Toxic potency of 2,3,3',4,4',5-hexachlorobiphenyl relative to and in combination with 2,3,7,8-tetrachlorodibenzo-p-dioxin in a subchronic feeding study in the rat.
Toxic potency of 2,3,3',4,4',5-hexachlorobiphenyl relative to and in combination with 2,3,7,8-tetrachlorodibenzo-p-dioxin in a subchronic feeding study in the rat.
复制标题
在大鼠亚慢性喂养研究中，2,3,3,4,4,5-六氯联苯相对于 2,3,7,8-四氯二苯并-对二恶英及其组合的毒性效力。
DOI：
10.1006/taap.1994.1155
复制
发表时间：
1994
影响因子：
3.8
通讯作者：
M. Berg
中科院分区：
文献类型：
--
作者：
A. V. Birgelen;J. V. D. Kolk;K. Fase;I. Bol;H. Poiger;A. Brouwer;M. Berg
通过对雌性SD大鼠13周的饲养试验，研究了2，3，3 '，4，4'，5-六氯联苯（PCB 156）与2，3，7，8-四氯二苯并对二恶英（TCDD）的交互作用对毒性和生化指标的影响。饲料中添加了PCB 156（1.2、6或12毫克/千克）、TCDD（5微克/千克）或两种化合物的组合。估计每日摄入量为365微克/千克体重/天（6毫克/千克饮食组）的PCB 156导致体重增加减少、胸腺萎缩、肝脏增大、肝脏类维生素A损失、CYP 2B活性诱导和血浆甲状腺素浓度降低。估计每日摄入量为81微克PCB 156/千克体重/天时，可诱导CYP 1A 1和CYP 1A 2活性。与四氯二苯并对二恶英同时亚慢性喂养研究相比，估计多氯联苯156的毒性当量因子（TEF）在0.00004和0.001之间。发现TCDD和PCB 156对CYP 2B活性和肝脏视黄醇水平具有拮抗作用。这些影响同时与PCB 156剂量依赖性降低肝脏TCDD水平。在1.2 mg PCB 156/kg剂量组与TCDD联合给药时，发现肝脏PCB 156水平升高。总之，至少部分PCB 156和TCDD之间的拮抗作用观察到有一个毒理动力学基础。此外，与TEF值的不确定性相比，拮抗作用的大小可以忽略不计。因此，PCB 156和TCDD之间的相互作用可能对TEF概念的加和性没有影响。
Interactive effects on toxicity and biochemical parameters were studied between 2,3,3',4,4',5-hexachlorobiphenyl (PCB 156) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a 13-week feeding study of female Sprague-Dawley rats. The diets were supplemented with PCB 156 (1.2, 6, or 12 mg/kg), with TCDD (5 micrograms/kg), or with combinations of both compounds. Estimated daily intake of 365 micrograms/kg body wt/day (6 mg/kg diet group) of PCB 156 caused a decrease in body weight gain, thymic atrophy, liver enlargement, a loss in hepatic retinoids, induction of CYP2B activity, and a decrease in plasma thyroxine concentrations. At an estimated daily intake of 81 micrograms PCB 156/kg body wt/day CYP1A1 and CYP1A2 activities were induced. Compared to a simultaneous subchronic feeding study with TCDD a toxic equivalency factor (TEF) between 0.00004 and 0.001 was estimated for PCB 156 with respect to the mentioned effects. Antagonistic effects were found between TCDD and PCB 156 for CYP2B activity and hepatic retinol levels. These effects concurred with a PCB 156 dose-dependent decrease in hepatic TCDD levels. Hepatic PCB 156 levels were found to be increased at the 1.2-mg PCB 156/kg dose group in coadministration with TCDD. In conclusion, at least part of the antagonistic effects between PCB 156 and TCDD observed have a toxico-kinetic base. Furthermore, the magnitude of the antagonistic effects may be neglected in comparison with the uncertainty in the TEF value. Therefore, the interactive effects found between PCB 156 and TCDD may have no implications for the additivity of the TEF concept.