title: Application of the hybrid approach to the benchmark dose of urinary cadmium as the reference level for renal effects in cadmium polluted and non-polluted areas in Japan.
abstract: OBJECTIVE
  The aim of this study was to evaluate the reference level of urinary cadmium (Cd) that caused renal effects. An updated hybrid approach was used to estimate the benchmark doses (BMDs) and their 95% lower confidence limits (BMDL) in subjects with a wide range of exposure to Cd.
  
  
  METHODS
  The total number of subjects was 1509 (650 men and 859 women) in non-polluted areas and 3103 (1397 men and 1706 women) in the environmentally exposed Kakehashi river basin. We measured urinary cadmium (U-Cd) as a marker of long-term exposure, and β2-microglobulin (β2-MG) as a marker of renal effects. The BMD and BMDL that corresponded to an additional risk (BMR) of 5% were calculated with background risk at zero exposure set at 5%.
  
  
  RESULTS
  The U-Cd BMDL for β2-MG was 3.5μg/g creatinine in men and 3.7 μg/g creatinine in women.
  
  
  CONCLUSIONS
  The BMDL values for a wide range of U-Cd were generally within the range of values measured in non-polluted areas in Japan. This indicated that the hybrid approach is a robust method for different ranges of cadmium exposure. The present results may contribute further to recent discussions on health risk assessment of Cd exposure.
authors.affiliation: Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoku, Chiba 260-8670, Japan. suwa@faculty.chiba-u.jp
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Suwazono
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nogawa
authors.forename: Mirei
authors.initials: M
authors.lastname: Uetani
authors.forename: Satoru
authors.initials: S
authors.lastname: Nakada
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Kido
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakagawa
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000652:urine; D002104:Cadmium / Q000592:standards / Q000633:toxicity / Q000652:urine*; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000032:analysis / Q000592:standards* / Q000706:statistics & numerical data; D004785:Environmental Pollutants / Q000592:standards / Q000633:toxicity / Q000652:urine*; D004787:Environmental Pollution / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007564:Japan; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D012015:Reference Standards
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D002104:Cadmium; D003404:Creatinine