Division of Neurotoxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
Neurotoxicol Teratol. 2012 Nov-Dec;34(6):598-606. doi: 10.1016/j.ntt.2012.09.006. Epub 2012 Oct 3.
Widespread bisphenol A (BPA) exposure necessitates increased knowledge of its potential effects for better risk assessment and regulatory guidance. Here, female Sprague-Dawley rats, reared in low exogenous estrogen environments and bred at adulthood, were gavaged on gestational days 6-21 with vehicle (VEH), 2.5 or 25.0 μg/kg/day BPA, or 5.0 or 10.0 μg/kg/day ethinyl estradiol (EE₂). Offspring were orally treated on postnatal days (PNDs) 1-21 with the same dose their dam received. A naïve control group (NC) was not gavaged. Post-weaning, one offspring/sex/litter (n=11-12/sex/group) was assessed for the typical behaviors measured in developmental neurotoxicology studies. At PND 29, novelty preference was unaffected by treatment; however, relative to the VEH group, males and females of both EE₂ groups were more active. VEH males appeared somewhat hypoactive in open field assessments at PNDs 40-42 and, as a result, males of the BPA and EE₂ groups were significantly more active. Latency to locate the Barnes maze escape box at PNDs 47-50 was increased in males and females of the 5.0 μg/kg/day EE₂ group. Relative to other male groups, VEH males exhibited an increased startle response on the first trial block at PND 54 and thus, males of both BPA groups and the 10.0 μg/kg/day EE₂ group exhibited a significantly decreased startle response. PNDs 43-44 motor coordination and PNDs 75-79 water maze performance were unaffected by treatment. These results indicate few consistent or dose-related effects resulting from developmental treatment with BPA at these doses. Few of these behaviors, however, were sexually dimorphic which may prove more sensitive.
广泛的双酚 A (BPA) 暴露需要增加对其潜在影响的认识,以便更好地进行风险评估和监管指导。在这里,在低外源性雌激素环境中饲养并在成年期繁殖的雌性 Sprague-Dawley 大鼠,在妊娠第 6-21 天经口给予载体 (VEH)、2.5 或 25.0μg/kg/天 BPA 或 5.0 或 10.0μg/kg/天乙炔雌二醇 (EE₂)。后代在出生后第 1-21 天接受与其母鼠相同剂量的口服治疗。一组未经处理的对照 (NC) 组未进行灌胃。断奶后,每窝 1 只雄性/雌性/幼崽(n=11-12/性别/组)接受发育神经毒理学研究中测量的典型行为评估。在 PND 29 时,新异性偏好不受处理影响;然而,与 VEH 组相比,EE₂ 组的雄性和雌性均更活跃。VEH 雄性在 PND 40-42 时在开阔场评估中似乎有些活动减少,因此 BPA 和 EE₂ 组的雄性均更活跃。在 PND 47-50 时,5.0μg/kg/天 EE₂ 组的雄性和雌性找到 Barnes 迷宫逃脱箱的潜伏期增加。与其他雄性组相比,VEH 雄性在 PND 54 的第一试验块中表现出更大的惊跳反应,因此 BPA 两组和 10.0μg/kg/天 EE₂ 组的雄性惊跳反应显著降低。PND 43-44 运动协调和 PND 75-79 水迷宫性能不受处理影响。这些结果表明,在这些剂量下,发育过程中用 BPA 处理很少会产生一致或剂量相关的影响。然而,这些行为中很少有性别二态性,这可能更敏感。