应用小鼠局部淋巴结试验(LLNA:DA)对13种化学物刺激性和致敏性的评价  

Study to evaluate chemical stimulation and sensitization using the local lymph node test in mice(LLNA:DA)

作　　者：陈宁 黄泽愉 孙晓 谢天柱 陈润桦 李俊鹏 冼静雯 吴熙 刘逸茗 秦美蓉 王平 王晓炜 鲁艺 CHEN Ning;HUANG Ze-yu;SUN Xiao;XIE Tian-zhu;CHEN Run-hua;LI Jun-peng;XIAN Jing-wen;WU Xi;LIU Yi-ming;QIN Mei-rong;WANG Ping;WANG Xiao-wei;LU Yi(Shenzhen Institute for Drug Control,NMPA Key Laboratory for Monitoring and Evaluation of Cosmetics,GDMPA Key Laboratory of Animal Alternative Testing Technology on Cosmetics,Shenzhen Guangdong 518057,China)

机构地区：[1]深圳市药品检验研究院国家药品监督管理局化妆品监测评价重点实验室广东省药品监督管理局化妆品动物替代试验技术重点实验室,广东深圳518057

出　　处：《毒理学杂志》2022年第3期249-253,257,共6页Journal of Toxicology

基　　金：深圳市科技创新委科技计划项目-基础研究(JCYJ20180302150138733);广东省药品监督管理局科技引导扶持项目(2018YDB32);广东省药品监督管理局重点实验室(2018ZDB13);深圳市药品检验研究院重点学科团队建设项目。

摘　　要：目的利用BALB/c小鼠对13种不同浓度化学物进行局部淋巴结试验(LLNA:DA)检测,评价受试物皮肤刺激性和致敏性,为LLNA:DA法应用于致敏性检测提供数据支持。方法采用BALB/c小鼠LLNA:DA法,对13种化学物进行评价,并将结果与国际权威机构ICCVAM结果对照分析。结果2,4-二硝基氯苯、丁子香酚、3-氨基苯酚、异丁香酚、反式肉桂醛、甲醛、戊二醛、二氯化钴、六水硫酸镍和重铬酸钾等10种化学物部分浓度组或全部浓度组的刺激指数SI值>1.8,致敏阳性;异丙醇、间苯二甲酸二甲酯和水杨酸甲酯的刺激指数SI<1.8,致敏阴性。根据SI指数计算EC1.8(%),进一步进行致敏分级,致敏性预测准确率为100%(13/13),阳性致敏物预测率为100%(10/10),阴性致敏物预测率为100%(3/3),致敏分级准确率为85%(11/13)。结论在本试验条件下,BALB/c小鼠LLNA:DA法可较好地评估化学物的致敏性,适用于未来化学物致敏性检测。Objective To evaluate the sensitization of 13 samples with murine local lymph node assay(LLNA:DA)test method and to verify whether the BALB/c mice could be used in LLNA:DA test.Methods The BALB/c mouse LLNA:DA method was used to evaluate 13 chemicals,and the result were compared with the result of the international authoritative organization ICCVAM.Results The stimulation index SI value of 2,4-dinitrochlorobenzene,eugenol,3-aminophenol,isoeugenol,trans-cinnamaldehyde,formaldehyde,glutaraldehyde,cobalt dichloride,nickel sulfate,potassium dichromate in partial or all concentration groups of the 10 chemicals is>1.8,indicating positive sensitization;The stimulation index SI of isopropyl alcohol,dimethyl m-phthalate and methyl salicylate was<1.8,indicating negative sensitization.According to SI index,EC1.8(%)was calculated and further sensitization classification was carried out.The accuracy of sensitization prediction was 100%(13/13),positive sensitizer prediction rate was 100%(10/10),negative sensitizer prediction rate was 100%(3/3),and the accuracy of sensitization classification was 85%(11/13).Conclusion The BALB/c mouse LLNA:DA method can be used to evaluate the sensitization of chemicals in the future.

关 键 词：局部淋巴结试验 皮肤致敏性 LLNA-DA 

分 类 号：R114[医药卫生—卫生毒理学] R758[医药卫生—公共卫生与预防医学] R99