尼托胺的可接受摄入量应考虑分子重量的变化:史泰基度DNA损伤的含义
Jonathan Fine1, Leonardo Allain1, Joerg Schlingemann2
1Merck & Co., Inc., Rahway, NJ, USA.
Regulatory toxicology and pharmacology : RTP
|October 7, 2023
概括
药品中N-亚胺 (NA) 的可接受摄入限值应该是以毛囊为基础的,而不是以质量为基础的. 通过考虑分子重量和变异原体潜力,修订摩尔尺度的极限可以确保准确的健康保护.
科学领域:
- 制药化学 制药化学 制药化学
- 毒理学 毒理学 毒理学
- 药用化学 医学化学
背景情况:
- N-胺胺 (NA) 是药品中发现的致变性化合物.
- 对于NA的当前可接受摄入量 (AI) 极限通常是基于质量的.
- 这种基于质量的方法可能不会准确地反映毒理风险.
研究的目的:
- 为了证明在摩尔尺度上表达制药NAsAI的必要性.
- 建议对未知的尼托胺提议一个修订后的默认AI.
- 提供与分子重量 (MW) 纠正的AI,用于氨酸药物物质相关杂质 (NDSRI).
主要方法:
- 重新计算欧洲药物管理局 (EMA) 默认的AI,以摩尔为基础的未知尼托胺.
- 对于NDSRI预先分配的AI应用MW校正.
- 分析尼特罗斯基,DNA突变和分子量之间的机制关系.
主要成果:
- 对于未知的尼托胺,建议修订了163 pmol/day的默认AI.
- 针对特定的NDSRI提供了MW校正的AI值.
- 该研究强调了基于的AI对于准确的风险评估的重要性.
结论:
- 在摩尔尺度上表达AI或对MW进行校正对于NAs至关重要.
- 这种方法与对NA突变性有机学的理解相一致.
- 在监管层面接受以为基础的极限值将提高NDSRI的健康保护和可行性.
关键词:
18 ng人工智能默认使用可以接受的摄入量致癌性 致癌性 致癌性关注的ICH M7队列N-尼胺氨基化合物 的含量这是NDSRI的NDSRI.亚胺酸氨酸的含量百分位数是一个百分位数.阅读横向的阅读.风险评估 风险评估 风险评估TD ((50) 的意思.毒理学 毒理学 毒理学更多相关视频
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