van Birgelen A P, Hébert C D, Wenk M L, Grimes L K, Chapin R E, Mahler J, Travlos G S, Bucher J R
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA.
Toxicol Appl Pharmacol. 1999 Apr 15;156(2):147-59. doi: 10.1006/taap.1999.8640.
The toxicity of 3,3',4,4'-tetrachloroazobenzene (TCAB) was evaluated in 13-week gavage studies in male and female F344/N rats and B6C3F1 mice. In addition to histopathology, evaluations included clinical chemistry, hematology, thyroid hormone analyses, and reproductive parameters. Groups of 10 rats and 10 mice of each sex were exposed to TCAB at dose levels of 0, 0.1, 1, 3, 10, or 30 mg/kg for 5 days a week for 13 weeks. In the rat studies, the major effects for both males and females included a 10% decrease in terminal body weight at 30 mg/kg/day, an increase in hematopoietic cell proliferation in the spleen at 10 and 30 mg/kg/day, and a responsive anemia at 10 and 30 mg/kg/day. A 15 to 30% decrease in platelet counts and a 20 to 40% decrease in thymus weights was observed at 10 and 30 mg/kg/day. An increase in liver weight up to 15% was found at 3 mg/kg/day and higher doses in males and at 10 and 30 mg/kg/day in females, respectively. An increase in spleen weights up to 15% was observed at 10 and 30 mg/kg/day in males and at 30 mg/kg/day in females. A marked decrease in circulating total thyroxine (TT4) was found in both males and females at all dose levels tested. TT4 could hardly be detected at 10 and 30 mg TCAB/kg/day. In addition, hyperplasia of the forestomach was increased at 3 mg/kg/day and higher doses in males and at 30 mg/kg/day in females. In the mouse studies, an increase in liver and spleen weight was observed up to approximately 25% in both males and females at 10 and 30 mg/kg/day. Hyperplasia of the forestomach was observed at 1 mg/kg/day and higher doses in both males and females. In males, a 30% decrease in thymus weights at 30 mg/kg/day and a 60% decrease in epididymal sperm density at 3 and 30 mg/kg/day was observed. Also in males, centrilobular hypertrophy of hepatocytes and an increase in hematopoietic cell proliferation in the spleen was observed at 3 mg/kg/day and higher doses. Based on the current study and information in the literature, TCAB has dioxin-like properties. Comparison of the effects of TCAB in the present study and in the literature to those with 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) indicates that TCAB is from two to six orders of magnitude less potent than TCDD depending on the end point.
在对雄性和雌性F344/N大鼠以及B6C3F1小鼠进行的为期13周的灌胃研究中，评估了3,3',4,4'-四氯偶氮苯（TCAB）的毒性。除了组织病理学评估外，还包括临床化学、血液学、甲状腺激素分析以及生殖参数评估。每组10只雄性和10只雌性大鼠及小鼠，每周5天、持续13周暴露于剂量为0、0.1、1、3、10或30 mg/kg的TCAB。在大鼠研究中，雄性和雌性的主要影响包括：30 mg/kg/天剂量下终末体重下降10%；10和30 mg/kg/天剂量下脾脏造血细胞增殖增加；10和30 mg/kg/天剂量下出现反应性贫血。10和30 mg/kg/天剂量下，血小板计数下降15%至30%，胸腺重量下降20%至40%。雄性3 mg/kg/天及更高剂量、雌性10和30 mg/kg/天剂量下肝脏重量增加高达15%。雄性10和30 mg/kg/天、雌性30 mg/kg/天剂量下脾脏重量增加高达15%。在所有测试剂量水平下，雄性和雌性的循环总甲状腺素（TT4）均显著下降。在10和30 mg TCAB/kg/天剂量下几乎检测不到TT4。此外，雄性3 mg/kg/天及更高剂量、雌性30 mg/kg/天剂量下前胃增生增加。在小鼠研究中，10和30 mg/kg/天剂量下雄性和雌性的肝脏和脾脏重量均增加约25%。雄性和雌性在1 mg/kg/天及更高剂量下均观察到前胃增生。在雄性中，30 mg/kg/天剂量下胸腺重量下降30%，3和30 mg/kg/天剂量下附睾精子密度下降60%。同样在雄性中，3 mg/kg/天及更高剂量下观察到肝细胞中央小叶肥大和脾脏造血细胞增殖增加。基于当前研究及文献信息，TCAB具有二噁英样特性。将本研究及文献中TCAB的影响与2,3,7,8-四氯二苯并对二噁英（TCDD）的影响进行比较表明，根据终点不同，TCAB的效力比TCDD低两到六个数量级。
