Abstract：
Urinary cadmium (U-Cd) values are indicators for determining chronic cadmium toxicity, and previous studies have calculated U-Cd indicators using renal injury biomarkers. However, most of these studies have been conducted in adult populations, and there is a lack of research on U-Cd thresholds in preschool children. We aimed to apply benchmark dose (BMD) analysis to estimate the U-Cd threshold level associated with renal impairment in preschool children in the cadmium-polluted area. 518 preschool children aged 3-5 years were selected by systematic sampling (275 boys, 243 girls). Urinary cadmium and three biomarkers of early renal injury (urinary N-acetyl-β-D-glucosaminidase, UNAG; urinary β2-microglobulin, Uβ2-MG; urinary retinol-binding protein, URBP) were determined. Bayesian model averaging estimated the BMD and lower confidence interval limit (BMDL) of U-Cd. The medians U-Cd levels in both boys and girls exceeded the recommended national standard threshold (5 μg/g cr) and U-Cd levels were higher in girls than in boys. Urinary N-acetyl-β-D-glucosaminidase (UNAG) was the most sensitive biomarker of renal effects in preschool children. The overall BMDL5 (BMDL at a benchmark response value of 5) was 2.76 μg/g cr. In the gender analysis, the BMDL5 values were 1.92 μg/g cr for boys and 4.12 μg/g cr for girls. This study shows that the U-Cd threshold (BMDL5) is lower than the national standard (5 μg/g cr) and boys\' BMDL5 was lower than the limit set by the European Parliament and Council in 2019 (2 μg/g cr), which provides a reference point for making U-Cd thresholds for preschool children.
摘要：
尿镉（U-Cd）值是确定慢性镉毒性的指标，和以前的研究已经使用肾损伤生物标志物计算U-Cd指标。然而,这些研究大多是在成人人群中进行的，缺乏对学龄前儿童U-Cd阈值的研究。我们旨在应用基准剂量（BMD）分析来估计镉污染地区学龄前儿童与肾脏损害相关的U-Cd阈值水平。通过系统抽样选择518名3-5岁学龄前儿童(275名男孩，243名女孩)。尿镉和早期肾损伤的三种生物标志物（尿N-乙酰-β-D-氨基葡萄糖苷酶，UNAG;尿β2-微球蛋白,Uβ2-MG;尿视黄醇结合蛋白,URBP)被确定。贝叶斯模型平均估计了U-Cd的BMD和置信区间下限(BMDL)。男孩和女孩的中位数U-Cd水平均超过建议的国家标准阈值（5μg/gcr），女孩的U-Cd水平高于男孩。尿N-乙酰-β-D-氨基葡萄糖苷酶（UNAG）是学龄前儿童肾脏影响最敏感的生物标志物。总体BMDL5(基准响应值为5的BMDL)为2.76μg/gcr。在性别分析中，男孩的BMDL5值为1.92μg/gcr，女孩为4.12μg/gcr。这项研究表明，U-Cd阈值（BMDL5）低于国家标准（5μg/gcr），男孩BMDL5低于欧洲议会和理事会在2019年设定的限值（2μg/gcr），这为学龄前儿童U-Cd阈值的制定提供了参考。
