体外暴露评估提高双酚A替代品的危害等级

IF 4.1 3区医学 Q2 CHEMISTRY, MEDICINAL

Chemical Research in Toxicology Pub Date : 2026-10-19 Epub Date: 2026-09-30 DOI:10.1021/acs.chemrestox.6c00300

Luise Henneberger, Sophia Bardehly, Arina Kremser, Vanessa Srebny, Beate I. Escher

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引用次数: 0

摘要

体外毒性数据可用于有问题的塑料化学品双酚A（BPA）及其替代化学品的比较危害评估。危害评估完全基于双酚a替代品的名义效应浓度，但由于其物理化学性质和稳定性的多样性，这可能导致不准确的危害排名。在本研究中，测定了双酚a及其24种替代品的化学稳定性和自由溶解浓度（Cfree）。发现BPA和22种替代品在生物测定培养基中稳定达48小时。BPA的二缩水甘油醚（BADGE）在培养基中完全降解。对于BPPH，观察到损失高达37%。利用物质平衡模型推导出生物测定培养基中稳定化学物质的Cfree。为了模型验证，生物测定培养基中的Cfree，以及与蛋白质和膜脂的结合，测量了BPA和15种替代品。实验确定的Cfree与模型预测的一致程度在10倍之内。在两个代表性终点（雌激素受体α的激活和线粒体膜电位的抑制）上，根据名义（REPnom）和自由溶解效应浓度（REPfree）计算BPA替代品与BPA的相对效价（repps）。对于亲水性和中度疏水性的双酚a替代品，REPnom和REPfree符合得很好。对于疏水和高蛋白结合的替代品，如TCBPA或BPAF， REPfree比REPnom高147倍。bp - mibk具有最高的基于REPnom的雌激素潜力，但高蛋白结合的BPAF被鉴定为最有效的基于REPnom。TCBPA的雌激素潜能低于基于REPnom的BPA(0.11)，但基于REPfree的BPA（12.8）比BPA更强。本研究的结果强调需要对不同的体外暴露条件进行校正，以实现准确的危害排序。

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In Vitro Exposure Assessment Improves Hazard Ranking of Bisphenol A Alternatives

In vitro toxicity data can be used for comparative hazard assessment of the problematic plastic chemical bisphenol A (BPA) and its replacement chemicals. Hazard assessment is exclusively based on nominal effect concentrations of the BPA alternatives, but due to their diversity of physicochemical properties and stability, this may lead to inaccurate hazard ranking. In the present study, chemical stability as well as freely dissolved concentrations (C_free) were determined for BPA and 24 of its alternatives. BPA and 22 alternatives were found to be stable in bioassay medium for up to 48 h. The diglycidyl ether of BPA (BADGE) was completely degraded in medium. For BPPH, a loss of up to 37% was observed. A mass balance model was used to derive C_free of the stable chemicals in the bioassay medium. For model validation, C_free in bioassay medium, as well as binding to proteins and membrane lipids, was measured for BPA and 15 of the alternatives. Experimentally determined C_free agreed with model predictions within a factor of 10. Relative effect potencies (REPs) of the BPA alternatives compared to BPA were calculated based on nominal (REP_nom) and freely dissolved effect concentrations (REP_free) for two representative end points (activation of estrogen receptor α and inhibition of mitochondrial membrane potential). For hydrophilic and moderately hydrophobic BPA alternatives, REP_nom and REP_free agreed well. REP_free was up to 147× higher compared to REP_nom for hydrophobic and highly protein-bound alternatives like TCBPA or BPAF. BP-MIBK had the highest estrogenic potential based on REP_nom, but the highly protein-bound BPAF was identified as most potent based on REP_free. TCBPA has a lower estrogenic potential than BPA based on REP_nom (0.11), but based on REP_free (12.8), it is more potent than BPA. The results of the present study highlight the need to correct for different in vitro exposure conditions to allow accurate hazard ranking.

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来源期刊

Chemical Research in Toxicology 医学-毒理学

CiteScore

7.90

自引率

7.30%

发文量

215

审稿时长

3.5 months

期刊介绍： Chemical Research in Toxicology publishes Articles, Rapid Reports, Chemical Profiles, Reviews, Perspectives, Letters to the Editor, and ToxWatch on a wide range of topics in Toxicology that inform a chemical and molecular understanding and capacity to predict biological outcomes on the basis of structures and processes. The overarching goal of activities reported in the Journal are to provide knowledge and innovative approaches needed to promote intelligent solutions for human safety and ecosystem preservation. The journal emphasizes insight concerning mechanisms of toxicity over phenomenological observations. It upholds rigorous chemical, physical and mathematical standards for characterization and application of modern techniques.