title: Estimation of the benchmark dose of urinary cadmium as the reference level for renal dysfunction: a large sample study in five cadmium polluted areas in China.
abstract: BACKGROUND
  Itai-itai disease primarily results from cadmium (Cd) exposure and is known as one of the four major pollution diseases in Japan. Cd pollution is more serious in several areas of China than in Japan. However, there is still a lack of information regarding the threshold level of Cd exposure for the adverse health effects in the general Chinese population. This study aims to evaluate the reference value of urinary Cd (UCd) for renal dysfunction in a Chinese population as the benchmark dose lower confidence limit (BMDL) based on a large sample survey.
  
  
  METHODS
  A total of 6103 participants who lived in five Cd polluted areas of China participated in this study. We analyzed UCd levels as a biomarker of exposure and urinary β2-microglobulin (Uβ2-MG) levels as a renal tubular effect biomarker. The BMD studies were performed using BMD software. The benchmark response (BMR) was defined as a 10% additional risk above the background.
  
  
  RESULTS
  There was a positive correlation between the UCd levels and the prevalence of Uβ2-MG. The BMD of UCd for Uβ2-MG was estimated for each province. The findings showed that the BMD levels were related to the participants' geographic region, which may be partially due to the large differences in Cd exposure level, ethnic group, lifestyle and diet of the sample population in these study areas. The reference level of UCd for the renal effects was further evaluated by combining the five sets of data from all 6103 subjects. The overall BMDLs of UCd for Uβ2-MG with an excess risk of 10% were 2.00 μg/g creatinine (μg/g cr) in males and 1.69 μg/g cr in females, which were significantly lower than the World Health Organization (WHO) threshold level of 5 μg/g cr for Cd-related renal effects.
  
  
  CONCLUSIONS
  The selection of the sample population and geographic region affected the BMDL evaluation. Based on the findings of this survey of a large sample population, the UCd BMDLs for Uβ2-MG in males with BMRs at 10% were 2.00 μg/g cr. The BMD was slightly lower in females, which indicated that females may be relatively more sensitive to Cd exposure than males.
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, 100044, People's Republic of China. shke@bjtu.edu.cn.
authors.forename: Shen
authors.initials: S
authors.lastname: Ke
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, 100044, People's Republic of China. xycheng@bjtu.edu.cn.
authors.forename: Xi-Yu
authors.initials: XY
authors.lastname: Cheng
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, 100044, People's Republic of China. 13121589@bjtu.edu.cn.
authors.forename: Jie-Ying
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, 100044, People's Republic of China. 12121628@bjtu.edu.cn.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Jia
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, 100044, People's Republic of China. 12121666@bjtu.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, 100044, People's Republic of China. 4121589@bjtu.edu.cn.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Luo
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, 100044, People's Republic of China. phge1000@126.com.
authors.forename: Peng-He
authors.initials: PH
authors.lastname: Ge
authors.affiliation: State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, People's Republic of China. zmliu1000@163.com.
authors.forename: Ze-Min
authors.initials: ZM
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, People's Republic of China. hmwang1000@163.com.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Wang
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, 100044, People's Republic of China. jshhe@bjtu.edu.cn.
authors.forename: Jin-Sheng
authors.initials: JS
authors.lastname: He
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, 100044, People's Republic of China. chen_zhinan56@163.com.
authors.forename: Zhi-Nan
authors.initials: ZN
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D002104:Cadmium / Q000009:adverse effects* / Q000652:urine*; D002681:China / Q000453:epidemiology; D004781:Environmental Exposure / Q000009:adverse effects*; D004787:Environmental Pollution / Q000009:adverse effects*; D005260:Female; D015386:Hazardous Substances; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012016:Reference Values; D012044:Regression Analysis; D012306:Risk; D001613:beta 2-Microglobulin / Q000652:urine
chemical_list: D015415:Biomarkers; D015386:Hazardous Substances; D001613:beta 2-Microglobulin; D002104:Cadmium