a Division of Biochemical Toxicology , National Center for Toxicological Research, US Food and Drug Administration , Jefferson , AR , USA.
Crit Rev Toxicol. 2017 Aug;47(7):537-563. doi: 10.1080/10408444.2017.1281590. Epub 2017 Mar 6.
Exposure of the population to thiocyanate is predominantly through the diet and cigarette smoke. Thiocyanate is a potential thyroid disruptor due to its capacity to inhibit the uptake of iodide by the thyroid. Thiocyanate also interacts with the enzymatic reactions associated with iodide organification and thyroid hormone synthesis. Quantification of the dose-response relationships of thiocyanate and alteration in thyroid hormone levels is important for evaluating the risk of exposure to thiocyanate in humans. In this review, we highlight the key whole-body and intra-thyroidal aspects of thiocyanate kinetics in rats and its various modes of action for perturbing thyroid function. The inter-play between the various transporter- and enzyme-mediated modes of action contributes to the complexity in the dose-response relationship determinations for thiocyanate. We map the available modes of action in a mechanistic and quantitative manner. Findings summarized in this study can help support the development of a quantitative model to study the interaction effects of thiocyanate on the thyroid function. Additionally, the data gaps identified can help guide future experimental designs to characterize further thiocyanate dose-response. Finally, the strengths and weaknesses in current risk assessment considerations used for thiocyanate as a component of thyroid-active chemical mixtures are discussed.
人群接触硫氰酸盐主要通过饮食和吸烟。由于其抑制甲状腺摄取碘的能力，硫氰酸盐是一种潜在的甲状腺干扰物。硫氰酸盐还与碘有机化和甲状腺激素合成相关的酶反应相互作用。定量评估硫氰酸盐的剂量-反应关系和甲状腺激素水平的改变对于评估人类接触硫氰酸盐的风险非常重要。在这篇综述中，我们强调了大鼠硫氰酸盐动力学的全身和甲状腺内关键方面及其干扰甲状腺功能的各种作用模式。各种转运体和酶介导的作用模式之间的相互作用导致了硫氰酸盐剂量-反应关系确定的复杂性。我们以一种机制和定量的方式来描述现有的作用模式。本研究总结的发现可以帮助支持开发一种定量模型来研究硫氰酸盐对甲状腺功能的相互作用效应。此外，确定的数据差距可以帮助指导未来的实验设计，以进一步表征硫氰酸盐的剂量-反应。最后，讨论了当前作为甲状腺活性化学混合物成分的硫氰酸盐风险评估考虑因素的优缺点。
