Prenatal Perfluorooctanoic Acid Exposure in CD-1 Mice: Low-Dose Developmental Effects and Internal Dosimetry
Prenatal Perfluorooctanoic Acid Exposure in CD-1 Mice: Low-Dose Developmental Effects and Internal Dosimetry
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DOI：
10.1093/toxsci/kfr076
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发表时间：
2011-07-01
影响因子：
3.8
通讯作者：
Fenton, Suzanne E.
中科院分区：
文献类型：
--
作者：
Macon, Madisa B.;Villanueva, LaTonya R.;Fenton, Suzanne E.
全氟辛酸（PFOA）是一种环境污染物，会对实验室动物的发育造成不良影响。为了研究低剂量PFOA对后代的影响，对定时怀孕的CD-1小鼠在整个妊娠期或妊娠期的一半时间内灌胃给予PFOA。在整个妊娠期研究中，小鼠从妊娠期（GD）第1-17天每天分别服用0、0.3、1.0和3.0毫克全氟辛酸/千克体重（BW）。在妊娠后期研究中，小鼠从GD 10-17开始每天给予0、0.01、0.1和1.0 mg PFOA/kg BW。在整个妊娠期研究中，暴露于PFOA显著（p < 0.05）增加了所有治疗组和妊娠后期研究中1.0 mg PFOA/kg组的后代相对肝脏重量。在这两项研究中，通过发育评分评估，所有接受PFOA治疗的母鼠的后代均表现出乳腺上皮生长显著受阻。在出生后第21天，与对照组相比，1.0 mg/kg GD 10-17组的乳腺具有显著较少的纵向上皮生长和较少的末端芽（p < 0.05）。对后代体内剂量测定的评价显示，肝脏和血清中的全氟辛酸浓度在长达6周的时间内一直保持较高水平，而大脑中的浓度在4周后很低，无法检测到。这些数据表明，在CD-1小鼠中，全氟辛酸对乳腺组织的诱导效应（1）发生在比对肝脏重量的影响更低的剂量下，这一观察结果可能具有品系特异性，（2）持续到妊娠期暴露后12周龄。由于CD-1小鼠乳腺对PFOA的敏感性较低，因此在这些研究中未发现乳腺发育迟缓的无明显不良影响水平。
Perfluorooctanoic acid (PFOA) is an environmental contaminant that causes adverse developmental effects in laboratory animals. To investigate the low-dose effects of PFOA on offspring, timed-pregnant CD-1 mice were gavage dosed with PFOA for all or half of gestation. In the full-gestation study, mice were administered 0, 0.3, 1.0, and 3.0 mg PFOA/kg body weight (BW)/day from gestation days (GD) 1-17. In the late-gestation study, mice were administered 0, 0.01, 0.1, and 1.0 mg PFOA/kg BW/day from GD 10-17. Exposure to PFOA significantly (p < 0.05) increased offspring relative liver weights in all treatment groups in the full-gestation study and in the 1.0 mg PFOA/kg group in the late-gestation study. In both studies, the offspring of all PFOA-treated dams exhibited significantly stunted mammary epithelial growth as assessed by developmental scoring. At postnatal day 21, mammary glands from the 1.0 mg/kg GD 10-17 group had significantly less longitudinal epithelial growth and fewer terminal end buds compared with controls (p < 0.05). Evaluation of internal dosimetry in offspring revealed that PFOA concentrations remained elevated in liver and serum for up to 6 weeks and that brain concentrations were low and undetectable after 4 weeks. These data indicate that PFOA-induced effects on mammary tissue (1) occur at lower doses than effects on liver weight in CD-1 mice, an observation that may be strain specific, and (2) persist until 12 weeks of age following full-gestational exposure. Due to the low-dose sensitivity of mammary glands to PFOA in CD-1 mice, a no observable adverse effect level for mammary developmental delays was not identified in these studies.