Characterization of liver toxicity in F344/N rats and B6C3F1 mice after exposure to a flame retardant containing lower molecular weight polybrominated diphenyl ethers.
Characterization of liver toxicity in F344/N rats and B6C3F1 mice after exposure to a flame retardant containing lower molecular weight polybrominated diphenyl ethers.
复制标题
DOI：
10.1016/j.etp.2008.06.008
复制
发表时间：
2009-01
期刊：
影响因子：
--
通讯作者：
Nyska A
中科院分区：
文献类型：
--
作者：
Dunnick JK;Nyska A
低分子量多溴二苯醚 (PBDE) 是阻燃剂的成分，存在于环境以及人类和动物组织中。在 F344/N 大鼠和 B6C3F1 小鼠中进行毒性研究，通过口服管饲法施用含有这些较低分子量 PBDE（BDE-47、BDE-99、BDE-100 和 BDE153）的阻燃剂，持续 13 周，剂量为 0.01、5、50、100 或 500 mg/kg/天。肝脏是大鼠和小鼠的主要靶器官。在大鼠和小鼠中均观察到与治疗相关的肝脏重量、肝细胞色素 P450（1A1、1A2、2B）和 UDPGT（仅限大鼠）水平以及肝脏损伤的增加。治疗后肝细胞肥大和空泡化的发生率和严重程度增加，大鼠中肝细胞肥大和空泡化的发生率在 50 mg/kg 及以上，小鼠中肝细胞肥大和空泡化的发生率在 100 mg/kg 及以上。大鼠和小鼠的肝脏 Cyp 1A1、1A2 和 2B 水平在暴露水平为 50 mg/kg 及以上时增加。此外，与治疗相关的甲状腺病变尤其发生在大鼠身上。 PBDE 毒性最敏感的参数是肝脏重量的增加，大鼠肝脏重量增加 5 mg/kg，小鼠肝脏重量增加 50 mg/kg 或以上。这些结果表明，长期施用 PBDEs 后，肝脏可能是致癌过程的靶器官。国家毒理学计划目前正在进行一项长期 PBDE 研究。
Lower molecular weight polybrominated diphenylethers (PBDEs), components of flame retardants, are found in the environment and in human and animal tissues. Toxicity studies were conducted in F344/N rats and B6C3F1 mice by administering a flame retardant containing these lower molecular weight PBDEs (BDE-47, BDE-99, BDE-100, and BDE153) by oral gavage 5 days/week for 13 weeks at doses of 0.01, 5, 50, 100 or 500 mg/kg/day. Liver was the primary target organ in rats and mice. Treatment-related increases in liver weights, liver cytochrome P450 (1A1, 1A2, 2B) and UDPGT (rats only) levels, and liver lesions were seen in both rats and mice. Hepatocyte hypertrophy and vacuolization increased in incidence and severity with treatment, and occurred at levels of 50 mg/kg and above in rats, and at 100 mg/kg and above in mice. Liver Cyp 1A1, 1A2, and 2B levels were increased at exposure levels of 50 mg/kg and above in rats and mice. In addition, treatment-related thyroid lesions occurred particularly in rats. The most sensitive parameter for PBDE toxicity was the increase in liver weights which occurred at 5 mg/kg above in rats and 50 mg/kg and above in mice. These results suggest that liver may be a target organ for carcinogenesis processes after long-term administration of PBDEs. A chronic PBDE study is currently being conducted by the National Toxicology Program.
登录
查看更多内容
影响因子：
4.3
作者：
Amacher, DE;Schomaker, SJ;Burkhardt, JE
通讯作者：
Burkhardt, JE
影响因子：
5.8
作者：
Hamm, JT;Ross, DG;Birnbaum, LS
通讯作者：
Birnbaum, LS
影响因子：
11.8
作者：
Legler, J;Brouwer, A
通讯作者：
Brouwer, A
影响因子：
8.8
作者：
Darnerud, Per Ola;Aune, Marie;Hallgren, Sara
通讯作者：
Hallgren, Sara
影响因子：
11.8
作者：
Hale, RC;Alaee, M;Ikonomou, MG
通讯作者：
Ikonomou, MG