Chu I, Poon R, Yagminas A, Lecavalier P, Håkansson H, Valli V E, Kennedy S W, Bergman A, Seegal R F, Feeley M
Health Protection Branch, Tunney's Pasture, Ottawa, Ontario, Canada.
J Appl Toxicol. 1998 Jul-Aug;18(4):285-92. doi: 10.1002/(sici)1099-1263(199807/08)18:4<285::aid-jat510>3.0.co;2-9.
The toxicity of 2,3,3',4,4'-pentachlorobiphenyl (PCB 105) was investigated in Sprague-Dawley rats following dietary exposure to this substance at levels of 0, 0.05, 0.5, 5 or 50 ppm for 13 weeks. Growth rate and food consumption were not affected and no clinical signs of toxicity were observed. Increased incidences of enlarged, fatty liver and decreased thymic weight were observed in the highest-dose groups of both genders; these groups also had elevated hepatic microsomal ethoxyresorufin deethylase activity and uroporphyrin. Significant increases in serum cholesterol and hepatic pentoxyresorufin dealkylase activity were observed in the highest-dose males and two highest-dose females. By contrast, liver UDP-glucuronosyl transferase activity was elevated in the two highest-dose males and the highest-dose females. Urinary ascorbic acid excretion was increased in the highest-dose males. While the amount of vitamin A was decreased dose-dependently, starting at 0.5 ppm in the liver of both sexes and in the lung of the females, the level in the kidney of the highest-dose group was increased. Administration of PCB 105 resulted in decreased dopamine in the caudate nucleus region of the brain in males and homovanillic acid in caudate nucleus and nucleus accumbens of females. Increased 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were observed in the substantia nigra region of both sexes, with most of the increases being seen in highest-dose females. Anemia, characterized by decreased hemoglobin, hematocrit and red cell indices, occurred in the highest-dose group, as did eosinophilia. Treatment with PCB 105 caused dose-dependent histopathological changes in the liver and thyroid. Thymic changes were observed in the highest-dose males and two highest-dose females. Tissue residue data showed a dose-dependent accumulation of this congener in fat, liver and spleen, kidney and brain. Based on these data the no-observable-effect level of PCB 105 was judged to be 0.05 ppm or 3.9 microg kg(-1) body wt. day(-1) in males and 4.2 microg kg(-1) body wt. day(-1) in females.
在13周的时间里，以0、0.05、0.5、5或50 ppm的剂量通过饮食让斯普拉格-道利大鼠接触2,3,3',4,4'-五氯联苯（PCB 105），对其毒性进行了研究。生长速率和食物摄入量未受影响，也未观察到毒性的临床体征。在两个性别的最高剂量组中，均观察到肝脏肿大、脂肪肝发生率增加以及胸腺重量减轻；这些组的肝微粒体乙氧基试卤灵脱乙基酶活性和尿卟啉也有所升高。在最高剂量的雄性大鼠以及两个最高剂量的雌性大鼠中，血清胆固醇和肝戊氧基试卤灵脱烷基酶活性显著增加。相比之下，在两个最高剂量的雄性大鼠和最高剂量的雌性大鼠中，肝脏UDP-葡萄糖醛酸基转移酶活性升高。最高剂量的雄性大鼠尿中抗坏血酸排泄增加。虽然维生素A的量呈剂量依赖性减少，在两性肝脏中从0.5 ppm开始，雌性大鼠肺中也是如此，但最高剂量组大鼠肾脏中的维生素A水平却有所升高。给予PCB 105导致雄性大鼠脑尾状核区域多巴胺减少，雌性大鼠尾状核和伏隔核中高香草酸减少。在两性的黑质区域均观察到5-羟色胺和5-羟吲哚乙酸增加，其中大部分增加出现在最高剂量的雌性大鼠中。最高剂量组出现了以血红蛋白、血细胞比容和红细胞指数降低为特征的贫血以及嗜酸性粒细胞增多。用PCB 105处理导致肝脏和甲状腺出现剂量依赖性组织病理学变化。在最高剂量的雄性大鼠和两个最高剂量的雌性大鼠中观察到胸腺变化。组织残留数据表明该同系物在脂肪、肝脏、脾脏、肾脏和大脑中呈剂量依赖性蓄积。基于这些数据，PCB 105的无可见效应水平在雄性大鼠中判定为0.05 ppm或3.9微克/千克体重·天，在雌性大鼠中为4.2微克/千克体重·天。
