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首页> 外文期刊>Archives of Toxicology >Toxicokinetics of bisphenol A in female DA/Han rats after a single i.v. and oral administration.
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Toxicokinetics of bisphenol A in female DA/Han rats after a single i.v. and oral administration.

机译：单次静脉内注射后双酚A在雌性DA / Han大鼠中的毒代动力学和口服。

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Bisphenol A [BPA; 2,2-bis-(4-hydroxyphenyl)-propane] is a monomer used in the manufacture of resins with a wide range of applications, e.g. plastic coatings in the food packaging industry. BPA has been shown to have a weak oestrogenic activity in vitro and in vivo. Despite its low oestrogenic potency there is concern that, as a consequence of slow clearance, BPA might reach biologically significant levels in humans and animals exposed to environmental levels. To address this concern, we assessed the kinetic behaviour of BPA in female DA/Han rats. Groups of female rats received 10 mg BPA/kg body weight intravenously or 10 or 100 mg BPA/kg body weight orally (by gavage). Blood samples were collected at different time-points and plasma was prepared. Free BPA in the samples was isolated by fluid-fluid extraction. BPA was measured by GC-MS which allowed the reliable determination of BPA concentrations as low as approximately 10 ng/ml plasma. Immediately after i.v. administration, the BPA plasma concentration was in the range of about 15 microg/ml and decreased rapidly within the first hour (to 700 ng/ml). The levels declined further (100 ng/ml at 2 h), and after 24 h the analytical detection limit was reached. BPA was detected in plasma as early as 10 min after gavage administration, indicating rapid initial uptake from the gastrointestinal tract. Absorption of BPA was variable. In animals receiving 10 mg/kg, maximal plasma levels were reached after 1.5 h (31 ng/ ml) and 6 h (40 ng/ml). In animals receiving 100 mg/kg, plasma levels reached maxima around 30 min (150 ng/ml) and 3 h (134 ng/ml) after administration. After 48 h BPA was at or below the detection limit in both dose groups. Fluctuations in the BPA plasma concentrations over time point to the possibility of enterohepatic recirculation and protracted absorption from the gastrointestinal tract. Using the area under the concentration-time curves (AUCs), low bioavailabilities of 16.4% and 5.6% were calculated for the 10 and 100 mg/kg dose groups, respectively. The toxicokinetic properties of BPA in DA/Han rats are in agreement with the hypothesis of a rapid first-pass elimination by the liver and efficient metabolic clearance of low oral doses. Only excessive doses may lead to bioaccumulation if detoxification pathways are saturated.
机译：双酚A [BPA; 2，2-双-（4-羟苯基）-丙烷]是一种用于制造具有广泛应用范围的树脂的单体，例如丙烯酸。食品包装工业中的塑料涂料。已证明BPA在体外和体内均具有弱的雌激素活性。尽管其雌激素效能低，但人们担心，由于清除缓慢，BPA可能在暴露于环境水平的人和动物中达到生物学上的显着水平。为了解决这个问题，我们评估了雌性DA / Han大鼠中BPA的动力学行为。雌性大鼠组静脉内接受10 mg BPA / kg体重或口服（通过管饲）接受10或100 mg BPA / kg体重。在不同时间点采集血样并制备血浆。通过流体萃取分离样品中的游离BPA。 BPA通过GC-MS测量，可以可靠地测定低至约10 ng / ml血浆的BPA浓度。在i.v.之后给药后，BPA血浆浓度在约15微克/毫升的范围内，并在第一小时内迅速下降（降至700纳克/毫升）。该水平进一步下降（在2 h时为100 ng / ml），并在24 h后达到分析检测极限。早在管饲法给药后10分钟就在血浆中检测到BPA，这表明胃肠道迅速吸收了BPA。 BPA的吸收是可变的。在接受10 mg / kg的动物中，在1.5 h（31 ng / ml）和6 h（40 ng / ml）后达到最大血浆水平。在接受100 mg / kg的动物中，给药后约30分钟（150 ng / ml）和3 h（134 ng / ml）的血浆水平达到最大值。 48小时后，两个剂量组的BPA均在或低于检测极限。随着时间的流逝，BPA血浆浓度的波动表明可能存在肠肝再循环和胃肠道吸收延长。使用浓度-时间曲线（AUC）下的面积，分别针对10和100 mg / kg剂量组计算出低生物利用度，分别为16.4％和5.6％。 BPA在DA / Han大鼠中的毒代动力学特性与以下假设有关：肝脏快速消除首过效应，低剂量口服有效代谢清除。如果排毒途径饱和，则仅过量使用可能导致生物蓄积。

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