Hayashi Takuya, Nogawa Kazuhiro, Watanabe Yuuka, Kido Teruhiko, Sakurai Masaru, Nakagawa Hideaki, Suwazono Yasushi
Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, Chiba 2608670, Japan.
Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, Kanazawa 9200942, Japan.
Toxics. 2024 Nov 21;12(12):836. doi: 10.3390/toxics12120836.
The aim of the present study was to apply an updated benchmark dose (BMD) approach to estimate reference urinary cadmium (U-Cd) for renal tubular and glomerular effects. This cross-sectional survey was conducted 30 years ago in 30 men and 44 women living in a Cd-polluted area and in 18 men and 18 women living in a non-polluted area. We applied an updated hybrid approach to estimate the BMDs and 95% lower confidence limits (BMDLs) of U-Cd for creatinine (Cr) clearance (CrCl), estimated glomerular filtration rate (eGFR), β2-microglobulin (β2-MG), and β2-MG tubular reabsorption (%TRβ2-MG). Using a benchmark response (BMR) of 5%, we estimated the BMDLs of U-Cd for adverse renal effect markers to be 2.9 (eGFR), 1.8 (β2-MG), 1.8 (%TRβ2-MG < 95%), and 3.6 μg/g Cr (%TRβ2-MG < 90%) in men, and 3.5 (CrCl), 2.5 (β2-MG), 2.6 (%TRβ2-MG < 95%), and 3.9 μg/g Cr (%TRβ2-MG < 90%) in women. The obtained BMDLs for tubular effects were 1.8-3.6 µg/g Cr and for glomerular effects were 2.9-3.5 µg/g Cr; these are not very high compared to the exposure levels in the general population. The BMDLs calculated in this study provide important information for measures regarding protecting general inhabitants or workers from the adverse health effects of Cd exposure.
本研究的目的是应用更新后的基准剂量（BMD）方法来估计肾小管和肾小球效应的参考尿镉（U-Cd）水平。这项横断面调查于30年前在生活于镉污染地区的30名男性和44名女性以及生活于非污染地区的18名男性和18名女性中进行。我们应用更新后的混合方法来估计U-Cd对于肌酐（Cr）清除率（CrCl）、估计肾小球滤过率（eGFR）、β2-微球蛋白（β2-MG）以及β2-MG肾小管重吸收（%TRβ2-MG）的BMD和95%下限置信区间（BMDL）。使用5%的基准反应（BMR），我们估计男性中U-Cd对不良肾脏效应标志物的BMDL分别为：eGFR为2.9、β2-MG为1.8、%TRβ2-MG<95%时为1.8以及%TRβ2-MG<90%时为3.6μg/g Cr；女性中分别为：CrCl为3.5、β2-MG为2.5、%TRβ2-MG<95%时为2.6以及%TRβ2-MG<90%时为3.9μg/g Cr。获得的肾小管效应的BMDL为1.8 - 3.6µg/g Cr，肾小球效应的BMDL为2.9 - 3.5µg/g Cr；与一般人群的暴露水平相比，这些数值不算很高。本研究中计算出的BMDL为保护普通居民或工人免受镉暴露的不良健康影响的措施提供了重要信息。
