St Omer V E, Mohammad F K
Laboratory of Neurobehavioral Toxicology and Neuropharmacology, Sinclair Research Farm, Columbia, MO 65211.
Neuropharmacology. 1987 Sep;26(9):1351-8. doi: 10.1016/0028-3908(87)90098-0.
Rats exposed in utero on gestational days 6-15, to nonfetotoxic and grossly nonteratogenic mixtures (50 or 100 mg/kg) of 2,4-D/2,4,5-T as found in Agent Orange (but without significant contamination with 2,3,7,8 tetrachloro-p-dioxin) manifested subtle developmental neurotoxicity. Maturation of swimming behavior was significantly delayed on postnatal day 7 in both treatment groups. The concentration of norepinephrine (NE) in whole brain was significantly increased on postnatal day 15 in both treatment groups, whereas the concentration of dopamine (DA) was increased on postnatal day 15 at 100 mg/kg. The turnover and efflux rate constant of DA in whole brain were significantly reduced whereas the turnover time increased on postnatal day 3. The efflux rate constant for NE decreased and the turnover time increased significantly on postnatal day 15 at 100 mg/kg. These data indicate the value of ontogenic assessment following exposure to small doses, which result in functional alterations in the absence of overt toxic signs.
在孕期第6至15天子宫内暴露于非致畸毒性且明显无致畸性的2,4-二氯苯氧乙酸/2,4,5-涕混合物（50或100毫克/千克）（如橙剂中所含，但无2,3,7,8-四氯二苯并对二恶英的显著污染）的大鼠表现出轻微的发育性神经毒性。两个治疗组在出生后第7天游泳行为的成熟均显著延迟。两个治疗组在出生后第15天全脑中去甲肾上腺素（NE）的浓度均显著升高，而在100毫克/千克剂量下，出生后第15天多巴胺（DA）的浓度升高。出生后第3天，全脑中DA的周转率和流出速率常数显著降低，而周转时间增加。在100毫克/千克剂量下，出生后第15天NE的流出速率常数降低，周转时间显著增加。这些数据表明了在暴露于小剂量后进行个体发育评估的价值，这些小剂量会在无明显毒性迹象的情况下导致功能改变。
