使用不良结果途径进行体外数据的定量建模,用于对人类肺功能下降的风险评估
Alain Sewer1, Marja Talikka1, Florian Calvino-Martin1
1PMI R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
Toxicology letters
|February 13, 2024
概括
计算模型预测,与可燃香烟相比,加热烟草制品 (THS) 的肺功能风险降低. 这种方法使用体外数据和不良结果途径 (AOP) 来评估烟草产品的安全性.
科学领域:
- 毒理学 毒理学 毒理学
- 计算生物学 计算生物学
- 呼吸系统医学 呼吸系统医学
背景情况:
- 对新型烟草产品缺乏流行病学数据.
- 不良结果途径 (AOPs) 将分子事件与不良健康结果联系起来.
- 试验室模型对于预测暴露在有毒物质中的人类健康风险至关重要.
研究的目的:
- 从体外有毒物质暴露数据开发计算模型来预测人类疾病风险.
- 评估与可燃香烟 (CC) 烟雾相关的肺功能下降风险与烟草加热系统 (THS) 气溶相比.
- 为烟草制品的综合测试和评估建立一个框架.
主要方法:
- 利用先进的体外器官类型的气道模型暴露在CC烟雾和THS气溶中.
- 应用了AOP框架,将氧化应激与肺功能下降联系起来.
- 综合体内数据与人体数据的粘膜干净度 (MCC) 和肺功能.
主要成果:
- 数学建模预测,与CC暴露的培养相比,THS暴露的培养中有较低的纤维细胞跳动频率 (CBF) 和MCC的风险.
- 预测扩展到肺功能下降,表明THS使用与持续吸烟相比风险降低.
- 该方法证明了AOP和风险评估综合建模的实用性.
结论:
- 使用AOPs的计算建模表明,与CC烟相比,THS气溶对肺功能下降的风险较低.
- 开发的方法为对烟草产品的监管评估提供了基础.
- 在体外到体外抽取是评估新兴烟草产品的可行策略.
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