Application of the Benchmark Dose (BMD) Method to Identify Thresholds of Cadmium-Induced Renal Effects in Non-Polluted Areas in China

<div><p>The benchmark dose (BMD) method has been increasingly used to assess the health risks of cadmium (Cd) in epidemiological studies. The aim of our study was to estimate the threshold levels of urinary Cd (UCd) using the BMD method in a general population of Jiangshan City, Zhejiang Province of China. In our study, a total of 934 people (469 men, 465 women) were recruited and morning urine samples were collected from all the participants. Levels of Cd, creatinine, and renal dysfunction indicators such as retinol binding protein (RBP), <i>β</i>2-microglobulin (<i>β</i>2-MG), and N-acetyl-<i>b</i>-glucosaminidase (NAG) in urine were detected for analysis of BMD and BMD low (BMDL) of UCd. RBP, <i>β2</i>-MG, and NAG in urine all correlated significantly (<i>P</i> < 0.001) with UCd except of age (<i>P</i> = 0.767). When the benchmark response (BMR) was 5%, the BMD/BMDL of UCd for RBP, <i>β</i>2-MG, and NAG was 1.69/ 0.89, 1.24/0.62, 0.85/0.49 μg/g Cr in men and 1.70/0.76, 1.35/0.64, 1.36/0.65 μg/g Cr in women, respectively. If the BMR was set at 10%, the BMD/BMDL of UCd for RBP, <i>β</i>2-MG, and NAG was 2.44/1.59, 2.09/1.30, 1.80/1.04 μg/g Cr in men and 2.43/1.53, 2.10/1.34, 2.31/1.37 μg/g Cr in women, respectively. Our results provided evidence for Cd-induced tubular effects in cadmium non-polluted areas in China. Both <i>β</i>2-MG and NAG were more sensitive than RBP in response to Cd exposure. But <i>β</i>2-MG was the most sensitive indicator in women, and NAG was the most sensitive one in men.</p>