通过反映生理学年龄算法在生理学基础的毒动力学模型中解释个体间的暴露变异性:用于对di-isobutyl-phthalate的人类风险评估的应用
Seung-Hyun Jeong1, Ji-Hun Jang2, Yong-Bok Lee2
1College of Pharmacy, Sunchon National University, 255 Jungang-ro, Suncheon-si, Jeollanam-do, 57922, Republic of Korea; College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Suncheon-Si 57922, Republic of Korea.
本研究引入了生物年龄算法 (BAA),以改进对危险物质的人类风险评估. 新模型考虑了与年龄相关的毒动力学变异性,提高了准确性,超出了当前一刀切的方法.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 药理动力学 药理动力学
背景情况:
- 目前对环境危害的人类风险评估经常使用一种适合所有人的方法.
- 这些评估经常忽略了与年龄相关的毒性动力学变异性和生理变化.
- 暴露和新陈代谢的个体间差异显著影响健康结果.
研究的目的:
- 通过结合特定年龄的毒性动力学变异性,开发精确的人类风险评估模型.
- 通过考虑生理和代谢波动,超越普遍的风险评估.
- 量化年龄对危险物质毒动学的影响.
主要方法:
- 一项元分析确定了与年龄相关的生理和代谢变化.
- 这些变化被定量建模成生物年龄算法 (BAA).
- 在男性中,BAA与基于生理学的毒动力学 (PBTK) 模型相结合,用于二异布甲酸盐 (DiBP) 和其代谢物单异布甲酸盐 (MiBP).
主要成果:
- 综合BAA-PBTK模型估计了特定年龄的二异布甲酸盐 (DiBP) 外部暴露值.
- 蒙特卡洛模拟显示了个人内部暴露变量的分布.
- 生理因素占了93.41-99.99%的依赖年龄的毒动力学变化,代谢因素贡献了0.01-6.59%.
结论:
- 开发的平台提供了一种逐步的方法来增强毒动力学模型.
- 这种方法解决了解释个体间药理动力学变异性的局限性.
- 它为不同年龄组中各种物质的更合理,更准确的风险评估提供了基础.
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