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基准剂量限值分析估计镉容许蓄积量的有效性。

The Validity of Benchmark Dose Limit Analysis for Estimating Permissible Accumulation of Cadmium.

机构信息

Kidney Disease Research Collaborative, Translational Research Institute, Brisbane 4102, Australia.

Department of Nephrology, Princess Alexandra Hospital, Brisbane 4102, Australia.

出版信息

Int J Environ Res Public Health. 2022 Nov 25;19(23):15697. doi: 10.3390/ijerph192315697.

Abstract

Cadmium (Cd) is a toxic metal pollutant that accumulates, especially in the proximal tubular epithelial cells of kidneys, where it causes tubular cell injury, cell death and a reduction in glomerular filtration rate (GFR). Diet is the main Cd exposure source in non-occupationally exposed and non-smoking populations. The present study aimed to evaluate the reliability of a tolerable Cd intake of 0.83 μg/kg body weight/day, and its corresponding toxicity threshold level of 5.24 μg/g creatinine. The PROAST software was used to calculate the lower 95% confidence bound of the benchmark dose (BMDL) values of Cd excretion (E) associated with injury to kidney tubular cells, a defective tubular reabsorption of filtered proteins, and a reduction in the estimated GFR (eGFR). Data were from 289 males and 445 females, mean age of 48.1 years of which 42.8% were smokers, while 31.7% had hypertension, and 9% had chronic kidney disease (CKD). The BMDL value of E associated with kidney tubular cell injury was 0.67 ng/L of filtrate in both men and women. Therefore, an environmental Cd exposure producing E of 0.67 ng/L filtrate could be considered as Cd accumulation levels below which renal effects are likely to be negligible. A reduction in eGFR and CKD may follow when E rises from 0.67 to 1 ng/L of filtrate. These adverse health effects occur at the body burdens lower than those associated with E of 5.24 µg/g creatinine, thereby arguing that current health-guiding values do not provide a sufficient health protection.

摘要

镉 (Cd) 是一种有毒的金属污染物,尤其在肾脏近端肾小管上皮细胞中积累,导致肾小管细胞损伤、细胞死亡和肾小球滤过率 (GFR) 降低。饮食是职业暴露和不吸烟人群中镉暴露的主要来源。本研究旨在评估 0.83μg/kg 体重/天的可耐受镉摄入量的可靠性,以及其相应的毒性阈值 5.24μg/g 肌酐。使用 PROAST 软件计算与肾小管细胞损伤、滤过蛋白肾小管重吸收缺陷和估计肾小球滤过率 (eGFR) 降低相关的镉排泄 (E) 的基准剂量 (BMDL) 值的下限 95%置信区间。数据来自 289 名男性和 445 名女性,平均年龄为 48.1 岁,其中 42.8%为吸烟者,31.7%患有高血压,9%患有慢性肾脏病 (CKD)。男性和女性与肾小管细胞损伤相关的 E 的 BMDL 值均为 0.67ng/L 滤液。因此,环境镉暴露导致 E 为 0.67ng/L 滤液时,可能被认为是肾效应可能微不足道的镉积累水平。当 E 从 0.67ng/L 滤液上升到 1ng/L 滤液时,eGFR 降低和 CKD 可能会随之发生。这些不良健康影响发生在低于与 E 为 5.24μg/g 肌酐相关的身体负荷水平,这表明当前的健康指导值不能提供充分的健康保护。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9415/9736539/1714f6aedb90/ijerph-19-15697-g001.jpg

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