Department of Food Safety and Veterinary Public Health, Istituto Superiore di Sanità, Rome, Italy.
Food Chem Toxicol. 2013 Sep;59:261-71. doi: 10.1016/j.fct.2013.05.048. Epub 2013 Jun 15.
Ethylenethiourea (ETU) is the common metabolite of the widely used ethylenebisdithiocarbamate fungicides. It is identified as Endocrine Disruptor given its ability to interfere with thyroid hormone biosynthesis by inhibiting thyroid peroxidase activity. As far as we know, no studies have been performed to assess potential effects of ETU exposure at low dose levels, i.e. below the established LOAEL and NOAEL, during critical phases of development. Therefore, the aim of the present study was to verify the short- and long-term effects on thyroid function, reproduction and development of oral exposure to ETU levels comparable to and lower than LOAEL/NOAEL in rats. Sixty dams were treated daily by gavage during pregnancy and lactation with 0, 0.1, 0.3, 1.0 mg/kg bw per day of ETU. F1 generation was similarly treated from weaning to sexual maturity. Thyroid biomarkers were analyzed in dams and in offspring. Reproductive biomarkers were analyzed in F1 rats. For the first time this study has demonstrated reproductive toxicity and hypothyroidism at a lower than LOAEL dose exposure in pregnant dams and F1 generation. Our data suggest that even low doses of ETU can interfere with thyroid homeostasis and reproductive hormone profile if exposure starts in critical stages of development.
乙撑硫脲（ETU）是广泛使用的乙撑双二硫代氨基甲酸酯类杀菌剂的常见代谢物。由于其能够通过抑制甲状腺过氧化物酶活性来干扰甲状腺激素的生物合成，因此被确定为内分泌干扰物。据我们所知，尚未进行研究评估在发育关键阶段以低于已建立的 LOAEL 和 NOAEL 的低剂量水平（即低于 LOAEL/NOAEL）暴露于 ETU 时的潜在影响。因此，本研究的目的是验证口服 ETU 水平对甲状腺功能、生殖和发育的短期和长期影响，这些水平与大鼠中的 LOAEL/NOAEL 相当或低于 LOAEL/NOAEL。60 只孕鼠在孕期和哺乳期通过灌胃每天接受 0、0.1、0.3、1.0 mg/kg bw 的 ETU 处理。F1 代从断奶到性成熟也接受类似的处理。分析了孕鼠和后代的甲状腺生物标志物。分析了 F1 大鼠的生殖生物标志物。本研究首次证明了在低于 LOAEL 剂量暴露的孕鼠和 F1 代中存在生殖毒性和甲状腺功能减退症。我们的数据表明，即使暴露于低剂量的 ETU，如果在发育的关键阶段开始，也可能干扰甲状腺的内稳态和生殖激素谱。
