Division of Neurotoxicology, National Center for Toxicological Research/FDA, United States.
Neurotoxicol Teratol. 2010 May-Jun;32(3):373-82. doi: 10.1016/j.ntt.2010.01.010. Epub 2010 Jan 29.
At high levels of exposure, acrylamide monomer (AA) is a known neurotoxicant (LoPachin, 2004 [23]). The effects of lower levels of exposure, such as those experienced via a typical human diet, have not been widely investigated. Data at these levels are particularly relevant given the widespread human exposure through carbohydrate-containing foods cooked at high temperatures. Additionally, daily AA intake is estimated to be higher for infants and children. Earlier, we described behavioral alterations in preweaning rats resulting from developmental AA treatment (0.5-10.0mg/kg/day) (Garey et al., 2005 [14]). In the present study, the effects of lower doses were measured as well as serum AA and glycidimide (GA) levels in dams, fetuses, and young pups. Pregnant Fischer 344 dams (n=48-58/treatment group) were gavaged with 0.0, 0.1, 0.3, 1.0, or 5.0mg AA/kg/day beginning on gestational day 6 and ending on the day of parturition. Beginning on postnatal day 1 (PND 1) and continuing through PND 21, all pups/litter were gavaged with the same dose as their dam. There were no AA treatment effects on offspring fur development, pinnae detachment, or eye opening. Offspring body weight was somewhat decreased by 5.0mg/kg/day, particularly in males. However, righting reflex (PNDs 4-7), slant board (i.e., negative geotaxis) (PNDs 8-10), forelimb hang (PNDs 12-16), and rotarod behavior (PNDs 21-22) were not significantly altered by AA treatment. Male and female offspring of the 5.0mg/kg/day group were 30-49% less active in the open field at PNDs 19-20 (p<0.05). Serum AA levels of GD20 dams and their fetuses were comparable, indicating the ability of AA to cross the placental barrier. AA levels of pups were not affected by age (PND 1 and 22) or sex. In all rats, serum AA and GA levels exhibited a dose-response relationship. These data extend those of our previous study (Garey et al., 2005 [14]) and demonstrate that overt preweaning neurobehavioral effects are apparent in rats exposed to acrylamide pre- and postnatally, but only at the highest doses tested.
在高暴露水平下，丙烯酰胺单体（AA）是一种已知的神经毒物（LoPachin，2004 [23]）。在较低暴露水平下的影响，例如通过典型的人类饮食所经历的影响，尚未得到广泛研究。鉴于通过高温烹饪含碳水化合物的食物，人类广泛接触这些水平的数据特别相关。此外，婴儿和儿童的每日 AA 摄入量估计更高。早些时候，我们描述了发育性 AA 处理（0.5-10.0mg/kg/天）对孕前大鼠的行为改变（Garey 等人，2005 [14]）。在本研究中，我们还测量了较低剂量的影响，以及母体、胎儿和幼仔的血清 AA 和丙烯醛（GA）水平。从妊娠第 6 天开始至分娩结束，48-58/治疗组的怀孕 Fischer 344 母鼠（n=48-58/治疗组）经口给予 0.0、0.1、0.3、1.0 或 5.0mg AA/kg/天。从出生后第 1 天（PND 1）开始，所有幼仔/窝都以与母鼠相同的剂量经口给予。AA 处理对后代的皮毛发育、耳壳分离或眼睛张开没有影响。5.0mg/kg/天的剂量会使后代的体重略有下降，尤其是雄性。然而，翻正反射（PND 4-7）、斜板（即负趋地性）（PND 8-10）、前肢悬挂（PND 12-16）和旋转棒行为（PND 21-22）不受 AA 处理的显著影响。5.0mg/kg/天组的雄性和雌性后代在 PND 19-20 时在开阔场中活跃度降低 30-49%（p<0.05）。GD20 母鼠及其胎儿的血清 AA 水平相当，表明 AA 能够穿过胎盘屏障。幼仔的 AA 水平不受年龄（PND 1 和 22）或性别影响。在所有大鼠中，血清 AA 和 GA 水平均呈剂量反应关系。这些数据扩展了我们之前的研究（Garey 等人，2005 [14]）的结果，并表明在暴露于丙烯酰胺的产前和产后的大鼠中，明显的孕前神经行为影响，但仅在测试的最高剂量下出现。
