Thyroid disrupting chemicals: mechanisms and mixtures
Thyroid disrupting chemicals: mechanisms and mixtures
复制标题
DOI：
10.1111/j.1365-2605.2007.00857.x
复制
发表时间：
2008-04-01
影响因子：
--
通讯作者：
Crofton, Kevin M.
中科院分区：
文献类型：
--
作者：
Crofton, Kevin M.
众所周知，环境污染物会破坏甲状腺的化学物质（TDC）。广义上讲，TDC 是一种异生素，可以改变甲状腺的结构或功能、改变与甲状腺激素 (TH) 稳态相关的调节酶或改变 TH 的循环或组织浓度。对于 TH，稳态被定义为循环和组织中 TH 和 TSH 的正常范围。 TDC 包含多种化学结构，可通过多种机制发挥作用。由于甲状腺激素在大脑发育中发挥着关键作用，人们对 TDC 的担忧有所增加。关于环境外源性物质内分泌干扰潜力的一个主要不确定性是接触混合物后可能产生相加、拮抗或协同作用。此外，TDC 混合物研究结果的解释和外推都存在许多不确定性。将实验动物的数据外推到人类会受到物种间 TDC 作用机制差异的不确定性的影响。 TDC 改变甲状腺稳态的机制多种多样，这也给确定在什么水平的生物组织上累积效应带来了困难。它应该在分子水平上（可能是特定于化学类别的）还是在下游结果水平上（例如循环激素水平、大脑生物化学和行为），这将是独立于机制的？迄今为止，TDC 混合物研究的有限数据表明，剂量添加在预测对血清 T4 浓度的影响方面相当准确。评估环境异生素对甲状腺破坏的健康风险需要更好地了解不同机制如何改变 TH 以及随之而来的对神经系统发育的不利影响。
Environmental contaminants are known to act as thyroid disrupting chemicals (TDCs). Broadly defined, TDCs are xenobiotics that alter the structure or function of the thyroid gland, alter regulatory enzymes associated with thyroid hormone (TH) homeostasis or change circulating or tissue concentrations of THs. For THs, homeostasis is defined as the normal range of THs and TSH in circulation and tissues. TDCs include a wide range chemical structures that act through a variety of mechanisms. Concern about TDCs has increased because of the critical role that thyroid hormones play in brain development. A major uncertainty regarding the endocrine disrupting potential of environmental xenobiotics is the potential for additive, antagonistic or synergistic effects following exposure to mixtures. In addition, there are a number of uncertainties in both interpretation and extrapolation of results from studies of TDC mixtures. Extrapolation of data from laboratory animals to humans is tempered by uncertainty in how the mechanism(s)-of-action of the TDCs may differ between species. The variety of mechanisms by which TDCs alter thyroid homeostasis also yields a difficulty in determining at what level of biological organization to cumulate effects. Should it be at the molecular level, which could be chemical class specific or at the level of a downstream consequence (e.g. circulating hormone levels, brain biochemistry and behaviour) which would be mechanism-independent? To date, the limited data from TDC mixture studies suggest that dose addition is reasonably accurate in predicting the effects on serum T4 concentrations. Assessing the health risks of thyroid disruption by environmental xenobiotics will need to include an improved understanding of how divergent mechanisms alter THs and consequent adverse impacts on nervous system development.