Estimation of Benchmark Dose of Cumulative Cadmium Exposure for Renal Tubular Effect

Int J Environ Res Public Health. 2021 May 13;18(10):5177. doi: 10.3390/ijerph18105177.


Objectives: The aim of this study was to determine the no observed adverse effect level (NOAEL), the lowest observed adverse effect level (LOAEL) and the benchmark dose low (BMDL) of cadmium exposure by re-evaluation of the dose-response relationship between cumulative cadmium exposure and renal tubular damage reported previously.

Methods: The participants were workers (326 men and 114 women) employed for at least three months between 1931 and 1982. Blood cadmium (Cd-B) and air cadmium (Cd-A) were collected at regular intervals with urinary β2-microglobulin as the tubular effect marker. Cumulative Cd-A and Cd-B were estimated by multiplying concentration and working period. The BMDL was calculated using Benchmark Dose Software (version 3.1.2). The benchmark response (BMR) was set at 5% or 10%.

Results: By logistic regression, the NOAEL of mean cumulative Cd-B was 7122 months nmol/L. The LOAEL of cumulative Cd-A and least-squares cumulative Cd-B was 691 yrs μg/m3 and 8586 months nmol/L, respectively. Among various models for dose-response relationships, a probit model was adopted as the best fitting model. The obtained BMDLs of cumulative Cd-A were 272.3 yrs µg/m3 (BMR5%) and 707.5 yrs µg/m3 (BMR10%). The BMDLs of mean cumulative Cd-B were 3967.2 months nmol/L (BMR5%) and 7798.1 months nmol/L (BMR10%). The BMDLs of least-squares cumulative Cd-B were 3588.6 months nmol/L (BMR5%) and 8616.3 months nmol/L (BMR10%). Assuming a working period of 40 years, the BMDLs for BMR10% corresponded to 17.7 µg/m3 (Cd-A) and 1.8~2.0 µg/L (Cd-B).

Discussion: This study provides new valuable information to enhance the reliability of limit values and thereby make a significant contribution to preventing the health effects of Cd in exposed workers.

Keywords: air cadmium; benchmark dose; blood cadmium; occupational exposure.

MeSH terms

  • Benchmarking*
  • Cadmium* / toxicity
  • Environmental Exposure / analysis
  • Female
  • Humans
  • Male
  • Reproducibility of Results
  • beta 2-Microglobulin


  • beta 2-Microglobulin
  • Cadmium