【作者】 马易怡；

【导师】 郭红卫；

【作者基本信息】 复旦大学 ， 营养与食品卫生学， 2008， 硕士

【摘要】 目的:研究分析脱氧雪腐镰刀菌烯醇(DON)引起的毒性效应,估计DON毒性的NOAEL值,了解上海市城市居民DON的膳食摄入量,探讨DON的TDI值,评价上海市城市居民膳食摄入DON的安全性,为DON的危险性管理以及危险性信息交流提出意见以及建议。方法:采用系统综述及有序多分类回归模型方法确定DON的毒性效应及相应的NOAEL值。并且于2005年第2季度至2007年第2季度,分季度采集食品样品450件,经过酶联免疫方法及毛细气相色谱法检测DON在食品中的浓度,分别结合2002年度全国及上海市居民营养与健康状况调查报告资料,以及对上海市某社区564例成年居民进行的膳食调查资料,采用点估计法及概率分析法进行上海市城市居民DON的暴露估计。根据DON的NOAEL值及不确定系数,得出DON的TDI值,评价上海市城市居民膳食摄入DON的安全性。结果:①危害识别:DON属于B族单端孢霉烯族化合物,其主要的毒性结构为C12,13-环氧结构。DON的理化特性比较稳定,有一定的耐热、耐酸性。DON的主要产生菌种为禾谷镰刀菌,气候(主要是温度及湿度)是其主要的产毒条件。且各种食品加工(清洗、辗磨、挤压、酿酒)对DON的解毒作用不大。DON主要是通过胃肠道进入人体。猪是最敏感的动物。DON的主要代谢物为去环氧DON,主要经尿液排出。DON的急性毒性主要包括腹泻、呕吐、出血、循环性休克以及死亡。DON的慢性毒性主要有厌食、体重减轻、饲料效价降低、神经内分泌变化、免疫毒性等。目前的研究结果不足以证实DON是致癌物。②危害特征描述:选取与人类暴露途径相同的慢性动物实验,进行毒性终点的分类及归纳。经过有序多分类回归模型拟合,有四个毒性终点拟合成功,即血清IgA升高、体重减轻、肝胃心及淋巴器官重量减轻。以DON引起体重减轻、肝胃心及淋巴器官重量减轻为临界效应,经过模型回归,得到其NOAEL值为32.78ug/kgbw·day。③暴露评估:DON高污染的食物品种主要是玉米及面粉。梅雨季节DON的污染率高于非梅雨季节。2005～2007年上海市城市居民DON的膳食暴露量的平均水平为0.03ug/kgbw·day,其第97.5个百分点为0.15 ug/kgbw·day。根据不同性别年龄人群的DON暴露量资料显示,幼儿为高危人群。④危险性描述:以32.78 ug/kgbw·day为NOAEL值,25为不确定系数,得出DON的TDI值为1.3 ug/kgbw·day。经过与上海市城市居民的暴露资料比较,无论是总人群还是高危人群的DON膳食摄入量都低于TDI值,提示目前上海市城市居民的DON膳食摄入是安全的。但是由于暴露评估显示近两年的DON污染情况呈现上升趋势,所以仍应加强对DON污染的预防及监测工作。减少DON污染的主要工作是预防。收割前应注意选择具有抵抗力的品种、具备良好的农业操作,注意开花时的气候条件、选择合适型号及用量的抗霉菌剂、控制收割时的湿度。收割后的因素主要包括及时有效的谷粒干燥、有足够的储存空间、储存阶段的卫生清洁及管理工作。在DON的危险性评估的每一步都不可避免地包含了特定的不确定因素。并且由于资料有限,本次研究没有涉及DON的急性危险性评估,没有探讨特殊人群(孕妇、老年人等)的DON评估,没有涵盖单端孢霉烯族化合物混合污染及DON经呼吸道摄入的相关评估。结论:2005～2007年上海市城市居民的膳食DON摄入量是安全的。但是,由于DON的污染率呈上升趋势,所以仍然需要对DON污染进行监控。更多还原

