基于对药物的经验性暴露,开发化学品的毒理学关注的内部值 (iTTC)
Toshihide Takeshita1, Yuuko Nukada2, Shota Nakagawa2
1R&D, Safety Science Research, Kao Corporation, Kanagawa, 210-0821, Japan.
Regulatory toxicology and pharmacology : RTP
|April 17, 2025
概括
风险评估的毒理关注门 (TTC) 方法现在包括内部TTC (iTTC),标准化化学物质暴露. 提出了0.6nM的全身毒性新型iTTC,使得无动物风险评估.
科学领域:
- 毒理学 毒理学 毒理学
- 风险评估 风险评估
- 药理动力学 药理动力学
背景情况:
- 毒理学关注的门 (TTC) 是一种风险评估方法,使用具有有限毒理学数据的化学品的低水平暴露值.
- 传统的TTC对全身毒性依赖于来自动物研究的外部剂量,通过各种管理途径.
- 跨路线的暴露标准化对于更广泛的TTC应用至关重要.
研究的目的:
- 将TTC概念从外部扩展到内部 (血液) 剂量,引入内部TTC (iTTC).
- 提出基于人类治疗药物度的全身毒性新 iTTC 值.
- 为了使化学物质暴露的风险评估更加标准化,并可能不涉及动物.
主要方法:
- 作为毒理学起点,利用了来自人用药物的耐受性血/血清药物度.
- 为无效度推导出0.6nM的新 iTTC 值.
- 使用正常分布的第五百分位数和不确定性系数来确定iTTC.
主要成果:
- 针对系统性毒性,提出了0.6nM的新型内部TTC (iTTC).
- 这个iTTC通过关注内部 (血液) 度来规范暴露.
- 该方法允许在没有直接动物试验的情况下进行风险评估.
结论:
- 拟议的iTTC方法通过标准化内部曝光来增强TTC框架.
- 预测血液中的化学物质度并将其与iTTC进行比较,为系统性毒性风险评估提供了一条可行的途径.
- 这种方法有可能减少对动物性毒性测试的依赖.
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