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通过整合基于科学的监管实践和创新方法加强对内分泌干扰物的识别:MERLON项目。

Enhanced identification of endocrine disruptors through integration of science-based regulatory practices and innovative methodologies: The MERLON Project.

作者信息

Svingen Terje, Andersson Anna-Maria, Angelova Julianna, Axelstad Marta, Bakker Julie, Baumann Lisa, Beronius Anna, Bouftas Nora, Chalmel Frederic, Christiansen Sofie, Cornil Charlotte, Damdimopoulou Pauliina, Deepika Deepika, Dollé Martijn E T, Draskau Monica Kam, Fischer Margit Bistrup, Hagen Casper P, Hessel Ellen, Holmer Marie Louise, Hughes Samantha, Jensen Genon, Johansson Hanna Katarina Lilith, Juul Anders, Kumar Vikas, Kumar Saurav, Lardenois Aurélie, Main Katharina M, Mazaud-Guittot Severine, Moe S Jannicke, Mola Gylli, Parent Anne-Simone, Pineda Rafael, Rolland Antoine, Rosenmai Anna Kjerstine, Song You, Suglia Antonio, Tena-Sempere Manuel, Wehrli Lydia, Zilliacus Johanna, van Duursen Majorie

机构信息

National Food Institute, Technical University of Denmark, Kgs. Lyngby, Region Hovedstaden, 2800, Denmark.

Department of Growth and Reproduction, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.

出版信息

Open Res Eur. 2024 Apr 12;4:68. doi: 10.12688/openreseurope.17319.1. eCollection 2024.

Abstract

The prevalence of hormone-related health issues caused by exposure to endocrine disrupting chemicals (EDCs) is a significant, and increasing, societal challenge. Declining fertility rates together with rising incidence rates of reproductive disorders and other endocrine-related diseases underscores the urgency in taking more action. Addressing the growing threat of EDCs in our environment demands robust and reliable test methods to assess a broad variety of endpoints relevant for endocrine disruption. EDCs also require effective regulatory frameworks, especially as the current move towards greater reliance on non-animal methods in chemical testing puts to test the current paradigm for EDC identification, which requires that an adverse effect is observed in an intact organism. Although great advances have been made in the field of predictive toxicology, disruption to the endocrine system and subsequent adverse health effects may prove particularly difficult to predict without traditional animal models. The MERLON project seeks to expedite progress by integrating multispecies molecular research, new approach methodologies (NAMs), human clinical epidemiology, and systems biology to furnish mechanistic insights and explore ways forward for NAM-based identification of EDCs. The focus is on sexual development and function, from foetal sex differentiation of the reproductive system through mini-puberty and puberty to sexual maturity. The project aims are geared towards closing existing knowledge gaps in understanding the effects of EDCs on human health to ultimately support effective regulation of EDCs in the European Union and beyond.

摘要

接触内分泌干扰化学物质(EDCs)所导致的与激素相关的健康问题的流行,是一项重大且日益严峻的社会挑战。生育率下降以及生殖系统疾病和其他内分泌相关疾病发病率上升,凸显了采取更多行动的紧迫性。应对环境中EDCs日益增长的威胁,需要强大且可靠的测试方法来评估与内分泌干扰相关的广泛终点。EDCs还需要有效的监管框架,特别是鉴于当前在化学测试中越来越依赖非动物方法,这对当前的EDC识别范式进行了考验,该范式要求在完整生物体中观察到不良影响。尽管预测毒理学领域已取得巨大进展,但如果没有传统动物模型,内分泌系统的干扰及随后的不良健康影响可能特别难以预测。MERLON项目旨在通过整合多物种分子研究、新方法学(NAMs)、人类临床流行病学和系统生物学来加快进展,以提供机制性见解并探索基于NAMs识别EDCs的前进方向。重点是性发育和功能,从生殖系统的胎儿性别分化到小青春期和青春期再到性成熟。该项目的目标是填补现有知识空白,以了解EDCs对人类健康的影响,最终支持欧盟及其他地区对EDCs的有效监管。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd29/11179054/e6138b856b39/openreseurope-4-18719-g0000.jpg

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