Pharmacokinetics/pharmacodynamics (PK/PD) modeling of risks of kidney toxicity from exposure to cadmium: Estimates of dietary risks in the US population
Pharmacokinetics/pharmacodynamics (PK/PD) modeling of risks of kidney toxicity from exposure to cadmium: Estimates of dietary risks in the US population
复制标题
DOI：
10.1080/15287390390227589
复制
发表时间：
2003-11-28
期刊：
影响因子：
--
通讯作者：
Choudhury, H
中科院分区：
文献类型：
--
作者：
Diamond, GL;Thayer, WC;Choudhury, H
对镉暴露与肾毒性之间关系的流行病学研究进行了分析。从15项不同暴露（职业、一般环境、环境污染）的研究中获得了低分子量（LMW）蛋白尿与各种镉剂量指数（膳食镉摄入量、尿镉排泄量或组织镉负荷）相关的剂量-反应函数。将与0.1、0.15或0.2的LMW蛋白尿概率对应的剂量估计值从报告的剂量单位转换为相应的靶器官剂量估计值（μ g Cd/g肾皮质，RC，通过使用药代动力学（PK）模型进行模拟。与0.1概率（RC 10 M）的低分子量蛋白尿相关的中位RC预计为153 μ g Cd/g皮质（95%置信区间[CI]：84-263）。预计在女性中1 mug/kg/d或男性中2.2 mug/kg/d的恒定慢性摄入量下可达到RC 10 M（RC 10 L，84 mug/g皮质）的置信下限。RC 10 L是2.5-5倍高于中位数RC预测导致饮食中的镉摄入量在美国非吸烟者（微克镉/克皮质：33，女性; 77，男性）和1.6-3倍高于相应的第95百分位RC（53，女性; 27，男性）。吸烟（约20支香烟/天，3 mug Cd吸入/天）的额外暴露预计会使中位RC（mug/g皮质）增加约45-70%（48，女性; 29，男性）;然而，吸烟者的预计第95百分位RCS（66，女性; 38，男性）低于RC 10 L。这些结果表明，对于大多数美国人来说，在没有其他来源的暴露的情况下，饮食来源的风险可能可以忽略不计。
An analysis of epidemiological studies of associations between exposure to cadmium and kidney toxicity was conducted. Dose-response functions relating low-molecular-weight (LMW) proteinuria to various indices of cadmium dose (dietary cadmium intake, urinary cadmium excretion, or tissue cadmium burden) were obtained from 15 studies of diverse exposures (occupational, general environmental, environmental contamination). Estimates of the dose corresponding to probabilities of LMW proteinuria of 0.1, 0.15, or 0.2 were transformed from the reported dose units into corresponding estimates of target organ dose (mug Cd/g renal cortex, RC by simulation using a pharmacokinetics (PK) model. The median RC associated with a 0.1 probability (RC10M) of LMW proteinuria was predicted to be 153 mug Cd/g cortex (95% confidence interval [CI]: 84-263). The lower confidence limit on the RC10M (RC10L, 84 mug/g cortex) was predicted to be attained with a constant chronic intake of 1 mug/kg/d in females or 2.2 mug/kg/d in males. The RC10L was 2.5-5 times higher than the median RCs predicted to result from dietary cadmium intake in U.S. nonsmokers (mug Cd/g cortex: 33, females; 77, males) and 1.6-3 times higher than the corresponding 95th percentile RCs (53, females; 27, males). Additional exposure from smoking cigarettes (approximately 20 cigarettes/d, 3 mug Cd inhaled/d) was predicted to increase the median RC (mug/g cortex) by approximately 45-70% (48, females; 29, males); however, predicted 95th percentile RCS for smokers (66, females; 38, males) were lower than the RC10L. These results indicate that, for most of the U.S. population, dietary-derived risks are likely to be negligible, in the absence of exposures from other sources.