基于贝叶斯模型平均的基准剂量估计及其在白银市人群镉暴露评估中的应用  

Benchmark dose estimation based on Bayesian model averaging and its application to evaluation of cadmium exposure of population in Baiyin

作　　者：贺娜娜 孙金芳[1] 何杰宇 余小金[1] HE Nana;SUN Jinfang;HE Jieyu;YU Xiaojin(School of Public Health,Southeast University,Nanjing,Jiangsu 210009,China;School of Public Health,Kunming Medical University,Kunming,Yunnan 650500,China)

机构地区：[1]东南大学公共卫生学院,江苏南京210009 [2]昆明医科大学公共卫生学院,云南昆明650500

出　　处：《环境与职业医学》2022年第9期1004-1010,共7页Journal of Environmental and Occupational Medicine

基　　金：国家自然科学基金面上项目(81573159);江苏省研究生科研与实践创新计划项目(SJCX20_0064);中央高校基本科研业务费专项资金(3225002110D)。

摘　　要：[背景]最优模型法估计基准剂量(BMD)时未考虑模型选择的不确定性,国内暂无使用贝叶斯模型平均(BMA)估计BMD的研究。[目的]将BMA应用于我国镉污染的暴露评估研究,讨论BMA在基于剂量-反应模型的BMD估计中的作用,为有害物质健康风险评估提供方法学支持。[方法]模拟研究基于甘肃省白银市某镉污染区数据获得的不同剂量-反应模型(Gamma、Loglogistic、Log-probit、Two-stage和Weibull模型)的参数和中国5个镉污染区的尿镉范围,模拟不同正确模型、不同剂量组数(5、8)、不同样本量(50、100、200)的模拟数据,比较BMA和最优模型法的优劣。实例分析使用甘肃省白银市某镉污染区的镉暴露数据。模拟研究和实例分析均以尿镉为镉暴露指标,β_(2)-微球蛋白异常率为效应指标,基准反应设定为10%,分别使用正确模型(模拟数据时使用的模型)、最优模型法[赤池信息准则(AIC)最小的模型]和BMA估计BMD及其95%置信区间下限(BMDL);比较不同方法估计的BMD、BMDL及相对偏差。[结果]对于模拟研究,随着样本量或剂量组数增加,BMD的第5百分位数和第90百分位数区间大致呈现变窄趋势;当正确模型为单一模型时,BMA估计的BMD相对偏差大于最优模型法;当正确模型为等权重混合模型时,BMA估计的BMD相对偏差小于最优模型法。基于实例数据,最优模型为Log-probit模型(AIC=1814.46),其次为Log-logistic模型(AIC=1814.57);Log-probit模型、Log-logistic模型和BMA估计的BMD(BMDL)分别为3.46(2.68)、3.16(2.33)和2.92(2.07)μg·g^(−1)。[结论]在正确模型已知时,最优模型法依然是值得推荐的方法;但在有害物质剂量-反应关系高度不确定或来源人群、暴露分组等不同时,BMA与最优模型法相比,理论上更充分地考虑了可能存在的多个备选模型,能提供更为稳定的BMD和BMDL估计。[Background]The optimal model method for estimation of benchmark dose(BMD)does not consider the uncertainty of model selection.There is a lack of studies on using Bayesian model averaging(BMA)to estimate BMD.[Objective]To apply BMA to the exposure assessment of cadmium pollution in China,discuss the role of BMA in estimating BMD based on dose-response models,and to provide methodological support for health risk assessment of hazardous substances.[Methods]The parameters of five dose-response models(Gamma,Log-logistic,Log-probit,Twostage,and Weibull models)estimated from the data from a cadmium-contaminated area in Baiyin City of Gansu Province and the urinary cadmium ranges in five cadmium-contaminated areas in China were used to simulate the data of varied correct models with different numbers of dosage groups(5 and 8)and different sample sizes(50,100,and 200),then the performance of BMA and traditional optimal model were compared.The case analysis used the cadmium exposure data in Baiyin,Gansu Province.All analyses set urinary cadmium as the indicator of cadmium exposure,the abnormal rate ofβ_(2)-microglobulin as the effect indicator,and the benchmark response to 10%.The correct model(the model used when simulating data),optimal model[the model with smallest Akaike information criterion(AIC)],and BMA were used to estimate BMD and lower confidence limit of benchmark dose(BMDL);the BMDs,BMDLs,and relative deviations from different methods were compared.[Results]In the simulation study,with increasing sample size or the number of dosage groups,the intervals of the 5th percentile and the 90th percentile of BMD tended to be narrower;when the correct model was a single model,the relative deviation of BMD estimation by BMA was greater than that of the traditional optimal model;when the correct model was an equal weight mixed model,the relative deviation of BMD estimation by BMA was less than that by the traditional optimal model.For the data of cadmium-contaminated areas,the optimal model was a Log-probit model(AIC=18

关 键 词：基准剂量 剂量-反应模型 贝叶斯模型平均 尿镉 暴露评估 

分 类 号：R12[医药卫生—环境卫生学]