Background and aim

Endocrine disrupting chemicals (EDCs) constitute a major public health concern because they can induce a large spectrum of adverse effects by interfering with the hormonal system. Rapid identification of potential EDCs using in vitro screenings is therefore critical, particularly for chemicals of emerging concerns such as replacement flame retardants (FRs). The review aimed at identifying (1) data gaps and research needs regarding endocrine disrupting (ED) properties of replacement FRs and (2) potential EDCs among these emerging chemicals.

Methods

A systematic search was performed from open literature and ToxCast/Tox21 programs, and results from in vitro tests on the activities of 52 replacement FRs towards five hormone nuclear receptors (NRs) associated with reproductive outcomes (estrogen, androgen, glucocorticoid, progesterone, and aryl hydrocarbon receptors) were compiled and organized into tables. Findings were complemented with information from structure-based in silico model predictions and in vivo information when relevant.

Results

For the majority of the 52 replacement FRs, experimental in vitro data on activities towards these five NRs were either incomplete (15 FRs) or not found (24 FRs). Within the replacement FRs for which effect data were found, some appeared as candidate EDCs, such as triphenyl phosphate (TPhP) and tris(1,3-dichloropropyl)phosphate (TDCIPP). The search also revealed shared ED profiles. For example, anti-androgenic activity was reported for 19 FRs and predicted for another 21 FRs.

Discussion

This comprehensive review points to critical gaps in knowledge on ED potential for many replacement FRs, including chemicals to which the general population is likely exposed. Although this review does not cover all possible characteristics of ED, it allowed the identification of potential EDCs associated with reproductive outcomes, calling for deeper evaluation and possibly future regulation of these chemicals. By identifying shared ED profiles, this work also raises concerns for mixture effects since the population is co-exposed to several FRs and other chemicals.

中文翻译：

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替代阻燃剂的内分泌干扰潜能–审查与生殖结局相关的核受体的最新知识

背景和目标

破坏内分泌的化学物质（EDC）构成了主要的公共卫生问题，因为它们可以通过干扰荷尔蒙系统而引起广泛的不利影响。因此，使用体外筛选快速识别潜在的EDC至关重要，特别是对于新兴关注的化学品，例如替代阻燃剂（FR）。该审查旨在确定（1）有关替代FRs的内分泌干扰（ED）特性的数据缺口和研究需求，以及（2）这些新兴化学品中的潜在EDCs。

方法

从公开的文献和ToxCast / Tox21程序中进行了系统的搜索，并从52个替代FRs对与生殖结果（雌激素，雄激素，糖皮质激素，孕酮和芳基）相关的五个激素核受体（NRs）的活性进行了体外测试，得出了结果。碳氢化合物受体）被整理并组织成表格。结果与基于结构的计算机模拟模型预测的信息以及相关的体内信息相辅相成。

结果

对于52个替代FR中的大多数，关于这5个NR的活性的体外实验数据要么不完整（15 FR），要么未找到（24 FR）。在发现其影响数据的替代FR中，一些作为候选EDC出现，例如磷酸三苯酯（TPhP）和磷酸三（1,3-二氯丙基）酯（TDCIPP）。搜索还显示了共享的ED配置文件。例如，据报道抗雄激素活性为19个FR，预计为另外21个FR。

讨论

这项全面审查指出，许多替代阻燃剂（包括普通人群可能接触的化学药品）在ED潜力方面的知识方面存在严重差距。尽管本次审查并未涵盖ED的所有可能特征，但它允许鉴定与生殖结果相关的潜在EDC，要求对这些化学物质进行更深入的评估并可能在将来进行监管。通过识别共享的ED谱，这项工作也引起了对混合效应的担忧，因为该人群被共同暴露于几种FR和其他化学物质中。