Critical exposure level of cadmium for elevated urinary metallothionein—An occupational population study in China

Cadmium is a well-known nephrotoxic agent with extremely long biological half-time of 15–30 years in humans. To prevent nephrotoxicity induced by cadmium, it is necessary to identify specific and sensitive biomarkers of cadmium exposure and renal damage, and to define critical exposure levels related to minimal nephrotoxicity in humans. In this study, urinary cadmium (UCd) and blood cadmium (BCd) were used as cadmium exposure indicators, urinary β2-microglobulin (UB2M), N-acetyl-β-d-glucosaminidase (UNAG) and albumin (UALB) were applied as the effect biomarkers of tubular and glomerular dysfunction. The relationship between urinary metallothionein (UMT) and cadmium exposure biomarkers as well as effect biomarkers was examined. Significant correlations were found between the UMT and BCd, and UCd. At the same time, UB2M, UALB and UNAG showed positive correlation with UMT as well. According to this result, cadmium-exposed individuals with renal dysfunction excreted more metallothionein than those without. Dose–response relationships between UCd and urinary indicators of renal dysfunction were studied. The critical concentration of UCd was quantitatively estimated by the benchmark dose (BMD) method. The lower confidence limit of the BMD-10 (BMDL) of UCd (3.1 μg/g Cr) related to increased excretion of urinary metallothionein was slightly higher than that for UNAG (2.7 μg/g Cr), but lower than those of UB2M (3.4 μg/g Cr) and UALB (4.2 μg/g Cr). The results demonstrate that UMT may be used as a sensitive biomarker of renal tubular dysfunction in cadmium-exposed populations.