Toxicity Evaluation of Bisphenol A Administered by Gavage to Sprague Dawley Rats From Gestation Day 6 Through Postnatal Day 90
Toxicity Evaluation of Bisphenol A Administered by Gavage to Sprague Dawley Rats From Gestation Day 6 Through Postnatal Day 90
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DOI：
10.1093/toxsci/kfu022
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发表时间：
2014-05-01
影响因子：
3.8
通讯作者：
Thorn, Brett T.
中科院分区：
文献类型：
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作者：
Delclos, K. Barry;Camacho, Luisa;Thorn, Brett T.
双酚 A (BPA) 是一种高产量的工业化学品，人类通过口腔广泛接触。用于设定监管限值的指南研究仅在远高于人类暴露剂量的剂量下检测到不良反应，并建立了 5 毫克/公斤体重 (bw)/天的未观察到不良反应水平 (NOAEL)。然而，许多报道的动物研究表明，在低于 NOAEL 的剂量下，BPA 会对多个器官系统产生潜在的不利影响。本文报告的亚慢性研究的主要目标是确定口服（强饲）BPA 低于 NOAEL 引起的不良反应，表征此类效应的剂量反应，并确定后续慢性研究的剂量。 Sprague Dawley 母鼠从妊娠第 6 天到临产开始每天给药，幼鼠从出生后第 1 天到终止直接给药。主要焦点是七种等距的 BPA 剂量（2.5-2700 微克/公斤体重/天）。还包括一个天然对照、两个剂量的乙炔雌二醇（EE2）以证明动物模型的雌激素反应性，以及指导研究预计会产生不良影响的两个高 BPA 剂量（100,000 和 300,000 微克/千克体重/天）。仅在两次高剂量 BPA 时观察到 BPA 的明显不良反应，包括妊娠期和产后体重增加抑制、对卵巢的影响（囊性卵泡增加、黄体和窦卵泡减少）以及血清激素（血清雌二醇和催乳素增加，黄体酮减少）。 BPA 诱导的作用与 EE2 诱导的作用部分重叠，这与已知的 BPA 弱雌激素活性一致。
Bisphenol A (BPA) is a high production volume industrial chemical to which there is widespread human oral exposure. Guideline studies used to set regulatory limits detected adverse effects only at doses well above human exposures and established a no-observed-adverse-effect level (NOAEL) of 5 mg/kg body weight (bw)/day. However, many reported animal studies link BPA to potentially adverse effects on multiple organ systems at doses below the NOAEL. The primary goals of the subchronic study reported here were to identify adverse effects induced by orally (gavage) administered BPA below the NOAEL, to characterize the dose response for such effects and to determine doses for a subsequent chronic study. Sprague Dawley rat dams were dosed daily from gestation day 6 until the start of labor, and their pups were directly dosed from day 1 after birth to termination. The primary focus was on seven equally spaced BPA doses (2.5-2700 mu g/kg bw/day). Also included were a na < ve control, two doses of ethinyl estradiol (EE2) to demonstrate the estrogen responsiveness of the animal model, and two high BPA doses (100,000 and 300,000 mu g/kg bw/day) expected from guideline studies to produce adverse effects. Clear adverse effects of BPA, including depressed gestational and postnatal body weight gain, effects on the ovary (increased cystic follicles, depleted corpora lutea, and antral follicles), and serum hormones (increased serum estradiol and prolactin and decreased progesterone), were observed only at the two high doses of BPA. BPA-induced effects partially overlapped those induced by EE2, consistent with the known weak estrogenic activity of BPA.