title: Reassessment of the threshold of urinary cadmium by using hybrid approach in a cadmium non-polluted area in Japan.
abstract: OBJECTIVE
  We applied an updated hybrid approach to estimate the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) for cadmium-induced renal effects as the threshold of urinary cadmium in humans. Using this method, the BMD and BMDL were estimated based on continuous exposure and continuous effect marker, thereby avoiding categorization of subjects, an inevitable outcome of previously used approaches.
  
  
  METHODS
  The target subjects were 547 men and 723 women, aged 50 years or older, who lived in a cadmium non-polluted area of Japan. We measured urinary cadmium (U-Cd) as a marker of long-term exposure, and urinary protein, β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG) as renal effect markers. BMD and BMDL corresponding to an additional risk (BMR) of 5%, were calculated with the background risk at zero exposure set at 5%.
  
  
  CONCLUSIONS
  The BMDL of U-Cd for renal effect markers were 2.1 (urinary protein), 2.6 (β2-MG) and 4.1 (NAG) μg/g creatinine in men and 1.5 (urinary protein), 1.4 (β2-MG) and 3.1 (NAG) μg/g creatinine in women. The BMDLs in the present study may contribute to further discussion on health risk assessment of cadmium exposure, when compared to BMDLs obtained by previously reported methods.
authors.affiliation: Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, Chiba, 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: Teruhiko
authors.initials: T
authors.lastname: Kido
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakagawa
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D000368:Aged; D015415:Biomarkers / Q000652:urine; D002104:Cadmium / Q000652:urine*; D002105:Cadmium Poisoning / Q000175:diagnosis / Q000652:urine*; D003404:Creatinine / Q000652:urine; D004781:Environmental Exposure / Q000009:adverse effects*; D004784:Environmental Monitoring / Q000379:methods*; D004785:Environmental Pollutants / Q000652:urine*; D005260:Female; D006801:Humans; D007564:Japan; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012306:Risk; D012737:Sex Factors; D001613:beta 2-Microglobulin / Q000652:urine
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D001613:beta 2-Microglobulin; D002104:Cadmium; D003404:Creatinine; D000118:Acetylglucosaminidase