在风险评估中使用动力学衍生最大剂量水平的新方法方法 - - 一个用阿菲多皮洛的案例研究
Anne E Loccisano1, Elaine Freeman2, Adriana Doi3
1Exponent Inc, Alexandria, VA, 22314, USA.
Regulatory toxicology and pharmacology : RTP
|June 5, 2023
概括
这项研究引入了一种使用动力学衍生最大剂量 (KMD) 的新方法,以评估诸如阿菲多皮洛 (afidopyropen) 等杀虫剂对人类健康的慢性饮食风险. 这种方法减少了动物试验,同时可靠地确定了健康保护水平.
科学领域:
- 环境毒理学环境毒理学
- 风险评估方法 风险评估方法
- 杀虫剂安全评价 杀虫剂安全评价
背景情况:
- 传统的慢性饮食人类健康风险评估 (HHRA) 基于广泛的毒理学数据.
- 当前的HHRA实践往往优先考虑危害特征,而不是暴露信息.
- 现有的方法可能会产生比定义健康保护终点所需的更多数据.
研究的目的:
- 介绍一篇关于使用基于风险21的方法治疗慢性饮食HHRA的阿菲多皮洛 (AF) 的案例研究.
- 展示一种新方法方法 (NAM) 使用动力学衍生最大剂量 (KMD) 来确定健康保护起点 (PoD).
- 为了展示NAM如何减少HHRA的动物试验要求.
主要方法:
- 应用基于风险的21框架用于案例研究分析.
- 通过代谢途径和来确定动力学衍生最大剂量 (KMD).
- 在HHRA中使用KMD作为替代PoD.
主要成果:
- 通过KMD,NAM有效地确定了afidopyropen的健康保护性PoD.
- 这种方法大大减少了对广泛毒理学测试的需求.
- 在90天的老鼠和发育研究中证明非基因毒性和KMD保护足以替代PoD使用.
结论:
- 动力学衍生最大剂量 (KMD) 为慢性饮食HHRA提供了可行的替代PoD.
- 新方法方法 (NAM) 可以简化风险评估过程,尽量减少动物使用.
- 通过使用NAM,可以描述阿菲多皮洛的慢性饮食风险,从而支持监管效率.
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