title: The reference dose for subchronic exposure of pigs to cadmium leading to early renal damage by benchmark dose method.
abstract: Pigs were exposed to cadmium (Cd) (in the form of CdCl(2)) 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 β(2)-microglobulin (β(2)-MG), α(1)-microglobulin (α(1)-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 α(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 BMD(10)/BMDL(10) 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 β(2)-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.
authors.affiliation: Institute of Agro-Products Processing Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-Products Processing, Ministry of Agriculture,P.O. Box 5109 Beijing 100193 China.
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: Wu
authors.forename: Shuai
authors.initials: S
authors.lastname: Wei
authors.forename: Yimin
authors.initials: Y
authors.lastname: Wei
authors.forename: Boli
authors.initials: B
authors.lastname: Guo
authors.forename: Mingqi
authors.initials: M
authors.lastname: Yang
authors.forename: Duoyong
authors.initials: D
authors.lastname: Zhao
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Liu
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Cai
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D000510:Alpha-Globulins / Q000652:urine; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D012177:Retinol-Binding Proteins / Q000652:urine; D013552:Swine; D001613:beta 2-Microglobulin / Q000652:urine
chemical_list: D000510:Alpha-Globulins; D012177:Retinol-Binding Proteins; C016001:alpha-1-microglobulin; D001613:beta 2-Microglobulin; D002104:Cadmium; D000118:Acetylglucosaminidase