化学品的潜在系统可用性分类,用于安全评估
René Geci1, Alicia Paini2, Andrew P Worth3
1ESQlabs GmbH, Saterland, Germany; Institute for Systems Medicine with Focus on Organ Interaction, University Hospital RWTH Aachen, Aachen, Germany.
Environment international
|June 28, 2025
概括
本研究引入了一种新方法,使用基于生理学的动力学建模来分类化学物质的潜在系统可用性 (PSA),旨在减少化学安全评估中的动物试验.
科学领域:
- 毒理学 毒理学 毒理学
- 计算化学计算化学
- 药理动力学 药理动力学
背景情况:
- 目前的化学品安全评估面临的局限性是由于越来越多的物质和依赖动物试验.
- 欧洲动物试验替代方法伙伴关系 (EPAA) 提出了一个新的框架,用于系统毒性分类的新方法方法.
- 该框架的一个关键组成部分是按潜在系统可用性 (PSA) 问题对物质进行分类,但缺乏明确的方法.
研究的目的:
- 为潜在系统可用性 (PSA) 问题定义健康保护类.
- 开发和介绍一个定量方法来评估PSA关注.
- 为了解决PSA分类中的概念和实际含糊性.
主要方法:
- 使用高通量生理基动力学 (PBK) 建模.
- 将该方法应用于EPAA NAM设计大赛中的150种化合物.
- 手动注释的化合物用于根据专家判断验证预测的PSA分类.
主要成果:
- 在150种化合物中,成功对139种PSA问题进行了分类.
- 证明了PBK建模的实用性,用于根据毒动因特性的化学物质进行优先或非优先排序.
- 发现大多数化合物需要除单纯的PSA外进行进一步评估,因此需要中等PSA关注分类来进行更广泛的系统毒性评估.
结论:
- 开发的方法为EPAA框架内的PSA关注分类提供了定量方法.
- 毒动力学特性对于优先考虑化学安全评估至关重要.
- 生物活性数据的整合对于该方法和EPAA整体框架的完整评估至关重要.
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