栀子苷的危害评估和健康指导值推导  

Hazard assessment and derivation of health-based guidance value for geniposide

作　　者：邱雪娇 李强 张磊[1] 李琦 黄雅琳 覃思[2] 包汇慧 QIU Xue-jiao;LI Qiang;ZHANG Lei;LI Qi;HUANG Ya-lin;QIN Si;BAO Hui-hui(Chinese Academy of Medical Science Research Unit(No.2019RU013),NHC Key Laboratory of Food Safety Risk Assessment,China National Center for Food Safety Risk Assessment,Beijing 100022,China;Hunan Agricultural University,Hunan 410125,China;Dandong Zhen'an District Center for Disease Control and Prevention,Liaoning 118003,China)

机构地区：[1]中国医学科学院食品安全创新单元(2019RU013),国家卫生健康委员会食品安全风险评估重点实验室,国家食品安全风险评估中心,北京100022 [2]湖南农业大学,湖南长沙410125 [3]丹东市振安区疾病预防控制中心,辽宁丹东118003

出　　处：《毒理学杂志》2024年第3期199-206,共8页Journal of Toxicology

基　　金：国家重点研发计划资助(2023YFF1103804);国家食品安全风险评估中心高层次人才队伍建设项目。

摘　　要：目的根据现有毒理学资料,在系统文献检索的基础上开展栀子苷对健康影响的危害评估,并基于基准剂量(benchmark dose,BMD)法推导栀子苷的健康指导值(health-based guidance value,HBGV)。方法采用系统文献检索方法(systematic literature search,SLS)收集栀子苷毒理学资料,利用ToxRTool工具对纳入的文献进行质量评价,选取毒理学数据评级最高的文献应用基准剂量法测算关键效应和剂量,结合不确定系数推导栀子苷的健康指导值。结果共纳入10篇栀子苷毒性文献,毒性研究集中在肝、肾毒性,经毒理学可靠性评价最终选取1篇26周大鼠经口毒性试验文献,得出栀子苷大鼠经口毒性NOAEL值为50 mg/kg·bw,以雄性大鼠血清AST活性变化为敏感指标,基于此试验剂量-反应关系经BMD模型计算得出雄性大鼠的BMDL10为38.625 mg/kg·bw。不确定系数为100,推导栀子苷的每日可耐受摄入量(tolerable daily intake,TDI)为0.386 mg/kg·bw。结论栀子苷主要表现为肝毒性,尚无证据表明栀子苷具有遗传毒性,基于危害评估得出栀子苷健康指导值为每日386μg/kg·bw。Objective Hazard assessment of the health effects of geniposide was carried out on the basis of systematic literature search according to the available toxicological information,and the health-based guidance value(HBGV)of geniposide was deduced on the basis of the benchmark dose(BMD)method.Methods Using systematic literature search(SLS),geniposide toxicology data was collected,ToxRTool was utilized to evaluate the quality of the included literature,the literature was selected with the highest toxicology data rating to apply the benchmark dose method to measure the critical effect and dose,and combined with the uncertainty coefficients to derive the health guidance value of geniposide.Results Including a total of 10 geniposide toxicity literature,which toxicity study focuses on liver and kidney toxicity,after toxicological reliability evaluation,finally a 26-week rat oral toxicity test literature was selected,derived geniposide rat oral toxicity NOAEL value of 50 mg/kg·bw,change in serum AST activity in male rats was used as a sensitive indicator,and based on this test the dose-response relationship was calculated by the BMD model to give a BMDL_(10)of 38.625 mg/kg·bw in male rats.The uncertainty coefficient was 100,and the tolerable daily intake(TDI)of geniposide was 0.386 mg/kg·bw.Conclusion Geniposide show mainly hepatotoxicity,there is no evidence of genotoxicity of geniposide,based on the hazard assessment,a health guideline value for geniposide was derived as 386μg/kg·bw.

关 键 词：栀子苷 危害评估 基准剂量法 健康指导值 

分 类 号：R114[医药卫生—卫生毒理学] R285[医药卫生—公共卫生与预防医学] R99