Estimation of benchmark dose as the threshold levels of urinary cadmium, based on excretion of total protein, beta2-microglobulin, and N-acetyl-beta-D-glucosaminidase in cadmium nonpolluted regions in Japan

Environ Res. 2006 Jul;101(3):401-6. doi: 10.1016/j.envres.2005.12.002. Epub 2006 Jan 24.


Previously, we investigated the association between urinary cadmium (Cd) concentration and indicators of renal dysfunction, including total protein, beta2-microglobulin (beta2-MG), and N-acetyl-beta-D-glucosaminidase (NAG). In 2778 inhabitants 50 years of age (1114 men, 1664 women) in three different Cd nonpolluted areas in Japan, we showed that a dose-response relationship existed between renal effects and Cd exposure in the general environment without any known Cd pollution. However, we could not estimate the threshold levels of urinary Cd at that time. In the present study, we estimated the threshold levels of urinary Cd as the benchmark dose low (BMDL) using the benchmark dose (BMD) approach. Urinary Cd excretion was divided into 10 categories, and an abnormality rate was calculated for each. Cut-off values for urinary substances were defined as corresponding to the 84% and 95% upper limit values of the target population who have not smoked. Then we calculated the BMD and BMDL using a log-logistic model. The values of BMD and BMDL for all urinary substances could be calculated. The BMDL for the 84% cut-off value of beta2-MG, setting an abnormal value at 5%, was 2.4 microg/g creatinine (cr) in men and 3.3 microg/g cr in women. In conclusion, the present study demonstrated that the threshold level of urinary Cd could be estimated in people living in the general environment without any known Cd-pollution in Japan, and the value was inferred to be almost the same as that in Belgium, Sweden, and China.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosaminidase / urine
  • Aged
  • Aged, 80 and over
  • Benchmarking
  • Biomarkers / urine
  • Cadmium / toxicity*
  • Cadmium / urine*
  • Creatinine / urine
  • Dose-Response Relationship, Drug
  • Environmental Exposure / adverse effects*
  • Environmental Pollutants / toxicity*
  • Female
  • Humans
  • Japan
  • Kidney / drug effects
  • Kidney / physiology*
  • Kidney Function Tests
  • Logistic Models
  • Male
  • Middle Aged
  • Proteinuria / urine
  • Reference Standards
  • Renal Insufficiency / chemically induced
  • Sex Factors
  • beta 2-Microglobulin / urine


  • Biomarkers
  • Environmental Pollutants
  • beta 2-Microglobulin
  • Cadmium
  • Creatinine
  • Acetylglucosaminidase