基于替代毒理学的有机氟化物全身暴露毒性和局部刺激性研究  

Study on Systemic Exposure Toxicity and Local Irritation of Organic Fluorides Based on Alternative Toxicology

作　　者：万旺军 姚佳妮 邓同乐[2] 陈有为 何坚刚 王琛 WAN Wangjun;YAO Jiani;DENG Tongle;CHEN Youwei;HE Jiangang;WANG Chen(Technology Centre of Hangzhou Customs District P.R.China,Hangzhou 311208,China;China Jiliang University,Hangzhou 310018,China;Technology Centre of Ningbo Customs District P.R.China,Ningbo 315000,China)

机构地区：[1]杭州海关技术中心,浙江杭州311208 [2]中国计量大学,浙江杭州310018 [3]宁波海关技术中心,浙江宁波315000

出　　处：《生物化工》2025年第1期47-52,共6页Biological Chemical Engineering

基　　金：浙江省重大社会公益科技计划项目(2024C03258)。

摘　　要：目的:基于3Rs原则,评价不同有机氟化物全身暴露和局部刺激毒性的替代试验和在体动物试验方法。方法:采用MCF-7乳腺癌细胞株毒性试验替代毒理学评价中的小鼠灌胃染毒试验,以及用人成纤维细胞毒性试验替代家兔眼和皮肤刺激试验,比较不同受试物的全身暴露毒性和局部刺激性强弱。结果:在乳腺癌细胞株染毒试验中,2,4-二氟硝基苯毒性大于邻氟硝基苯;人成纤维细胞染毒试验中,对氟苯腈的刺激性大于3,5-二氟氯苯。替代试验结果与经口小鼠急性毒性、家兔眼和皮肤刺激试验结果一致。结论:体外替代毒理学试验结果与动物验证数据与可查氟化物的毒性/刺激性趋势一致,表明该替代试验对氟化物的全身暴露毒性/局部刺激性具有良好的预测性。Objective:To evaluate alternative tests and in vivo animal test methods for systemic exposure and local irritation toxicity of different organic fluorides based on the 3Rs principle.Methods:The toxicity test of MCF-7 breast cancer cell line is used instead of the toxicity test of mice in toxicology evaluation,and the toxicity test of human fibroblast cells is used instead of rabbit eye and skin irritation test,and the systemic exposure toxicity and local irritation of different test subjects are compared.Results:In the breast cancer cell line infection test,the toxicity of 2,4-difluoronitrobenzene is greater than that of o-fluoronitrobenzene.In the human fibroblast poisoning test,the irritation of 4-fluorobenzonitrile is greater than that of 3,5-difluorochlorobenzene.The results of the surrogate test are consistent with the results of acute toxicity in oral mice,rabbit eye and skin irritation.Conclusion:The results of in vitro alternative toxicology test and animal validation data are consistent with the toxicity/irritation trend of fluoride,indicating that the substitution test has a good predictive effect on systemic exposure toxicity/local irritation of fluoride.

关 键 词：有机氟化物 全身毒性 局部刺激性 替代毒理学 

分 类 号：X171[环境科学与工程—环境科学]