以NAM为基础对发育神经毒性影响进行风险评估,用pyrifosos说明
Anne Zwartsen1, Joost Westerhout1, Shensheng Zhao1
1Centre for Prevention, Lifestyle and Health, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
ALTEX
|October 23, 2025
概括
新方法方法 (NAMs) 可以改善化学风险评估,但数据推断中的不确定性需要量化. 这项研究强调了使用NAM用于发育性神经毒性 (DNT) 风险评估的挑战.
科学领域:
- 毒理学和风险评估
- 在 Vitro 和 In Silico 方法中.
- 发育神经毒性 发育神经毒性
背景情况:
- 新方法方法 (NAM) 为化学风险评估提供了动物试验的替代方案,旨在缩短交付时间并提高人类健康的预测能力.
- 在监管风险评估中实施NAM需要解决和量化固有的不确定性,特别是在推断数据时.
- 发育神经毒性 (DNT) 是一个关键的终点,NAM显示有前途,但面临额外推断的挑战.
研究的目的:
- 通过使用NAM,对pyrifos DNT进行理论风险评估,识别和量化数据推断中的不确定性.
- 评估用于估计人类健康风险的体外数据和生理基动力学 (PBK) 模型的应用.
- 为了获得DNT的体外健康值,并将其与流行病学数据进行比较.
主要方法:
- 利用细胞活力的分化人类神经元前代细胞作为DNT的代理.
- 开发了早期怀孕的生理基动力学 (PBK) 模型,以实现定量化体外到体外抽取 (qIVIVE).
- 在pyrifos暴露后获得了DNT发病的体外基于健康的值.
主要成果:
- 在DNT的体外基于健康的值得出.
- 这一推导值超过了从流行病学数据中得出的与DNT发病相关的孕产妇暴露水平.
- 该研究确定了在基于NAM的DNT风险评估中需要改进的关键领域.
结论:
- 目前基于NAM的DNT风险评估需要改进,特别是体外终点选择和分析开发.
- 量化关键事件和不良结果之间的关系对于NAM的监管实施至关重要.
- 需要进一步的研究来提高化学风险评估NAM的可靠性和监管接受度.
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