食品中交链孢酚和交链孢酚单甲醚的危害评估  

Hazard assessment of alternariol and alternariol monomethyl ether in food

作　　者：齐丽娟[1] 李国君[1,2] 宁钧宇[1,2] 张维[1] 郑珊[1] 聂燕敏[1] 高珊[1] QI Li-juan;LI Guo-jun;NING Jun-yu;ZHANG Wei;ZHENG Shan;NIE Yan-min;GAO Shan(Beijing Center for Disease Prevention and Control,Beijing Key Laboratory of Diagnostic and Tracebility Technologies for Food Poisoning,Beijing 100013,China;School of Public Health,Capital Medical University,Beijing 100069,China)

机构地区：[1]北京市疾病预防控制中心,食物中毒诊断溯源技术北京市重点实验室,北京100013 [2]首都医科大学公共卫生学院,北京100069

出　　处：《毒理学杂志》2024年第3期173-184,共12页Journal of Toxicology

基　　金：首都高层次公共卫生技术人才建设项目卫生毒理学科“领军人才”(#02-03)。

摘　　要：目的对交链孢酚(alternariol,AOH)和交链孢酚单甲醚(alternariol monomethyl ether,AME)可能对人体健康产生的有害影响进行危害评估。方法本研究采用系统文献检索方法,确定研究对象和研究内容,制定检索策略进行系统文献检索。通过NoteExpress软件进行文献查重,并通过人工筛选获得文献,纳入危害评估报告。结果AOH和AME是食品污染中常见2种链格孢毒素。其污染食品以植物性膳食为主,其中谷物的污染占主要地位。体内毒代动力学研究显示,AME大部分不被吸收,经粪便排出。胃肠道对AOH的吸收性研究结果存在差异。体外代谢研究显示,AOH和AME的I期生物转化为2-、4-、8-和10-羟基衍生物。II期生物转化为硫酸盐缀合物,其代谢产物可能具有毒理学相关性。AOH和AME动物毒性资料不充足,现有研究显示,AOH和AME具有急性毒性:AOH和AME腹腔注射DBA/2小鼠LD50值大于400 mg/kg·bw。AOH和AME已有较为明确的体外遗传毒性数据,且体内毒性研究显示AME对SD大鼠具有遗传毒性,可诱导基因突变、染色体断裂和DNA损伤。但AOH对雄性SD大鼠的体内遗传毒性不明确,可能会累积诱导遗传突变。亚急性毒性研究显示,AOH和AME可致动物肝、肾和脾受损。经口途径或经皮下注射给予小鼠AME均未显示胚胎毒性效应。但一定剂量下经皮下注射AOH或者AOH+AME(1∶1)混合物显示出胚胎毒性。AOH和AME尤其是AOH可能有类雌激素效应,通过影响黄体酮和类固醇等合成而影响哺乳动物生殖发育。体内外研究表明,长期暴露于链格孢毒素可能是诱发食管癌的危险因素。体外研究显示,AOH和AME可影响细胞活性、抑制细胞生长、抑制蛋白质合成,并诱导细胞凋亡,且两者可能具有协同毒性作用。结论EFSA专家组设定AOH和AME的毒理学关注阈值(threshold of toxicological concern,TTC)分别为2.5 ng/kg·bw/d。根据AME多终点28 d毒性试验研究结果,推导出人类Objective To evaluate the potential harmful effects of alternariol(AOH)and alternariol monom ethylether(AME)on human health.Methods The method of systematic document retrieval was used in our study.Firstly,the research object and content,formulate retrieval strategies were determined,and then enormous literature and conduct literature duplication through software were collected.Finally the literature to be included in the hazard assessment report was manually selected.Results AOH and AME are two common types of Alternaria toxins.They have been widely detected in a variety of foods.The main source of contaminated food is plant-based diets,with grains being the main source of contamination.In vivo toxicokinetic studies,it had shown that most of AME was not absorbed and was excreted through feces in rats.There were differences in the absorption study of AOH in the gastrointestinal tract,and further exploration is needed.In vitro metabolism studies,it had showed that AOH and AME were transformed into 2-,4-,8-and 10 hydroxy derivatives in Phase I biotransformation.And then,sulfate conjugates were formed in Phase II.Their metabolites may have toxicological relevance.Up to now,the animal toxicity data on AOH and AME is insufficient.It have shown that AOH and AME have acute toxicity.The LD_(50)value of AOH or AME is greater than 400 mg/kg·bw,which were administered to DBA/2 mice by intraperitoneal injection.There was clear vitro genotoxicity data about AOH and AME.It has shown that AME has genotoxicity to SD rats,which can induce gene mutation,chromosome breakage and DNA damage.However,the genotoxicity of AOH to male SD rats is not clear,and it may induce genetic mutations cumulatively,which needs further research.Subacute toxicity studies had shown that AOH and AME can cause damage to the liver,kidneys,and spleen of animals.AME did not show embryotoxic effects in DBA/2 mice by oral gavage or subcutaneous injection.However,AOH or AOH+AME mixture showed embryotoxic effects in DBA/2 mice by subcutaneous injection.AOH and

关 键 词：交链孢酚 交链孢酚单甲醚 危害评估 

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