基于in vitro和in silico技术的化学品眼刺激性评价替代方法研究  

Study on the alternative method for assessing eye irritation of chemicals using in vitro and in silico approaches

作　　者：林铌 罗飞亚[1] 曹春然 胡宇驰 Ni Lin;Feiya Luo;Chunran Cao;Yuchi Hu(National Institutes for Food and Drug Control,Beijing 100050,China;State Drug Administration Key Laboratory of Innovative Drug Safety Research and Evaluation,Beijing Institute for Drug Control,Beijing 102206,China;Beijing Key Laboratory of Analysis and Evaluation on Chinese Medicine,Beijing Institute for Drug Control,Beijing 102206,China)

机构地区：[1]中国食品药品检定研究院,北京100050 [2]北京市药品检验研究院,国家药品监督管理局创新药物安全研究与评价重点实验室,北京102206 [3]北京市药品检验研究院,中药成分分析与生物评价北京市重点实验室,北京102206

出　　处：《日用化学工业》2022年第9期1016-1022,共7页China Surfactant Detergent & Cosmetics

摘　　要：建立基于荧光素漏出试验(Fluorescein Leakage test,FL test)和计算机模拟评价(in silico)技术的化学品眼刺激性初步评估和筛选的替代方法,并探讨其替代整体动物眼刺激性试验(Draize test)的可能性。分别采用FL test和Toxtree软件对经济合作与发展组织(the Organization for Economic Co-operation and Development,OECD)推荐的8种实验室能力验证物质的眼刺激性进行检测,并对结果进行分级。同时,分别比较两种方法测定结果的一致性。FL试验在判断受试物是否为严重刺激性/腐蚀性时和在进一步判定物质是否为严重刺激性/腐蚀性、中度刺激性或轻刺激性/无刺激性时,结果均具有较好的一致性(Kappa值为1,P=0.005;Kappa值为0.579,P=0.035)。Toxtree软件预测结果显示其更适合对“轻刺激性/无刺激性”受试物进行初步筛选。FL test是一种有效的眼刺激性评价体外替代方法,具有良好的应用和推广价值,更适用于判定有严重眼刺激性/腐蚀性的化合物,或作为“自上而下”眼刺激性评价分层组合测试策略中首先开展的实验。Toxtree预测结果可作为眼刺激性综合评估的参考数据。The aim of the study was to establish the alternative method for preliminary assessing eye irritation of chemicals using Fluorescein Leakage test(FL test)and Quantitative Structure Activity Relationship(QSAR),to detect and classify the ocular irritation of the recommended substances,and to explore the application value of different alternative methods.Using Toxtree models to predict eye irritation and irritation potency of 8 recommended substances for demonstrating technical proficiency.The test substances were prepared into series of concentrations and exposed with the Madin-Darby canine kidney cell(MDCK)for 1 min to test the percentage of fluorescein leakage(FL/%).The results were categorized according to the classification criteria for assessing eye irritation.Then,the sensitivity,specificity,and accuracy of FL test and Toxtree models were evaluated.Furthermore,the consistency of FL test or Toxtree model was compared with UN-GHS(United Nationas Globally Harmonized System of Classification and Labelling of Chemicals)classification.When FL test is used to distinguish if the test substance belongs to severe irritation/corrosion(GHS Cat.1),the irritation potency of all test substances is concordant with that in GHS classification(Kappa=1,P=0.005).When FL test is used to distinguish if the test substance is severe irritation/corrosion(GHS Cat.1),moderate irritation(GHS Cat.2A)or mild/no irritation(GHS Cat.2B/No Cat.)substances,the irritation potency of all test substances is concordant with GHS classification in the eye irritant potency(Kappa=0.579,P=0.035).The results predicted by Toxtree software demonstrate that it is more suitable to firstly estimate the possible substances with mild/no ocular irritation.The FL test is an effective and valuable alternative method for evaluating eye irritation,and it is more applicable to identify chemicals with severe irritation/corrosion or to be the study firstly carried out using the“Top-Down approach”of the integrated decision-tree testing strategy for eye irritation.Th

关 键 词：眼刺激性 替代方法 体外试验 定量构效关系 荧光素漏出试验 Toxtree软件 

分 类 号：TQ658[化学工程—精细化工]