Evaluation of potential reproductive and developmental toxicity of potassium perfluorohexanesulfonate in Sprague Dawley rats
Evaluation of potential reproductive and developmental toxicity of potassium perfluorohexanesulfonate in Sprague Dawley rats
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DOI：
10.1016/j.reprotox.2009.01.004
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发表时间：
2009-06-01
影响因子：
3.3
通讯作者：
York, Raymond G.
中科院分区：
文献类型：
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作者：
Butenhoff, John L.;Chang, Shu-Ching;York, Raymond G.
本研究评估了全氟己磺酸盐（PFHxS）的潜在生殖和发育毒性，PFHxS是一种在普通人群血清中发现的表面活性剂。在改进的OECD 422指南设计中，每性别15只大鼠和治疗组（对照、0.3、1、3和10 mg/kg-d）在同居前14天、同居期间和献祭前一天（雌性哺乳21天或推定妊娠第25天（如果没有怀孕），雄性治疗至少42天）灌胃PFHxS钾（K(+)PFHxS）或载药（0.5%羧甲基纤维素）。后代不通过灌胃给药，而是通过子宫内胎盘移植和可能通过乳汁接触。评估生殖成功率、临床体征、体重、食量、发情周期、神经行为效应、所选器官大体和显微解剖、精子、血液学、临床病理、血清和肝脏PFHxS浓度。在研究期间，每组每性别增加3只大鼠，以获取血清和肝脏样本进行PFHxS浓度测定。没有观察到生殖或发育方面的影响。在母鼠或后代中没有与治疗相关的影响。在亲本雄性中注意到的K(+) pfhxs诱导的效应包括：(1)在所有剂量下，血清总胆固醇降低；(2) 0.3、3和10 mg/kg-d时，凝血酶原时间缩短；(3)在3和10 mg/kg-d时，肝与体重和肝与脑重量比增加，小叶中心肝细胞肥大，甲状腺滤泡细胞增生，红细胞压积降低；(4)在10 mg/kg-d时，甘油三酯降低，白蛋白，BUN， ALP， Ca2+和A/G比升高。报告了父母、胎儿和幼崽的血清和肝脏PFHxS浓度。在研究条件下，PFHxS不是生殖或发育毒性物质。(C) 2009爱思唯尔公司版权所有。
This study evaluates the potential reproductive and developmental toxicity of perfluorohexanesulfonate (PFHxS), a surfactant found in sera of the general population. In a modified OECD 422 guideline-based design, 15 rats per sex and treatment group (control, 0.3, 1, 3, and 10 mg/kg-d) were dosed by gavage with potassium PFHxS (K(+)PFHxS) or vehicle (0.5% carboxymethylcellulose) 14 days prior to cohabitation, during cohabitation, and until the day before sacrifice (21 days of lactation or presumed gestation day 25 (if not pregnant) for females and minimum of 42 days of treatment for males). Offspring were not dosed by gavage but were exposed by placental transfer in utero and potentially exposed via milk. Evaluations were made for reproductive success, clinical signs, body weight, food consumption, estrous cycling, neurobehavioral effects, gross and microscopic anatomy of selected organs, sperm, hematology, clinical pathology, and concentration of PFHxS in serum and liver. Additional three rats per sex per group were added to obtain sera and liver samples for PFHxS concentration determinations during the study. No reproductive or developmental effects were observed. There were no treatment-related effects in dams or offspring. K(+)PFHxS-induced effects noted in parental males included: (1) at all doses, reductions in serum total cholesterol; (2) at 0.3,3, and 10 mg/kg-d, decreased prothrombin time; (3) at 3 and 10 mg/kg-d, increased liver-to-body weight and liver-to-brain weight ratios, centrilobular hepatocellular hypertrophy, hyperplasia of thyroid follicular cells, and decreased hematocrit: (4) at 10 mg/kg-d, decreased triglycerides and increased albumin, BUN, ALP, Ca2+, and A/G ratio. Serum and liver concentrations of PFHxS are reported for parents, fetuses, and pups. PFHxS was not a reproductive or developmental toxicant under study conditions. (C) 2009 Elsevier Inc. All rights reserved.