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

文献类型： 外文期刊

第一作者： Wu, Xiaosheng

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

作者机构：

关键词： cadmium;renal dysfunction;biomarkers;benchmark dose;subchronic exposure

期刊名称：TOXICOLOGICAL SCIENCES （ 影响因子：4.849； 五年影响因子：4.996 ）

ISSN： 1096-6080

年卷期： 2012 年 128 卷 2 期

页码：

收录情况： SCI

摘要： Pigs were exposed to cadmium (Cd) (in the form of CdCl2) concentrations ranging from 0 to 32 mg 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 beta(2)-microglobulin (beta(2)-MG), alpha(1)-microglobulin (alpha(1)-MG), N-acetyl-beta-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 32 mg Cd/kg. Hyper-metallothionein-urinary (HyperMTuria) and hyper-N-acetyl-beta-D-glucosaminidase-urinary (hyperNA-Guria) emerged from 80 days onwards in the group exposed to 32 mg Cd/kg feed, followed by hyper-beta 2-microglobulin-urinary (hyper beta 2-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 alpha(1)-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 beta(2)-MG, respectively. The calculated tolerable weekly intake of Cd for humans was 1.4 mu g/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.

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