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评估一个非动物工具箱,通过人类吸入安全的不良结果途径来评估非动物工具箱

Renato Ivan de Ávila¹, Iris Müller¹, Hugh Barlow¹

¹Safety, Environmental and Regulatory Science (SERS), Unilever, Colworth Science Park, Sharnbrook, Bedfordshire, United Kingdom.

Frontiers in toxicology

|March 10, 2025

概括

这项研究使用人类细胞模型和计算工具开发了一种非动物测试方法,用于化学肺部安全. 新方法准确预测了各种化学品的肺部风险,支持更安全的化学品评估.

科学领域:

毒理学毒理学毒理学
在体外毒理学.
计算毒理学计算毒理学

背景情况:

下一代风险评估 (NGRA) 需要强大的非动物方法.
评估化学诱导的肺毒性对人类健康至关重要.
现有的方法往往依赖于动物试验,需要采用替代方法.

研究的目的:

评估一种非动物试验策略,以评估化学物质诱导的肺部影响.
将人体体体外呼吸道模型与风险评估的计算工具相结合.
在NGRA背景下建立化学肺安全评估的框架.

主要方法:

使用MucilAirTM-HF和EpiAlveolarTM人类呼吸道模型进行12天的重复物质暴露.
分析了组织完整性,细胞因子/化学因子分泌和生物活性读数的转录组学.
使用体外起点 (PoD) 和人类暴露估计 (肺部沉积或Cmax) 计算的生物活性暴露比率 (BER).

主要成果:

在14种暴露场景中,非动物方法成功评估了11种基准化学品.
在大多数低风险情景中,PoDs超过了人类暴露水平.
在高风险场景中观察到PoDs和暴露指标之间的重叠,表明潜在的危险.

结论:

结合计算和体外新方法方法 (NAMs),为化学肺安全提供了相关的生物覆盖.
不良结局途径 (AOP) 对于为肺毒性评估提供信息是有价值的.
这种非动物方法支持NGRA的化学肺安全.

关键词:

生物活性的暴露比率.吸入风险评估吸入风险评估模拟肺部暴露的模型.肺部毒性肺部毒性肺部毒性新方法方法论新方法方法论非动物试验的测试.起点的起点是出发点.

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