The threshold level of urinary cadmium associated with increased urinary excretion of retinol-binding protein and β2-microglobulin: a re-assessment in a large cohort of nickel-cadmium battery workers
- Correspondence to Alfred Bernard, Unit of Toxicology and Applied Pharmacology, Catholic University of Louvain, Avenue E. Mounier 53.02, Brussels B-1200, Belgium;
- Accepted 23 June 2010
- Published Online First 8 October 2010
Objective To evaluate the threshold value of urinary cadmium (CdU) for renal dysfunction on the basis of relationships unconfounded by protein degradation, diuresis and the renal effects associated with chronic smoking.
Methods We studied 599 workers (451 men, mean age 45.4 years) who were employed in four nickel-cadmium battery plants for 18.8 years on average. After adjustment for covariates by multiple regression, the CdU threshold values for increased concentrations of retinol-binding protein (RBPU) and b2-microglobulin (b2-mU) were assessed by logistic regression and benchmark dose analyses using as referents workers with CdU<1 μg/g creatinine.
Results Relationships between urinary proteins and CdU (μg/g creatinine) were influenced by sex, age, diuresis and especially smoking. When considering all workers, odds for abnormal RBPU and b2-mU were significantly increased from CdU of 6-10 and >10, respectively. The benchmark dose (BMD5) and the benchmark dose lower limit (BMDL5) for a 5% excess in the background prevalence of abnormal RBPU and b2-mU were estimated at 5.1/3.0 and 9.6/5.9. When excluding ever smokers, odds for abnormal RBPU and b2-mU were both increased only among workers with CdU>10 (OR, 21.8, 95% CI, 6.4-74.4 and OR, 15.1, 95% CI, 3.6-63.1, respectively). In never smokers, these BMD5/BMDL5 of CdU were estimated at 12.6/6.6 and 12.2/5.5 while in ever smokers they were 6.2/4.9 and 4.3/3.5.
Conclusions On the basis of associations undistorted by smoking and adjusted for covariates, the BMDL5 of CdU for low-molecular-weight proteinuria induced by occupational exposure to Cd can be reliably estimated between 5.5 and 6.6 μg/g creatinine.
- retinol-binding protein
- benchmark dose
- biological monitoring
- risk assessment
Funding Alfred Bernard is Research Director of the National Fund for Scientific Research in Belgium. The study was supported by the Reach Cadmium Consortium and the European Union (FP6 Phime project, coordinator Staffan Skerfing). The funders of the study had no role in the data analysis, data interpretation and writing of the report.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.