Lei Li-Jian, Chen Liang, Jin Tai-Yi, Nordberg Monica, Chang Xiu-Li
Department of Occupational Health, School of Public Health, Fudan University, Shanghai 200032, China.
Toxicol Sci. 2007 May;97(1):189-95. doi: 10.1093/toxsci/kfm016. Epub 2007 Feb 14.
The aim of this study was to estimate the benchmark dose (BMD) for pancreas dysfunction caused by cadmium (Cd) exposure in smelters. Smelter workers who had been exposed to Cd for more than 1 year and matching nonoccupationally exposed subjects were asked to participate in this study. Urinary cadmium (UCd) was used as a biomarker for exposure, serum insulin and amylase were used as biomarkers for pancreatic effects. In this study, serum insulin and amylase were lower in the smelter workers than in the nonoccupationally exposed subjects. A significant dose-response relationship with UCd was displayed. BMDs in terms of urinary Cd corrected for creatinine were calculated by use of BMDS (version 1.3.2). The benchmark dose lower limit of a one-sided 95% confidence interval (BMDL) for 10% excess risk was also determined. It was found that the BMDL10 for serum insulin and serum amylase was 3.7 and 5.3 microg/g Cr, respectively. Compared to the BMDL for renal damage caused by Cd exposure, identified by the effect biomarkers urinary beta2-microglobulin, urinary N-acetyl-beta-glucosaminidase, and urinary albumin (UALB), it was shown that BMDL10 for serum insulin is the lowest among all values and UALB gave the highest value (5.8 microg/g Cr). This study indicates that Cd exposure can result in pancreatic dysfunction and the effect appears at lower urinary Cd level than renal dysfunction. The endocrine function of the pancreas was affected at lower urinary levels of Cd, compared to the exocrine function, which was seen at higher urinary levels of Cd than those giving rise to renal tubular dysfunction.
本研究的目的是估算冶炼厂镉(Cd)暴露所致胰腺功能障碍的基准剂量(BMD)。邀请了接触镉超过1年的冶炼厂工人以及相匹配的非职业性接触对象参与本研究。尿镉(UCd)用作暴露生物标志物,血清胰岛素和淀粉酶用作胰腺效应生物标志物。在本研究中,冶炼厂工人的血清胰岛素和淀粉酶水平低于非职业性接触对象。呈现出与UCd显著的剂量-反应关系。使用BMDS(版本1.3.2)计算经肌酐校正的尿镉的BMD。还确定了10%超额风险的单侧95%置信区间的基准剂量下限(BMDL)。结果发现,血清胰岛素和血清淀粉酶的BMDL10分别为3.7和5.3μg/g肌酐。与通过效应生物标志物尿β2-微球蛋白、尿N-乙酰-β-氨基葡萄糖苷酶和尿白蛋白(UALB)确定的镉暴露所致肾损伤的BMDL相比,结果显示血清胰岛素的BMDL10在所有值中最低,而UALB的值最高(5.8μg/g肌酐)。本研究表明,镉暴露可导致胰腺功能障碍,且该效应出现在低于肾功能障碍的尿镉水平时。与外分泌功能相比,胰腺的内分泌功能在较低的尿镉水平时就受到影响,外分泌功能在高于导致肾小管功能障碍的尿镉水平时才出现。