皮肤致敏试验替代方法研究进展

doi:10.3969/j.issn.1001-1803.2019.06.008

摘要/Abstract

摘要：

概述并比较分析了直接肽反应试验（DPRA）、小鼠局部淋巴结试验（LLNA）、KerationSens ^TM、人细胞系激发试验（h-CLAT）和重组人表皮致敏试验等皮肤致敏试验替代方法,并重点介绍了各替代方法的整合研究情况,提出了皮肤致敏试验替代方法的发展前景。

关键词: 皮肤致敏, 替代方法, 进展, 整合

Abstract:

In the present study, skin sensitization alternative methods, such as direct peptide reactivity assay（DPRA）, local lymph node assay（LLNA）, KerationSens ^TM, human cell line activation test（h-CLAT）and reconstructed human epidermis model（RHE model）sensitization test, were summarized, analyzed and compared. The integration of these alternative methods was introduced, and the development prospects of alternative methods for skin sensitization test were prospected.

Key words: skin sensitization, alternative methods, progress, integrated approaches

中图分类号:

R758.2

梅承翰,谭红,杨鸿波,陈蓓蓓,刘师卜,刘婷. 皮肤致敏试验替代方法研究进展[J]. 日用化学工业, 2019, 49(6): 393-397.

MEI Cheng-han,TAN Hong,YANG Hong-bo,CHEN Bei-bei,LIU Shi-bu,LIU Ting. Research progress on alternative methods for skin sensitization tests[J]. China Surfactant Detergent & Cosmetics, 2019, 49(6): 393-397.

图/表 1

表 1

皮肤致敏试验各替代方法比较"

类别	优点	缺点	待测物适用范围	有害结局通路
LLNA	快速、动物使用量少、方法更加完善、灵敏度高、定量检测、便宜	不能很好地区分致敏物和刺激物可导致假阳性^[6]、金属假阴性、放射性核素、环境污染、溶剂对结果影响大、无法区分特定类型的超敏反应^[6]、不能完全避免动物使用	固/液待测物,溶解或不溶待测物	ADME、分子起始事件、应激应答、DC细胞激活、T细胞激活
Keratino- Sens^TM/ LuSens	准确度高、可提供待测物无毒性作用浓度范围	对含酐待测物预测存在问题^[13]、待测物水溶性问题^[26]、代谢能力缺乏^[26]、一些物质可干扰流式分选系统^[26]	可溶或可形成稳定的分散体（如胶体、悬浮液）	分子起始事件、应激应答
h-CLAT/U-SENS	可区分致敏性和刺激性待测物、预测表现好、剂量依赖性	待测物水溶性问题^[26]、代谢能力缺乏^[26]、一些物质可干扰流式分选系统^[26]	可溶或可形成稳定的分散体（如胶体、悬浮液）	分子起始事件、应激应答、DC细胞激活
DPRA	准确度高、操作简单、可批量化检测、重复性好	对待测物溶解性要求高、代谢能力缺乏、不能准确预测组分未知的混合物	单一组分待测物或各组分配比已知的混合物（100 mmol/L）、不可用于金属化合物和含未知成分的混合物	分子起始事件
三维重组人表皮模型	使用方便、来源广、变异性小、具有皮肤类似的代谢能力、简单、快速、便宜、可一次筛选较多物质、实验条件易控制、可取代动物试验	皮肤需现培养,试验安排灵活性较差,气体、喷剂无法检测,无法区别轻微刺激物质,有色物质需调整实验协议	固体、液体、半固体和蜡状物	ADME、分子起始事件、应激应答、DC细胞激活

表 1

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