Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Department of Clinical Science, Intervention and Technology, Karolinska Institute, 17177 Stockholm, Sweden.
Int J Environ Res Public Health. 2021 May 13;18(10):5177. doi: 10.3390/ijerph18105177.
The aim of this study was to determine the no observed adverse effect level (NOAEL), the lowest observed adverse effect level (LOAEL) and the benchmark dose low (BMDL) of cadmium exposure by re-evaluation of the dose-response relationship between cumulative cadmium exposure and renal tubular damage reported previously.
The participants were workers (326 men and 114 women) employed for at least three months between 1931 and 1982. Blood cadmium (Cd-B) and air cadmium (Cd-A) were collected at regular intervals with urinary β2-microglobulin as the tubular effect marker. Cumulative Cd-A and Cd-B were estimated by multiplying concentration and working period. The BMDL was calculated using Benchmark Dose Software (version 3.1.2). The benchmark response (BMR) was set at 5% or 10%.
By logistic regression, the NOAEL of mean cumulative Cd-B was 7122 months nmol/L. The LOAEL of cumulative Cd-A and least-squares cumulative Cd-B was 691 yrs μg/m and 8586 months nmol/L, respectively. Among various models for dose-response relationships, a probit model was adopted as the best fitting model. The obtained BMDLs of cumulative Cd-A were 272.3 yrs µg/m (BMR5%) and 707.5 yrs µg/m (BMR10%). The BMDLs of mean cumulative Cd-B were 3967.2 months nmol/L (BMR5%) and 7798.1 months nmol/L (BMR10%). The BMDLs of least-squares cumulative Cd-B were 3588.6 months nmol/L (BMR5%) and 8616.3 months nmol/L (BMR10%). Assuming a working period of 40 years, the BMDLs for BMR10% corresponded to 17.7 µg/m (Cd-A) and 1.8~2.0 µg/L (Cd-B).
This study provides new valuable information to enhance the reliability of limit values and thereby make a significant contribution to preventing the health effects of Cd in exposed workers.
本研究旨在通过重新评估先前报道的累积镉暴露与肾小管损伤之间的剂量-反应关系，确定镉暴露的无观察到不良效应水平（NOAEL）、最低观察到不良效应水平（LOAEL）和基准剂量低（BMDL）。
研究对象为 1931 年至 1982 年间至少工作三个月的工人（326 名男性和 114 名女性）。定期采集血镉（Cd-B）和空气镉（Cd-A），以尿β2-微球蛋白作为肾小管效应标志物。累积 Cd-A 和 Cd-B 通过浓度与工作时间的乘积来估算。使用 Benchmark Dose Software（版本 3.1.2）计算 BMDL。基准反应（BMR）设定为 5%或 10%。
通过逻辑回归，平均累积 Cd-B 的 NOAEL 为 7122 个月 nmol/L。累积 Cd-A 和最小二乘法累积 Cd-B 的 LOAEL 分别为 691 年μg/m 和 8586 个月 nmol/L。在各种剂量-反应关系模型中，采用概率单位模型作为最佳拟合模型。累积 Cd-A 的 BMDLs 分别为 272.3 年μg/m（BMR5%）和 707.5 年μg/m（BMR10%）。平均累积 Cd-B 的 BMDLs 分别为 3967.2 个月 nmol/L（BMR5%）和 7798.1 个月 nmol/L（BMR10%）。最小二乘法累积 Cd-B 的 BMDLs 分别为 3588.6 个月 nmol/L（BMR5%）和 8616.3 个月 nmol/L（BMR10%）。假设工作年限为 40 年，BMR10%对应的 BMDLs 分别为 17.7μg/m（Cd-A）和 1.8~2.0μg/L（Cd-B）。
本研究提供了新的有价值信息，有助于提高限值的可靠性，从而为预防暴露于镉的工人的健康影响做出重要贡献。
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