基于AOP原理的皮肤致敏测试替代方法进展
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摘要
皮肤局部接触某些化学品可引起免疫性皮肤反应,传统的皮肤致敏试验采用豚鼠进行,在3R原则和现代科技发展的推动下,多项动物试验的优化方法和替代方法被开发并通过验证认可,如LLNA、DPRA、KeratinoSens~(TM)和CLAT等。替代方法的开发适应了日益增加的化学品和化妆品的致敏筛查需求。目前,基于有害结局通路概念开发更符合皮肤生物学机制的替代方法,应用整合测试策略在考虑证据权重和兼顾成本效益的前提下,将适用范围不同的体外方法方法进行组合,是现阶段皮肤致敏替代方法研发的重要方向。
Allergic contact dermatitis,or skin sensitization,is an inflammatory reaction controlled by the immune response induced by foreign substances.Animal models such as the guinea pig maximization test were traditionally used to estimate whether a chemical has the potential to induce skin sensitization in humans.Under the promote if 3Rs principle and modernization technologies,several refined animal testing and in vitro screening methods have been developed for identifying potential contact allergens,such as the murine local lymph node assay(LLNA),DPRA,KeratinoSens? and h-CLAT.The development of in vitro methods is suitable to predict sensitization hazard from chemicals and cosmetics.More recently,the theory underlying this approach has been formalized in the "adverse outcome pathway"(AOP)paradigm,a concept that links the individual events starting from the molecular initiating event(MIE) to the result at the level of the whole organism,integrated test strategy that take "weight of evidence" and "cost-effectiveness" into consideration for the AOP-based skin sensitization is the important goal for future.
引文
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