Oral repeated-dose systemic and reproductive toxicity of 6:2 fluorotelomer alcohol in mice.
Oral repeated-dose systemic and reproductive toxicity of 6:2 fluorotelomer alcohol in mice.
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DOI：
10.1016/j.toxrep.2014.12.002
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发表时间：
2015
影响因子：
--
通讯作者：
O'Connor JC
中科院分区：
文献类型：
--
作者：
Mukerji P;Rae JC;Buck RC;O'Connor JC
在小鼠中评价了6：2氟调聚物醇（6：2 FTOH）的潜在全身重复给药和生殖毒性。以1、5、25或100 mg/kg/天的剂量经口灌胃给予CD-1小鼠6：2 FTOH（溶于含0.1%吐温-80的0.5%甲基纤维素水溶液中的混悬液）。基于较高剂量对死亡率、临床观察结果、体重、营养参数、血液学（红细胞和白色细胞）、临床化学（肝脏相关）、肝脏重量和组织病理学（肝脏、牙齿、生殖道和乳腺）的影响，全身毒性的无明显不良作用水平（NOAEL）为25 mg/kg/天（雄性）和5 mg/kg/天（雌性）。然而，6：2 FTOH不是选择性生殖毒物。生殖毒性的NOAEL>100 mg/kg/天;在任何剂量下均未观察到对生殖结果的影响。根据幼仔成熟延迟的临床体征以及100 mg/kg/天剂量下哺乳期幼仔存活率和幼仔体重降低，后代存活率和生长的NOAEL为25 mg/kg/天。虽然小鼠中的影响严重程度通常大于先前在CD大鼠中报告的影响严重程度，但两个种属的总体NOAEL相同，全身毒性为5 mg/kg/天，后代活力/生长为25 mg/kg/天。6：2 FTOH在两个种属中均不是选择性生殖毒物;在任何剂量水平下均未对生殖结局产生影响，在诱导母体动物死亡和重度毒性的剂量水平下，在后代中观察到任何影响。
6:2 fluorotelomer alcohol (6:2 FTOH) was evaluated for potential systemic repeated-dose and reproductive toxicity in mice. 6:2 FTOH was administered by oral gavage to CD-1 mice as a suspension in 0.5% aqueous methylcellulose with 0.1% Tween-80 at dosages of 1, 5, 25, or 100 mg/kg/day. The no-observed-adverse-effect level (NOAEL) for systemic toxicity was 25 mg/kg/day (males) and 5 mg/kg/day (females), based on effects at higher doses on mortality, clinical observations, body weight, nutritional parameters, hematology (red and white blood cell), clinical chemistry (liver-related), liver weights, and histopathology (liver, teeth, reproductive tract, and mammary gland). However, 6:2 FTOH was not a selective reproductive toxicant. The NOAEL for reproductive toxicity was >100 mg/kg/day; no effects on reproductive outcome were observed at any dosage. The NOAEL for viability and growth of the offspring was 25 mg/kg/day, based on clinical signs of delayed maturation in pups, and reductions in pup survival and pup body weight during lactation at 100 mg/kg/day. While the severity of the effects was generally greater in mice than previously reported in CD rats, the overall NOAELs were identical in both species, 5 mg/kg/day for systemic toxicity and 25 mg/kg/day for offspring viability/growth. 6:2 FTOH was not a selective reproductive toxicant in either species; no effects on reproductive outcome occurred at any dose level, and any effects observed in offspring occurred at dose levels that induced mortality and severe toxicity in maternal animals.