Identification of new PFAS for severe interference with thyroid hormone transport: a combined in vitro/silico approach

IF 12.2 1区 环境科学与生态学 Q1 ENGINEERING, ENVIRONMENTAL Journal of Hazardous Materials Pub Date : 2025-03-17 DOI:10.1016/j.jhazmat.2025.137949
Anita Sosnowska, Michalina Mudlaff, Enrico Mombelli, Peter Behnisch, Szymon Zdybel, Harrie Besselink, Jochen Kuckelkorn, Natalia Bulawska, Kacper Kepka, Dominika Kowalska, Abraham Brouwer, Tomasz Puzyn
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Abstract

A tiered in vitro/in silico approach was developed to screen 12,654 per- and polyfluoroalkyl substances (PFAS) for their potential to disrupt the thyroid hormone transport. Initially, a set of 45 PFAS was tested using TTR-TRβ-CALUX bioassay, which was subsequently employed to develop a classification model, distinguishing active and inactive PFAS. The model fulfills all good practices for QSAR model validation and can predict whether a given PFAS can disrupt plasma transport of the thyroid hormone (T4). Subsequently, active compounds were used to develop two regression approaches: (i) multiple linear regression MLR, and (ii) second approach aimed at identifying multiple valid QSAR models based on different data-splitting strategies. Finally, a comprehensive virtual screening of a large PFAS dataset was conducted to assess their potency in disrupting thyroid hormone transport. The predictions indicated that more than 7,500 compounds were active with over 100 PFAS potentially causing even greater adverse effects than PFOA. These findings highlight the critical role of integrating New Approach Methodologies (NAM)-based in vitro toxicity testing with multifaceted molecular modeling in assessing the risks associated with PFAS contamination in environmental matrices.

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来源期刊
Journal of Hazardous Materials
Journal of Hazardous Materials 工程技术-工程:环境
CiteScore
25.40
自引率
5.90%
发文量
3059
审稿时长
58 days
期刊介绍: The Journal of Hazardous Materials serves as a global platform for promoting cutting-edge research in the field of Environmental Science and Engineering. Our publication features a wide range of articles, including full-length research papers, review articles, and perspectives, with the aim of enhancing our understanding of the dangers and risks associated with various materials concerning public health and the environment. It is important to note that the term "environmental contaminants" refers specifically to substances that pose hazardous effects through contamination, while excluding those that do not have such impacts on the environment or human health. Moreover, we emphasize the distinction between wastes and hazardous materials in order to provide further clarity on the scope of the journal. We have a keen interest in exploring specific compounds and microbial agents that have adverse effects on the environment.
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