链接转胺结合化学物质和自由甲状腺激素:以竞争性结合模型为基础的体外到体外推断
Kai Huang1,2, Wei Zhou1,2, Jie Fu1,2
1School of Environment, Hangzhou Institute for Advanced Study, UCAS, Hangzhou 310024, China.
Environmental science & technology
|June 1, 2023
概括
污染物与TTR结合可以改变甲状腺激素水平. 这项研究开发了一种方法来预测这些体内效应,显示一般人群中自由甲状腺激素的小增加和职业暴露的较大增加.
科学领域:
- 环境化学环境化学
- 毒理学 毒理学 毒理学
- 内分泌学 在内分泌学.
背景情况:
- 许多污染物在体外竞争性地抑制甲状腺激素与甲胺 (TTR) 的结合.
- 这种TTR结合对自由甲状腺激素水平的体内影响在很大程度上仍未被描述.
研究的目的:
- 建立一个量化体外到体外抽取 (QIVIVE) 方法,以预测TTR结合化学物质对人类血液中自由甲状腺激素的影响.
- 评估与25种选择的TTR结合化学物质同时暴露对循环中的自由甲状腺激素水平的体内影响.
主要方法:
- 开发了一个基于竞争性绑定模型的QIVIVE模型.
- 使用了体外结合参数和人类暴露数据.
- 研究了25种TTR结合化学物质,包括OH-PDBE,OH-PCB,烯,PFAS和.
主要成果:
- QIVIVE模型成功地预测了对自由甲状腺激素的体内影响.
- 同时暴露于25种TTR结合化学物质导致一般人群中自由甲状腺素 (FT4) 的中位数增加了0.080%,自由三甲状腺素 (FT3) 的中位数增加了0.06%.
- 职业暴露导致自由甲状腺激素水平增加1.8832.2%.
结论:
- 该研究提供了一种定量工具,用于评估TTR结合化学物质对甲状腺干扰的风险.
- 提出了一个新的框架来评估化学暴露对甲状腺激素等内源分子的体内影响.
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