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全氟己烷磺酸钾对斯普拉格-道利大鼠潜在生殖和发育毒性的评估。

Evaluation of potential reproductive and developmental toxicity of potassium perfluorohexanesulfonate in Sprague Dawley rats.

作者信息

Butenhoff John L, Chang Shu-Ching, Ehresman David J, York Raymond G

机构信息

3M Company, Medical Department, 3M Center 220-6W-08, St. Paul, MN 55144, United States.

3M Company, Medical Department, 3M Center 220-6W-08, St. Paul, MN 55144, United States.

出版信息

Reprod Toxicol. 2009 Jun;27(3-4):331-341. doi: 10.1016/j.reprotox.2009.01.004. Epub 2009 Jan 21.

Abstract

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 10mg/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 10mg/kg-d, decreased prothrombin time; (3) at 3 and 10mg/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 10mg/kg-d, decreased triglycerides and increased albumin, BUN, ALP, Ca(2+), 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.

摘要

本研究评估了全氟己烷磺酸(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。在基于经合组织422号准则修改后的设计中,每个性别和处理组(对照组、0.3、1、3和10mg/kg·天)有15只大鼠,在同居前14天、同居期间以及直至处死前一天(雌性为21天哺乳期或假定妊娠第25天(若未怀孕),雄性为至少42天处理期),通过灌胃给予PFHxS钾盐(K⁺PFHxS)或赋形剂(0.5%羧甲基纤维素)。子代不进行灌胃给药,但在子宫内通过胎盘转运暴露,并可能通过乳汁暴露。对生殖成功率、临床体征、体重、食物消耗、发情周期、神经行为效应、选定器官的大体和微观解剖、精子、血液学、临床病理学以及血清和肝脏中PFHxS的浓度进行了评估。每组额外增加三只每个性别的大鼠,以便在研究期间获取血清和肝脏样本用于PFHxS浓度测定。未观察到生殖或发育影响。在母鼠或子代中未发现与处理相关的影响。在亲代雄鼠中观察到的K⁺PFHxS诱导的影响包括:(1)在所有剂量下,血清总胆固醇降低;(2)在0.3、3和10mg/kg·天时,凝血酶原时间缩短;(3)在3和10mg/kg·天时,肝体重比和肝脑重量比增加,小叶中央肝细胞肥大,甲状腺滤泡细胞增生,血细胞比容降低;(4)在10mg/kg·天时,甘油三酯降低,白蛋白、尿素氮、碱性磷酸酶、钙离子和白蛋白/球蛋白比值增加。报告了亲代、胎儿和幼崽的血清和肝脏中PFHxS的浓度。在研究条件下,PFHxS不是一种生殖或发育毒物。

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