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使用NAMs对重复剂量毒性进行化学品分类的框架
J E Doe1, P Botham2, D Holland3
1School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
Archives of toxicology
|May 24, 2025
概括
一个新的分类系统使用非动物方法对化学毒性进行分类,评估生物活性和生物可用性. 这一框架有助于将化学品分为低,中或高关注级别,以确保更安全的使用.
科学领域:
- 毒理学和化学安全
- 在和体外毒理学中.
- 监管科学 监管科学
背景情况:
- 美国环保局的"NAM Designathon 2023"旨在开发一种使用非动物方法的化学品分类系统.
- 现有的系统往往依赖于动物试验,需要替代方法来评估人类的毒性.
- 整合多个证据线的分层方法对于稳健的化学安全评估至关重要.
研究的目的:
- 开发和展示基于新方法方法 (NAMs) 的人类系统性毒性分类系统,重点关注重复剂量毒性.
- 根据生物活性和生物可用性,将化学品分为三个关注级别:低,中,高.
- 将 in silico 预测,体外生物可用性和生理基动力学 (PBK) 建模以及体外生物活性测试整合到一个连贯的框架中.
主要方法:
- 使用in silico (Q) SAR模型预测毒性终点和识别潜在危险.
- 采用了三种毒动力学 (TK) 模型来模拟14天的血Cmax以评估生物可用性.
- 使用基于强度 (AC50值) 和ToxCast.的体外检测结果严重性的矩阵对生物活性进行分类.
主要成果:
- 成功地应用了开发的框架,将12种化学品分为三个关注级别 (低,中,高).
- 证明了使用将生物活性和生物可用性纳入化学分类的矩阵方法的可行性.
- 这些结果符合EPAA设计马拉松的目标,即建立基于NAMs的毒性分类系统.
结论:
- 拟议的基于NAMs的分类系统有效地将化学品分类为不同级别的人类系统毒性关注.
- 关于测试范围,框架分类定义以及整合到分层评估策略中,需要进一步细化.
- 该研究强调了NAMs在支持监管决策和减少对动物试验的依赖方面的潜力.
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