Department of Toxicology "Akademik Danilo Soldatović", University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221, Belgrade, Serbia.
Department of Toxicology "Akademik Danilo Soldatović", University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221, Belgrade, Serbia.
Environ Res. 2022 Dec;215(Pt 2):114283. doi: 10.1016/j.envres.2022.114283. Epub 2022 Sep 9.
The major goal of this study was to estimate the correlations and dose-response pattern between the measured blood toxic metals (cadmium (Cd), mercury (Hg), chromium (Cr), nickel (Ni))/metalloid (arsenic (As)) and serum insulin level by conducting Benchmark dose (BMD) analysis of human data. The study involved 435 non-occupationally exposed individuals (217 men and 218 women). The samples were collected at health care institutions in Belgrade, Serbia, from January 2019 to May 2021. Blood sample preparation was conducted by microwave digestion. Cd was measured by graphite furnace atomic absorption spectrophotometry (GF-AAS), while inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure Hg, Ni, Cr and As. BMD analysis of insulin levels represented as quantal data was done using the PROAST software version 70.1 (model averaging methodology, BMD response: 10%). In the male population, there was no correlation between toxic metal/metalloid concentrations and insulin level. However, in the female population/whole population, a high positive correlation for As and Hg, and a strong negative correlation for Ni and measured serum insulin level was established. BMD modelling revealed quantitative associations between blood toxic metal/metalloid concentrations and serum insulin levels. All the estimated BMD intervals were wide except the one for As, reflecting a high degree of confidence in the estimations and possible role of As as a metabolic disruptor. These results indicate that, in the case of As blood concentrations, even values higher than BMD (BMDL): 3.27 (1.26) (male population), 2.79 (0.771) (female population), or 1.18 (2.96) μg/L (whole population) might contribute to a 10% higher risk of insulin level alterations, meaning 10% higher risk of blood insulin increasing from within reference range to above reference range. The obtained results contribute to the current body of knowledge on the use of BMD modelling for analysing human data.
本研究的主要目的是通过对人体数据进行基准剂量（BMD）分析，估计测量的血液有毒金属（镉（Cd）、汞（Hg）、铬（Cr）、镍（Ni））/类金属（砷（As））与血清胰岛素水平之间的相关性和剂量-反应模式。该研究涉及 435 名非职业暴露个体（217 名男性和 218 名女性）。样本于 2019 年 1 月至 2021 年 5 月在塞尔维亚贝尔格莱德的医疗机构采集。通过微波消解进行血样准备。采用石墨炉原子吸收分光光度法（GF-AAS）测定 Cd，电感耦合等离子体质谱法（ICP-MS）测定 Hg、Ni、Cr 和 As。采用 PROAST 软件版本 70.1（模型平均方法，BMD 反应：10%）对作为定量数据的胰岛素水平进行 BMD 分析。在男性人群中，有毒金属/类金属浓度与胰岛素水平之间没有相关性。然而，在女性人群/整个人群中，发现 As 和 Hg 之间存在高度正相关，Ni 和测定的血清胰岛素水平之间存在强烈负相关。BMD 建模揭示了血液有毒金属/类金属浓度与血清胰岛素水平之间的定量关联。除了 As 的 BMD 间隔（BMDL）外，所有估计的 BMD 间隔都很宽：3.27（1.26）（男性人群）、2.79（0.771）（女性人群）或 1.18（2.96）μg/L（整个人群），这反映了对估计值的高度置信度和 As 作为代谢干扰物的可能作用。这些结果表明，在 As 血液浓度的情况下，即使是高于 BMD（BMDL）的值：3.27（1.26）（男性人群）、2.79（0.771）（女性人群）或 1.18（2.96）μg/L（整个人群），也可能导致胰岛素水平改变的风险增加 10%，即血液胰岛素从参考范围内增加到参考范围以上的风险增加 10%。所获得的结果有助于当前关于使用 BMD 建模分析人体数据的知识体系。
