Integrative assessment of endocrine disruption: From in vitro mechanisms to species extrapolation – Highlights of the German Pharma-Tox Summit 2025

IF 5.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

Toxicology Pub Date : 2026-02-01 Epub Date: 2025-12-11 DOI:10.1016/j.tox.2025.154370

Ute Haßmann , Lisa Gölz , René Geci , Konstantinos Stefanidis , Justin Lucky Brandt , Eleanor North , Katreece Feiertag , Christel Renate Schopfer , Sigrid Amann , Stephanie Melching-Kollmuss , Robert Landsiedel

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引用次数: 0

Abstract

Endocrine-disrupting chemicals (EDCs) are a growing focus in human and environmental risk assessment, as reflected by the new EU CLP hazard classes for endocrine disruptors. Within this context, the symposium “Cross-Species Extrapolation in Endocrine Disruption Assessments” was held at the 10th German Pharm-Tox Summit (GPTS) 2025 in Hannover (March 11–13), which formed part of the 91st annual meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT). The symposium assembled diverse lines of research addressing endocrine disruption from complementary angles. Contributions ranged from advanced experimental model systems, such as refined zebrafish embryo assays for thyroid hormone disruption, to high-throughput in silico and in vitro–based kinetic modelling frameworks that support quantitative in vitro to in vivo extrapolation and AOP-informed risk assessment. Clinical and translational perspectives were added by targeted LC–MS/MS profiling of steroid conjugates as biomarkers for adrenal tumours. Further talks expanded the mechanistic toolbox for thyroid disruption, including enzyme- and protein-binding–based in vitro assays, and highlighted metabolic endocrine disruptors that act beyond the EATS (estrogen, androgen, thyroid and steroidogenesis) pathways. A regulatory-oriented analysis of thyroid-related modes of action across vertebrate taxa underscored the importance of clearly defining domains of applicability for cross-species extrapolation. At the same time, the discussions revealed critical gaps, including still limited taxonomic applicability domains, incomplete regulatory coverage beyond established endocrine pathways and limited transparency in predictive tools. Together, these contributions illustrate how integrated experimental, computational and regulatory science can advance mechanism-based, animal-reduced assessment of endocrine disruptors.

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内分泌干扰的综合评估：从体外机制到物种外推- 2025年德国制药Tox峰会的亮点。

内分泌干扰物（EDCs）在人类和环境风险评估中日益受到关注，这反映在新的欧盟CLP对内分泌干扰物的危害分类中。在此背景下，“内分泌干扰评估中的跨物种外推”研讨会在汉诺威举行的第10届德国药学- tox峰会（GPTS） 2025（3月11日至13日）上举行，该峰会是德国实验与临床药理学和毒理学学会（DGPT）第91届年会的一部分。研讨会汇集了从互补角度解决内分泌干扰的不同研究方向。贡献范围从先进的实验模型系统，如精细的斑马鱼胚胎甲状腺激素干扰分析，到高通量的基于硅和体外的动力学建模框架，支持定量的体外到体内外推和aop知情的风险评估。通过靶向LC-MS/MS分析类固醇偶联物作为肾上腺肿瘤的生物标志物，增加了临床和翻译方面的观点。进一步的讨论扩大了甲状腺干扰的机制工具箱，包括基于酶和蛋白质结合的体外分析，并强调了代谢内分泌干扰物在EATS（雌激素、雄激素、甲状腺和类固醇）途径之外的作用。对脊椎动物类群中甲状腺相关作用模式的一项以监管为导向的分析强调了明确界定跨物种外推适用范围的重要性。与此同时，讨论也揭示了关键的差距，包括仍然有限的分类学适用领域，在已建立的内分泌途径之外的不完整的监管覆盖以及预测工具的有限透明度。总之，这些贡献说明了综合实验、计算和调控科学如何推进基于机制的、动物减少的内分泌干扰物评估。

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 医学-毒理学

CiteScore

7.80

自引率

4.40%

发文量

222

审稿时长

23 days

期刊介绍： Toxicology is an international, peer-reviewed journal that publishes only the highest quality original scientific research and critical reviews describing hypothesis-based investigations into mechanisms of toxicity associated with exposures to xenobiotic chemicals, particularly as it relates to human health. In this respect "mechanisms" is defined on both the macro (e.g. physiological, biological, kinetic, species, sex, etc.) and molecular (genomic, transcriptomic, metabolic, etc.) scale. Emphasis is placed on findings that identify novel hazards and that can be extrapolated to exposures and mechanisms that are relevant to estimating human risk. Toxicology also publishes brief communications, personal commentaries and opinion articles, as well as concise expert reviews on contemporary topics. All research and review articles published in Toxicology are subject to rigorous peer review. Authors are asked to contact the Editor-in-Chief prior to submitting review articles or commentaries for consideration for publication in Toxicology.