在发育和成人神经毒性测试新方法的最新进展和当前挑战
Melania Maria Serafini1, Sara Sepehri2, Miriam Midali3
1Department of Pharmacological and Biomolecular Sciences, "Rodolfo Paoletti", Università degli Studi di Milano, Milan, Italy. melania.serafini@unimi.it.
Archives of toxicology
|March 14, 2024
概括
新方法方法 (NAMs) 为评估成人和发育神经毒性提供了动物试验的替代方案. 虽然有希望,但测试电池集成和验证等挑战阻碍了它们的全面监管实施.
科学领域:
- 毒理学 毒理学 毒理学
- 神经科学是一个神经科学.
- 监管科学 监管科学
背景情况:
- 成人神经毒性 (ANT) 和发育神经毒性 (DNT) 的评估传统上依赖于动物试验,以了解对神经系统的毒性影响.
- 新方法方法 (NAMs) 正在作为替代的非动物测试策略获得引.
- 像经合组织这样的监管机构促进了验证的替代系统,但目前的ANTT和DNT指南仍然主要依赖于动物研究.
研究的目的:
- 审查最近在ANT和DNT评估的NAM中取得的进展.
- 突出这些替代方法的监管实施的潜在和当前挑战.
- 评估体外电池的发育神经毒性 (DNT IVB) 状态作为最初的NAM步骤.
主要方法:
- 关于神经毒性NAM最近进展的文献综述.
- 对当前监管环境的分析以及ANT和DNT的指导方针.
- 讨论关键问题,包括测试电池集成,实验室间可转移性和方法验证.
主要成果:
- 包括体外和体内非哺乳动物模型 (例如斑马鱼,C. elegans) 在内的NAM显示出神经毒性评估的前景.
- 该DNT IVB被介绍为NAM实施的基本步骤.
- 仍然存在重大挑战,包括需要集成测试电池和强大的验证.
结论:
- 在神经毒性评估中,NAM为减少和取代动物试验提供了一条可行的途径.
- 解决跨学科性,可转移性和验证性的问题对于NAMs的完全监管接受至关重要.
- 为了在ANT和DNT评估中广泛采用NAM,进一步开发和验证至关重要.
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