Chu I, Villeneuve D C, Yagminas A, LeCavalier P, Poon R, Feeley M, Kennedy S W, Seegal R F, Häkansson H, Ahlborg U G
Environmental Health Directorate and Food Directorate, Health Protection Branch, Ottawa, Ontario, Canada.
Fundam Appl Toxicol. 1994 Apr;22(3):457-68. doi: 10.1006/faat.1994.1051.
The systemic toxicity of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) following subchronic dietary exposure was investigated in Sprague-Dawley rats. PCB 126 was administered to rats of both sexes at concentrations of 0.1, 1.0, 10, or 100 ppb in their diet for 13 weeks. Another group of rats received a loading dose of 5 micrograms PCB/kg body wt at the start of the feeding period followed by exposure to 10 ppb PCB diet for the same period of time as the other groups. Growth suppression and decreased food consumption were observed in the highest dose groups of both sexes. Increased organ/body weight ratios for the liver occurred in the 10 and 100 ppb groups of both sexes. Rats of both sexes exposed to the highest dose of the PCB also exhibited increased relative kidney, spleen, and brain weights. Hematological and most serum biochemical changes were confined to the 100 ppb groups. These included elevated alkaline phosphatase, bilirubin, cholesterol, and aspartate aminotransferase, and decreased serum glucose, hemoglobin, erythrocytes, hematocrit, and platelets. A dose-dependent increase in liver ethoxyresorufin-O-deethylase activity was observed in rats of both sexes starting at 0.1 ppb. A dose-dependent increase in liver uroporphyrin levels was observed in both sexes and significant changes occurred in the female rats at 1.0 ppb and higher dose groups. Decreased liver vitamin A was observed in the 10 ppb group and higher in both sexes. Kidney vitamin A was elevated in the 100 ppb group. No statistically significant changes were noted in concentrations of brain biogenic amines. PCB 126 residues were 10-fold higher in liver than in fat. Treatment-related histopathological changes were observed in the thymus, thyroid, bone marrow, and liver of rats exposed to the 10 ppb diet, but increased frequency of mild changes was observed in most of these tissues at the 1.0 ppb level. Based on the above data, the no adverse effect level was judged to be 0.1 ppb in the diet or 0.01 micrograms/kg body wt/day.
在斯普拉格-道利大鼠中研究了亚慢性饮食暴露后3,3',4,4',5-五氯联苯（PCB 126）的全身毒性。以0.1、1.0、10或100 ppb的浓度将PCB 126添加到雌雄大鼠的饮食中，持续13周。另一组大鼠在喂养期开始时接受5微克PCB/千克体重的负荷剂量，随后在与其他组相同的时间段内暴露于10 ppb的PCB饮食中。在雌雄大鼠的最高剂量组中均观察到生长抑制和食物摄入量减少。在雌雄大鼠的10和100 ppb组中，肝脏的器官/体重比增加。暴露于最高剂量PCB的雌雄大鼠还表现出肾脏、脾脏和大脑的相对重量增加。血液学和大多数血清生化变化仅限于100 ppb组。这些变化包括碱性磷酸酶、胆红素、胆固醇和天冬氨酸转氨酶升高，以及血清葡萄糖、血红蛋白、红细胞、血细胞比容和血小板减少。从0.1 ppb开始，在雌雄大鼠中均观察到肝脏乙氧基异吩唑酮-O-脱乙基酶活性呈剂量依赖性增加。在雌雄大鼠中均观察到肝脏尿卟啉水平呈剂量依赖性增加，在1.0 ppb及更高剂量组的雌性大鼠中发生了显著变化。在10 ppb组及以上的雌雄大鼠中均观察到肝脏维生素A减少。在100 ppb组中，肾脏维生素A升高。在脑生物胺浓度方面未观察到统计学上的显著变化。肝脏中的PCB 126残留量比脂肪中的高10倍。在暴露于10 ppb饮食的大鼠的胸腺、甲状腺、骨髓和肝脏中观察到与治疗相关的组织病理学变化，但在1.0 ppb水平时，在这些组织中的大多数中观察到轻度变化的频率增加。根据上述数据，判断饮食中无不良影响水平为0.1 ppb或0.01微克/千克体重/天。
