在老鼠中,摩尔福林的毒动力学和质量平衡
Aleksandra Piotrowski1, Saïd Kinani2, Fabrice Nesslany3
1EDF - Industrial Toxicology Division at EDF, General Direction of Safety and Health, Paris, France.
吗啡 (MOR) 暴露带来风险,因为它可以在体内形成致癌物N-尼特罗斯 (NMOR). 这项研究跟踪了MOR.
科学领域:
- 毒理学 毒理学 毒理学
- 药理动力学 药理动力学
- 致癌的发生是致癌的产生.
背景情况:
- 吗波林 (MOR) 被广泛使用,导致人类显著的暴露风险.
- 摄入的MOR可以通过内源性化形成N-nitrosomorpholine (NMOR),这是一种潜在的人类致癌物.
- 了解MOR毒动力学对于评估NMOR相关的健康风险至关重要.
研究的目的:
- 在大鼠口服后,研究吗啡 (MOR) 的毒动力学.
- 通过测量其代谢物N-nitrosohydroxyethylglycine (NHEG) 来评估MOR内源性N-化程度.
- 为了确定放射性标记的MOR的质量平衡和分泌概况.
主要方法:
- 口服14C放射标记的MOR和化 (NaNO2) 给斯普拉格-道利大鼠.
- 量化血液,血,尿液和便中的放射性物质,以确定质量平衡和毒动力学概况.
- 使用高性能液体染色学 (HPLC) 作为内源性化生物标志物,测量尿液中的N-化乙基 (NHEG).
主要成果:
- MOR在30分钟内迅速达到血中度的峰值,并且很快被清除 (70%在8小时内).
- 大多数放射性物质通过尿液 (80.9%) 排泄,主要是作为不变的MOR (84%的回收剂量).
- 通过NHEG检测证实了MOR的内源性化,最大转化率为13.3%,受MOR/NaNO2比率的影响.
结论:
- 在老鼠中,MOR呈现出快速的吸收和排泄,不变的MOR在尿液中的分泌是主要的途径.
- 该研究证实了MOR的内源性化,证明了NHEG的形成,并表明转化率取决于反应剂度.
- 这些发现有助于更好地了解内源性N-nitrosomorpholine生产,这与人类致癌物质风险评估有关.
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