发展性毒性评估的假设驱动方法:使用机械信息来告知测试
George Daston1, Matthew Burbank2, Florian Gautier2
1Global Product Stewardship - Human Safety, The Procter & Gamble Co., Mason, OH 45040, USA.
Reproductive toxicology (Elmsford, N.Y.)
|December 1, 2025
概括
了解作用模式 (MoA) 增强了发育毒性测试. 这种方法使用机械数据来进行更灵活,更有效的化学安全评估.
科学领域:
- 毒理学 毒理学 毒理学
- 药理学 药理学是指药理学的学科.
- 计算化学计算化学
背景情况:
- 传统的发育性毒性测试使用动物模型和标准化协议.
- 新兴的机械学数据允许改进模型选择和预测结果.
- 使用化学信息学和生物相似性进行交叉阅读的方法是化学评估的关键.
研究的目的:
- 探索如何理解作用模式 (MoA) 可以完善发育性毒性评估.
- 证明向更灵活,以假设为导向,资源高效的测试策略的转变.
- 要突出体内,体外和计算方法的整合.
主要方法:
- 调查试剂的作用方式 (MOA).
- 利用与化学信息学的交叉读取原则进行模拟选择.
- 使用高通量选 (例如,ToxCast) 和转录组学.
- 为人类相关的生物模型利用诱导的多能干细胞.
主要成果:
- 了解作用模式可以在化学序列中识别活动悬崖.
- 代谢数据可以减少对所有类似化学类型的测试的需要.
- 基因表达分析揭示了类似化合物之间的药理学差异.
- 机械洞察力使得以假设为导向的测试设计成为可能.
结论:
- 一种机理主义的,以假设为导向的方法为传统的发育毒性测试提供了更灵活和更有效的替代方案.
- 多种数据 (in silico,in vitro,omics) 的整合可以提高预测准确度.
- 这种范式转变支持更有针对性和资源意识的化学安全评估.
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