Evangelista Marco, Papa Ester
QSAR Research Unit in Environmental Chemistry and Ecotoxicology, Department of Theoretical and Applied Sciences, University of Insubria, Via J.H. Dunant 3, 21100 Varese, Italy.
Department of Science and High Technology, University of Insubria, Via Valleggio 11, 22100 Como, Italy.
Toxics. 2025 Sep 19;13(9):799. doi: 10.3390/toxics13090799.
Thyroid hormone (TH) system disruption by chemicals poses a significant concern due to the key role the TH system plays in essential body functions, including the metabolism, growth, and brain development. Animal-based testing methods are resource-demanding and raise ethical issues. Thus, there is a recognised need for new approach methodologies, such as quantitative structure-activity relationship (QSAR) models, to advance chemical hazard assessments. This review, covering the scientific literature from 2010 to 2024, aimed to map the current landscape of QSAR model development for predicting TH system disruption. The focus was placed on QSARs that address molecular initiating events within the adverse outcome pathway for TH system disruption. A total of thirty papers presenting eighty-six different QSARs were selected based on predefined criteria. A discussion on the endpoints and chemical classes modelled, data sources, modelling approaches, and the molecular descriptors selected, including their mechanistic interpretations, was provided. By serving as a "state-of-the-art" of the field, existing models and gaps were identified and highlighted. This review can be used to inform future research studies aimed at advancing the assessment of TH system disruption by chemicals without relying on animal-based testing, highlighting areas that require additional research.
由于甲状腺激素（TH）系统在包括新陈代谢、生长和大脑发育等基本身体功能中发挥着关键作用，化学物质对其造成的干扰引发了重大关注。基于动物的测试方法需要大量资源且引发伦理问题。因此，人们认识到需要新的方法，如定量构效关系（QSAR）模型，以推进化学物质危害评估。本综述涵盖了2010年至2024年的科学文献，旨在描绘预测TH系统干扰的QSAR模型开发的当前状况。重点放在解决TH系统干扰不良结局途径内分子引发事件的QSAR上。根据预定义标准共筛选出30篇呈现86种不同QSAR的论文。对所建模的终点和化学类别、数据来源、建模方法以及所选分子描述符（包括其机理解释）进行了讨论。作为该领域的“最新技术水平”，识别并突出了现有模型和差距。本综述可用于为未来旨在推进不依赖基于动物测试的化学物质对TH系统干扰评估的研究提供信息，突出需要进一步研究的领域。
