Journal Article

The Reference Dose for Subchronic Exposure of Pigs to Cadmium Leading to Early Renal Damage by Benchmark Dose Method

Xiaosheng Wu, Shuai Wei, Yimin Wei, Boli Guo, Mingqi Yang, Duoyong Zhao, Xiaoling Liu and Xianfeng Cai

in Toxicological Sciences

Volume 128, issue 2, pages 524-531
Published in print August 2012 | ISSN: 1096-6080
Published online May 2012 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfs173
The Reference Dose for Subchronic Exposure of Pigs to Cadmium Leading to Early Renal Damage by Benchmark Dose Method

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Pigs were exposed to cadmium (Cd) (in the form of CdCl2) concentrations ranging from 0 to 32mg Cd/kg feed for 100 days. Urinary cadmium (U-Cd) and blood cadmium (B-Cd) levels were determined as indicators of Cd exposure. Urinary levels of β2-microglobulin (β2-MG), α1-microglobulin (α1-MG), N-acetyl-β-D-glucosaminidase (NAG), cadmium-metallothionein (Cd-MT), and retinol binding protein (RBP) were determined as biomarkers of tubular dysfunction. U-Cd concentrations were increased linearly with time and dose, whereas B-Cd reached two peaks at 40 days and 100 days in the group exposed to 32mg Cd/kg. Hyper-metallothionein-urinary (HyperMTuria) and hyper-N-acetyl-β-D-glucosaminidase-urinary (hyperNAGuria) emerged from 80 days onwards in the group exposed to 32mg Cd/kg feed, followed by hyper-β2-microglobulin-urinary (hyperβ2-MGuria) and hyper-retinol-binding-protein-urinary (hyperRBPuria) from 100 days onwards. The relationships between the Cd exposure dose and biomarkers of exposure (as well as the biomarkers of effect) were examined, and significant correlations were found between them (except for α1-MG). Dose–response relationships between Cd exposure dose and biomarkers of tubular dysfunction were studied. The critical concentration of Cd exposure dose was calculated by the benchmark dose (BMD) method. The BMD10/BMDL10 was estimated to be 1.34/0.67, 1.21/0.88, 2.75/1.00, and 3.73/3.08mg Cd/kg feed based on urinary RBP, NAG, Cd-MT, and β2-MG, respectively. The calculated tolerable weekly intake of Cd for humans was 1.4 μg/kg body weight based on a safety factor of 100. This value is lower than the currently available values set by several different countries. This indicates a need for further studies on the effects of Cd and a re-evaluation of the human health risk assessment for the metal.

Keywords: cadmium; renal dysfunction; biomarkers; benchmark dose; subchronic exposure

Journal Article.  5340 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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