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鼠和人类体外试验对甲状腺毒性评估的比较评估

Laure Asselin¹, Audrey Baze¹, Betty Ory¹

¹KaLy-Cell SAS, Plobsheim, France.

|December 2, 2024

概括

这项研究评估了使用老鼠和人类体外模型对甲状腺功能的化学影响. 结果显示,在体内影响甲状腺激素的化学物质在体内也抑制关键的甲状腺酶,支持比较安全性评估.

科学领域:

内分泌学和毒理学.
在体外毒理学.
甲状腺激素调节甲状腺激素调节

背景情况:

甲状腺激素对于发育和新陈代谢至关重要.
化学物质可以通过各种机制破坏甲状腺功能.
在体外模型对于查化学毒性至关重要.

研究的目的:

为了比较试验化学品对关键甲状腺终点在老鼠和人类体外系统中的影响.
评估体外甲状腺模型对风险评估的有用性.

主要方法:

评估了酸同载体 (NIS),甲状腺过氧化酶 (TPO) 和二氧化酶 (DIOs) I,II和III的抑制.
在实验室中利用了老鼠和人类细胞系统.
测试了十种已知或疑似对甲状腺功能的化学物质.

主要成果:

影响甲状腺激素 (TH) 水平的化学物质在体内抑制了体外测试的终点,在不同物种中类似.
化物运输阻断剂5抑制了NIS,TPO和DIO1/2,并产生了额外的ATP耗尽效应.
利芬素抑制了老鼠和人类的TPO,表明直接影响甲状腺,而其他肝脏诱导剂是无效的.

结论:

实验室老鼠和人类的NIS,TPO和DIO系统有效地预测了体内甲状腺干扰.
在体外比较数据支持基于风险的化学安全决策.
一些化学物质表现出甲状腺干扰的复杂机制,超出了直接的酶抑制.

关键词:

脱氧化的使用方法内分泌干扰干扰内分泌系统人类相关性的人类相关性新方法方法论新方法方法论酸的同载体是酸.甲状腺过氧化酶是什么

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