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首页> 外文期刊>Archives of Toxicology >Evaluation of mechanisms inducing thyroid toxicity and the ability of the enhanced OECD Test Guideline 407 to detect these changes.
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Evaluation of mechanisms inducing thyroid toxicity and the ability of the enhanced OECD Test Guideline 407 to detect these changes.

机译：评估诱发甲状腺毒性的机制以及增强的OECD测试指南407检测这些变化的能力。

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The OECD has developed an "enhanced Test Guideline 407" (TG 407) protocol for detecting endocrine effects during the course of a 28-day testing scheme. This protocol has gone through a validation process with (anti)estrogenic and (anti)androgenic compounds and substances that affect the thyroid (thyroxine and propylthiouracil). This review investigates whether a 28-day testing scheme would show up alterations in the thyroid-related parameters of the "enhanced TG 407" (T3, T4, TSH, thyroid weight and histopathology), irrespective of the mode of action. For each mode of action, a generally accepted reference chemical was selected and an in-depth literature survey was carried out, and the chemical was evaluated for treatment-related changes of thyroid-dependent parameters. The following model chemicals were selected: ion perchlorate, blockage of iodine uptake; propylthiouracil, inhibition of thyroid hormone synthesis; excess of iodine, blockage of thyroid hormone release; pyrazole, thyroid cytotoxicity; minocycline, thyroid pigmentation; amiodarone, inhibition of TSH synthesis; diethylstilbestrol, competition for thyroid hormone binding globulin; selenium-deficient diet, inhibition of thyroxine deiodination; FD&C Red No. 3, inhibition of peripheral 5'-deiodinase; cadmium, lipid peroxidation; phenobarbital, increase in thyroxine conjugation and biliary excretion; temelastine, thyroxine accumulation. Test data for treatments lasting approximately one month were available for most of these model chemicals, and these demonstrated the expected thyroid-related changes. Thus, it can be concluded that a 28-day testing scheme allows for the detection of thyroid-disrupting chemicals. The literature data also were evaluated according to whether preference can be given to any of the thyroid-related parameters (thyroid/pituitary hormones, thyroid weight and histopathology) with regard to dose-related sensitivities. Due to different study designs (such as treatment duration, application mode, dose selection and parametersused), no clear picture emerged. Therefore, consideration should be given to all of these parameters, which should also help to define the mode of action. Overall, this literature review provides support for the contention that the newly developed "enhanced TG 407" test protocol is well suited to the detection of chemicals that affect the thyroid gland.
机译：经合组织已经制定了“增强测试指南407”（TG 407）协议，用于在28天的测试计划过程中检测内分泌作用。该方案已通过涉及（抗）雌激素和（抗）雄激素化合物以及影响甲状腺的物质（甲状腺素和丙基硫尿嘧啶）的验证过程。这项审查调查28天的测试计划是否会显示“增强的TG 407”的甲状腺相关参数的改变（T3，T4，TSH，甲状腺重量和组织病理学），无论其作用方式如何。对于每种作用方式，选择一种普遍接受的参考化学药品，并进行了深入的文献调查，并对该化学药品的甲状腺相关参数与治疗相关的变化进行了评估。选择了以下模型化学品：高氯酸根离子，碘吸收阻滞;丙基硫氧嘧啶，抑制甲状腺激素合成;碘过量，阻碍甲状腺激素释放;吡唑，甲状腺细胞毒性;米诺环素，甲状腺色素沉着;胺碘酮，抑制TSH合成;己烯雌酚，竞争甲状腺激素结合球蛋白;缺硒饮食，抑制甲状腺素碘化作用; FD＆C红色3号，抑制外周5'-脱碘酶;镉，脂质过氧化;苯巴比妥，甲状腺素结合增加和胆汁排泄;替米司汀，甲状腺素积聚。这些模型化学品中的大多数均可获得约一个月的治疗测试数据，这些数据证明了预期的甲状腺相关变化。因此，可以得出结论，一个为期28天的测试方案可以检测破坏甲状腺的化学物质。还根据剂量相关的敏感性，是否可以优先考虑任何与甲状腺有关的参数（甲状腺/垂体激素，甲状腺重量和组织病理学）来评估文献数据。由于不同的研究设计（例如治疗时间，应用模式，剂量选择和使用的参数），没有清晰的画面出现。因此，应考虑所有这些参数，这也应有助于定义作用方式。总的来说，该文献综述为新开发的“增强型TG 407”测试方案非常适合检测影响甲状腺的化学物质提供了支持。

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