基准剂量法推导3-氯丙醇及其酯的肾小管增生效应的BMDL值  

Deduction of BMDL of 3-MCPD and its esters for renal tubular hyperplasia effect based on BMD method

作　　者：唐语 曹佩 李国君[3] 宁钧宇[3] 陈锦瑶[1] 张磊 张立实[1] 周萍萍 TANG Yu;CAO Pei;LI Guojun;NING Junyu;CHEN Jinyao;ZHANG Lei;ZHANG Lishi;ZHOU Pingping(Department of Nutrition and Food Hygiene,West China School of Public Health/West China Fourth Hospital,Sichuan University,Sichuan Chengdu 610041,China;China National Center for Food Safety Risk Assessment/NHC Key Laboratory of Food Safety Risk Assessment,Beijing 100022,China;Beijing Center for Disease Prevention and Control,Beijing 100013,China)

机构地区：[1]四川大学华西公共卫生学院/四川大学华西第四医院营养与食品卫生学系,四川成都610041 [2]国家食品安全风险评估中心/国家卫生健康委员会食品安全风险评估重点实验室,北京100022 [3]北京市疾病预防控制中心,北京100013

出　　处：《中国食品卫生杂志》2022年第5期907-915,共9页Chinese Journal of Food Hygiene

基　　金：国家重点研发计划(2018YFC1603605)。

摘　　要：目的 基于基准剂量(BMD)法推导3-氯丙醇及其酯的肾小管增生效应的基准剂量95%置信区间下限(BMDL10)。方法 利用3-氯丙醇的2年慢性毒性合并致癌性研究分析最敏感毒性终点肾小管增生,分别使用频率论模型法、频率论模型均衡法和贝叶斯模型均衡法进行BMD建模,通过对9个常规模型的拟合,获得平滑的剂量反应曲线,得到最佳拟合模型和BMDL10值。结果 通过比较不同数据集的结果保守程度,选择最佳数据集。在相同数据集的情况下,模型参数限制与不限制、单一模型与模型均衡的选择是影响3-氯丙醇及其酯的BMDL结果的重要影响因素,通过综合拟合与保守程度,3-氯丙醇及其酯的肾小管增生效应的BMDL_(10)为0.87 mg/kg·BW,此结果还需结合不确定性系数进一步确定健康指导值。结论 研究结果将为我国重点食品中3-氯丙醇及其酯的风险评估服务,根据评估结果,进一步对重点食品的监管和管控提供科学建议。Objective To calculate the lower limit of 95% confidence interval of benchmark dose(BMDL) of 3-monochloro-1,2-propanediol(3-MCPD) and its esters for renal tubular hyperplasia effect based on benchmark dose(BMD)method.Methods The data of the most sensitive endpoint of renal tubular hyperplasia in the 2-year chronic toxicity and carcinogenicity study of 3-MCPD were analyzed. BMD model and analysis were used by methods of frequentist,frequentist model averaging and Bayesian model averaging,respectively. Smooth dose response curve was obtained by fitting the nine conventional models,and then the optimal fitting model and BMDL10estimation value were obtained.Results The best data set was selected by comparing the conservative degree of results across different data sets. Under the same data set,the selection of restricted or non-restricted model parameters,and the selection of single model or model averaging,were key factors to affect the BMDL results of 3-MCPD and its esters. According to model fitting degree and conservative degree,BMDL_(10) of the most sensitive endpoint of renal tubular hyperplasia of 3-MCPD and its esters was 0. 87 mg/kg·BW. The health based guidance value(HBGV)needs to be further determined by the BMDL10with uncertainty factor.ConclusionThe results of this research could be applied for the risk assessment of 3-MCPD and its esters in key foods of China,and further provide scientific advice on the supervision and control of key foods based on the assessment results.

关 键 词：3-氯丙醇酯 基准剂量法 贝叶斯模型均衡 

分 类 号：R155[医药卫生—营养与食品卫生学]