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

PLoS One. 2016 Aug 18;11(8):e0161240. doi: 10.1371/journal.pone.0161240. eCollection 2016.

Abstract

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), β2-microglobulin (β2-MG), and N-acetyl-b-glucosaminidase (NAG) in urine were detected for analysis of BMD and BMD low (BMDL) of UCd. RBP, β2-MG, and NAG in urine all correlated significantly (P < 0.001) with UCd except of age (P = 0.767). When the benchmark response (BMR) was 5%, the BMD/BMDL of UCd for RBP, β2-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, β2-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 β2-MG and NAG were more sensitive than RBP in response to Cd exposure. But β2-MG was the most sensitive indicator in women, and NAG was the most sensitive one in men.

MeSH terms

  • Acetylglucosaminidase / urine
  • Adolescent
  • Adult
  • Aged
  • Cadmium / toxicity*
  • Cadmium / urine
  • Child
  • China
  • Creatinine / urine
  • Environmental Exposure / adverse effects
  • Environmental Exposure / statistics & numerical data
  • Female
  • Humans
  • Kidney / drug effects
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / urine
  • Male
  • Middle Aged
  • Retinol-Binding Proteins / urine
  • Sex Factors
  • Threshold Limit Values
  • Young Adult
  • beta 2-Microglobulin / urine

Substances

  • Retinol-Binding Proteins
  • beta 2-Microglobulin
  • Cadmium
  • Creatinine
  • Acetylglucosaminidase

Grants and funding

The authors acknowledge funding by the National Natural Science Foundation of China (81472960, 81001242), the Medical Scientific Research of Zhejiang Province (2009A044), the Zhejiang Provincial Natural Science (LQ14H260003), the Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents (2014), and the Zhejiang Committee of Science and Technology (2015F10013).