Inter-laboratory validation study of an in vitro glucocorticoid receptor transactivation assay for testing potential endocrine disrupting chemicals

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro Pub Date : 2025-07-17 DOI:10.1016/j.tiv.2025.106109

Andrea Rivero-Arze , Marina Grimaldi , Géraldine Maillet , Cindie Gesbert , Erwan Michelin , Clémentine Garoche , Emmanuelle Maillot-Maréchal , Olivier Palluel , François Sermier , Sebastian Hoffmann , Jérôme Couteau , Philippe Hubert , Elise Grignard , Selim Aït-Aïssa , Patrick Balaguer , Torben Österlund

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引用次数: 0

Abstract

The glucocorticoid receptor (GR) belongs to the family of steroid receptors (SRs). These receptors regulate a vast selection of cell-, tissue-, and organism biology, and are also targets of endocrine disrupting chemicals warranting design and validation of in vitro assays. Here we report a “blinded” ring trial of an in vitro cell-based GR transactivation assay with four involved laboratories. The laboratories set up the assay and tested 34 selected chemicals with remarkably good concordance. There was agreement between all laboratories for the classification of activity in 97 % of the cases, and three or more laboratories were always in agreement. The within laboratory concordance was very high (99.6 %) with only one of all 272 triplicates deviating. The assay was, thus, deemed easily transferable and reproducible within and between laboratories, since they would arrive at the same qualitative results. Furthermore, for the chemicals with solid data regarding GR activation or inhibition, the laboratories arrived at the expected conclusion in all cases. Overall, the transfer and validation were successful, and the method is under evaluation to become an OECD test guideline. The method is expected to become valuable in tiered approaches for assessing chemicals or environmental samples together with other similar methods.

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用于检测潜在内分泌干扰物的体外糖皮质激素受体反激活试验的实验室间验证研究。

糖皮质激素受体（GR）属于类固醇受体（SRs）家族。这些受体调节着大量的细胞、组织和有机体生物学，也是内分泌干扰化学物质的目标，需要设计和验证体外试验。在这里，我们报告了一个“盲法”环试验的体外细胞为基础的GR转激活测定与四个相关实验室。实验室建立了测定法，并对34种选定的化学物质进行了测试，一致性非常好。在97% %的病例中，所有实验室对活动性的分类是一致的，三个或更多的实验室总是一致的。实验室内一致性非常高（99.6 %），272个三重复中只有一个偏离。因此，该分析被认为易于在实验室内部和实验室之间转移和重复，因为它们会得到相同的定性结果。此外，对于具有关于GR激活或抑制的可靠数据的化学品，实验室在所有情况下都得出了预期的结论。总的来说，转移和验证是成功的，该方法正在评估中，以成为经合组织的测试指南。该方法有望与其他类似方法一起在评估化学品或环境样品的分层方法中变得有价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.