Lai David Y, Kacew Sam, Dekant Wolfgang
Office of Chemical Safety and Pollution Prevention, Risk Assessment Division, U.S. Environment Protection Agency, Washington, DC, USA.
McLauglin Centre for Population Health Risk Assessment, University of Ottawa, Canada.
Food Chem Toxicol. 2015 Jun;80:206-214. doi: 10.1016/j.fct.2015.03.023. Epub 2015 Mar 25.
Due to potential consumer exposures, the toxicity of tetrabromobisphenol A (TBBPA) has been extensively studied. Reviews of TBBPA concluded no concerns regarding human health risks. The low toxicity of TBBPA is consistent with low bioavailability. However, some oral toxicity studies in rodents with TBBPA reported changes in thyroid hormone levels and a carcinogenicity study with TBBPA showed increased incidences of uterine tumors in rats. This review analyzes several modes of action (MoA) that may account for the observed thyroxine hormone changes and the uterine tumors. It concludes that the potential modes of action for thyroid changes induced by TBBPA are expected to exhibit a threshold for adverse effects due to the ability of the mammalian organism to compensate small changes in thyroid hormone levels. Regarding MoAs for the uterine tumors, TBBPA does not exert genotoxic or estrogenic effects. Available evidence suggests that TBBPA may increase levels of circulating estrogens by a competitive inhibition of estrogen conjugation and produce uterine tumors by promoting pre-existing Tp53-mutations due to increased estrogen levels resulting in increased cell proliferation.
由于存在潜在的消费者接触风险，四溴双酚A（TBBPA）的毒性已得到广泛研究。对TBBPA的综述得出结论，认为其对人类健康风险无担忧。TBBPA的低毒性与其低生物利用度一致。然而，一些对啮齿动物进行的TBBPA口服毒性研究报告了甲状腺激素水平的变化，并且一项TBBPA致癌性研究显示大鼠子宫肿瘤的发生率增加。本综述分析了几种可能解释所观察到的甲状腺激素变化和子宫肿瘤的作用模式（MoA）。结论是，由于哺乳动物机体能够补偿甲状腺激素水平的微小变化，TBBPA诱导甲状腺变化的潜在作用模式预计会表现出不良反应阈值。关于子宫肿瘤的作用模式，TBBPA不产生基因毒性或雌激素效应。现有证据表明，TBBPA可能通过竞争性抑制雌激素结合来增加循环雌激素水平，并由于雌激素水平升高导致细胞增殖增加，通过促进预先存在的Tp53突变而产生子宫肿瘤。
