generation males and females at dose levels of 0.4 mg/(kg day) and higher, but not in F, adults. PFOS did not affect reproductive performance (mating, estrous cycling, and fertility); however, reproductive outcome, as demonstrated by decreased length of gestation, number of implantation sites, and increased numbers of dams with stillborn pups or with all pups dying on lactation days 1-4, was affected at 3.2 mg/(kg day) in F-0 dams. These effects were not observed in F, dams at the highest dose tested, 0.4 mg/(kg day). Neonatal toxicity in F, pups, as demonstrated by reduced survival and body-weight gain through the end of lactation, occurred at a maternal dose of 1.6 mg/(kg day) and higher while not at dose levels of 0.1 or 0.4 mg/(kg day) or in F-2 pups at the 0.1 or 0.4 mg/(kg day) dose levels tested. In addition to these adverse effects, slight yet statistically significant developmental delays occurred at 0.4 (eye opening) and 1.6 mg/(kg day) (eye opening, air righting, surface righting, and pinna unfolding) in F-1 pups. Based on these data, the NOAELs were as follows: reproductive function: F-0 >= 3.2 and F-1 >= 0.4 mg/(kg day); reproductive outcome: F-0 = 1.6 and F-1 >= 0.4 mg/(kg day); overall parental effects: F-0 = 0.1 and F-1 >= 0.4 mg/(kg day); offspring effects: F-0 = 0.4 and F-1 >= 0.4 mg/(kg day). To distinguish between maternal and pup influences contributing to the perinatal mortality observed in the two-generation study, a follow-up cross-foster study was performed. Results of this study indicated that in utero exposure to PFOS causally contributed to post-natal pup mortality, and that pre-natal and post-natal exposure to PFOS was additive with respect to the toxic effects observed in pups. (c) 2005 Elsevier Ireland Ltd. All rights reserved.