在剂量反应评估中纳入新方法 (NAM) 数据:未来是现在!
En-Hsuan Lu1, Ivan Rusyn1, Weihsueh A Chiu1
1Interdisciplinary Faculty of Toxicology and Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.
概括
新方法方法 (NAMs) 可以通过整合所有关键剂量反应模块 (KDMs) 来增强监管毒性评估. 该框架揭示了NAM超越POD确定和毒动力学的机会,改善人类健康保护.
科学领域:
- 毒理学和化学风险评估
- 计算毒理学和体外检测方法
- 监管科学 监管科学
背景情况:
- 传统的剂量反应评估依赖于体内数据和默认假设.
- 新方法方法 (NAMs) 提供了改进化学评估的机会.
- 需要一个统一的框架来将NAM整合到剂量反应评估中.
研究的目的:
- 评估NAM在剂量反应评估的概念框架中的潜在利用.
- 确定将NAM集成到关键剂量响应模块 (KDM) 的机会.
- 打破传统方法和NAM之间的二分法.
主要方法:
- 开发了剂量反应评估的五个模块框架 (KDM):POD确定,物种间毒动力学/毒动力学,物种内部毒动力学和毒动力学.
- 审查了现有的NAM (in silico,in vitro,in vivo) 以在KDM中适用.
- 组织剂量反应评估为KDM和Tier (0-3) 的矩阵,基于精度和可靠性.
主要成果:
- 目前,NAM被推广用于POD确定 (KDM1) 和毒动力学 (KDM5).
- KDM-Tier矩阵揭示了在所有KDM中整合NAM的更广泛的直接机会.
- 在体外剂量测量和量化毒力学方面存在NAM的关键需求.
结论:
- 将NAM集成到所有KDM中,可以实现更高的吞吐量,减少动物使用,以及更多基于科学的毒性值.
- NAM可以显著提高监管剂量反应评估,以改善人类健康保护.
- 进一步开发用于剂量测量和毒性动力学的NAM至关重要.
相关概念视频
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00:59Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis
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