Zhou T, Ross D G, DeVito M J, Crofton K M
Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina, USA.
Toxicol Sci. 2001 May;61(1):76-82. doi: 10.1093/toxsci/61.1.76.
Polybrominated diphenyl ethers (PBDEs), used as flame retardants, are ubiquitous environmental contaminants. PBDEs act as endocrine disruptors via alterations in thyroid hormone homeostasis. We examined thyroid hormone concentrations and hepatic enzyme activity in weanling rats exposed to three commercial PBDE mixtures: DE-71, DE-79, and DE-83R. Female Long-Evans rats, 28 days old, were orally administered various doses of DE-71, DE-79, or DE-83R for 4 days. Serum and liver samples were collected 24 h after the last dose and analyzed for serum total thyroxine (T(4)), triiodothyronine (T(3)), thyroid-stimulating hormone (TSH), hepatic microsomal ethoxy- and pentoxy-resorufin-O-deethylase (EROD and PROD), and uridinediphosphate-glucuronosyltransferase (UDPGT) activities. The PBDE-treated groups did not exhibit significant changes in body weight; however, increased liver weights, as well as 10- to 20-fold induction in EROD and 30- to 40-fold induction in PROD were found in the DE-71-- and DE-79--treated animals. DE-71 and DE-79 caused dose-dependent depletion of T(4), accompanied by up to 3- to 4-fold induction in UDPGT activities. Serum total T(4) was decreased a maximum of 80% for DE-71 and 70% for DE-79 in the highest dose, with benchmark doses (BMDs) of approximately 12.74 mg/kg/day for DE-71 and 9.25 mg/kg/day for DE-79. Dose-related effects in serum T(3) levels were less apparent, with maximal reductions of 25-30% at the highest dose for both DE-71 and DE-79. The two mixtures showed no effect on serum TSH levels. Benchmark dose analysis revealed that the two mixtures were comparable in altering thyroid hormone levels and hepatic enzyme activity. DE-83R was not effective in altering any of the measured parameters. The present study suggests that short-term exposure to some commercial PBDE mixtures interferes with the thyroid hormone system via upregulation of UDPGTS:
多溴二苯醚（PBDEs）作为阻燃剂，是普遍存在的环境污染物。PBDEs通过改变甲状腺激素稳态而发挥内分泌干扰物的作用。我们检测了暴露于三种商用PBDE混合物（DE - 71、DE - 79和DE - 83R）的断奶大鼠的甲状腺激素浓度和肝酶活性。28日龄的雌性Long - Evans大鼠经口给予不同剂量的DE - 71、DE - 79或DE - 83R，持续4天。在末次给药后24小时采集血清和肝脏样本，分析血清总甲状腺素（T(4)）、三碘甲状腺原氨酸（T(3)）、促甲状腺激素（TSH）、肝微粒体乙氧基和戊氧基 - 间苯二酚 - O - 脱乙基酶（EROD和PROD）以及尿苷二磷酸 - 葡萄糖醛酸基转移酶（UDPGT）活性。PBDE处理组的体重未出现显著变化；然而，在DE - 71和DE - 79处理的动物中发现肝脏重量增加，EROD诱导10至20倍，PROD诱导30至40倍。DE - 71和DE - 79导致T(4)呈剂量依赖性减少，同时UDPGT活性诱导高达3至4倍。在最高剂量下，DE - 71使血清总T(4)最多降低80%，DE - 79降低70%，DE - 71的基准剂量（BMDs）约为12.74 mg/kg/天，DE - 79为9.25 mg/kg/天。血清T(3)水平的剂量相关效应不太明显，在最高剂量下，DE - 71和DE - 79的最大降幅均为25 - 30%。这两种混合物对血清TSH水平无影响。基准剂量分析表明，这两种混合物在改变甲状腺激素水平和肝酶活性方面具有可比性。DE - 83R在改变任何测量参数方面均无效。本研究表明，短期暴露于某些商用PBDE混合物会通过上调UDPGTS干扰甲状腺激素系统。