【Abstract】 Objective:To investigate the toxicity of deoxynivalenol(DON),estimate the NOAEL.To know the status of dietary intake of DON by Shanghai urban residents,compute the TDI.Finally,to evaluate the safety of the dietary intake of DON by Shanghai urban residents.Methods:Systematic review method and ordinal multi-categorical regression model method were used to investigate the toxicity effects of DON and to get the NOAEL.In addition,during the summer from 2005 to 2007,the total 450 pieces of food samples were collected each season,and the ELISA method and capillary gas chromatography method were used to detect the content of DON.Point estimate method and probability analysis method were used to assess the exposure of dietary intake of DON by Shanghai urban adult residents,with the data on the 2002 report of the nutrition and health status of residents in China and Shanghai,and the dietary questionnaires of 564 residents in Shanghai.The TDI of DON was calculated out by dividing the NOAEL with the uncertainty factor,and was used to evaluate the safety of dietary intake of DON by Shanghai urban residents.Results:①Hazard identification:DON belongs to the B type of trichothecene and the main structure of toxicity is the C12,13-epoxy.It has stable chemical properties and it is resistant to heat and acid.DON is mainly produced by Fusarium graminearum.Climate(mainly temperature and humidity) is the key point of the production of DON.Different processes of food (cleaning,milling,extrusion and brewing) have no influences on detoxification of DON.DON enters human body mainly through gastrointestinal tract.Pig is the most sensitive animal.The main metabolite of DON is the de-epoxy-DON,which is excreted mainly by urine.The syndrome of acute toxicity includes diarrhea,vomiting. hemorrhage,circular shock and death.The chronic toxicity includes anorexia,decreased body weight,decreased feed conversion efficiency, neuroendocrine changes,immunotoxicity and etc.Researches are not sufficient to confirm the carcinogenicity of DON.②Hazard characterization:The chronic animal studies with the same exposure paths to human beings are selected out.All the endpoints of these studies are classified and summarized.Four endpoints could be successfully fitted to the ordinal multi-categorical model,including increased serum IgA level,decreased body weight,decreased common organs’ weight, and decreased immune organs’ weight.Then the critical effect is defined to be the property of DON causing decreased body and organs’ weight, and the NOAEL is 32.78 ug/kgbw·day.③Exposure assessment:Maize and flour are the main food with high contamination of DON.The contamination condition is more serious in raining seasons.During 2005 to 2007,the average dietary intake of DON of Shanghai urban residents is 0.03 ug/kgbw·day,and the 97.5%level is 0.15 ug/kgbw·day.The results from the analysis of the dietary intake of people with different sexes and ages show that the young children are those with the high exposure to DON.④Risk characterization:The NOAEL is 32.78 ug/kgbw·day,and the uncertainty is 25.Then the TDI is calculated out to be 1.3 ug/kgbw·day.Comparing with this TDI,the daily dietary intake of DON of Shanghai urban residents is lower than it,both in the common people and in those with high risk,which suggests that the dietary intake of DON is safe for Shanghai urban residents.However,the contamination level of DON is increasing during these years,so it is necessary to strengthen the prevention and surveillance of DON.Prevention is the key to control the contamination of DON.Before harvest,it is very important to select the right resistant wheat strains,to follow the good agronomical practice,to pay more attention to the climate during the anthesis period, to select the suitable type and amount of the anti-mold agent,and to control the humidity during the harvest.After harvest,one should pay attention to sufficient storage capacity,hygiene condition during the storage,and the good management during the short to middle term stages of storage. It is unavoidable to have some specific uncertainties in each stage of the risk assessment of DON.Due to the lack of the related studies,the risk assessment of the acute risk of DON,the risk of DON in specific kinds of people(pregnant women,the old,and etc.),and the assessment of the combined risk of DON with other trichothecenes,and the respiratory exposure of DON are ignored.Conclusion:The dietary intake of DON by Shanghai urban residents during 2005 to 2007 is safe.However,because it is also shown that the contamination of DON is increasing these years,the surveillance of DON contamination should be still in work.更多还原