Department of Toxicology "Akademik Danilo Soldatović", University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Albert Einstein College of Medicine, NY 10461, USA.
Environ Int. 2022 Jul;165:107313. doi: 10.1016/j.envint.2022.107313. Epub 2022 May 21.
The main objective of this research was to conduct a dose-response modeling between the internal dose of measured blood Cd, As, Hg, Ni, and Cr and hormonal response of serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). The study included 207 male participants from subjects of 5 different cohorts (patients with prostate, testicular, and pancreatic cancer, patients suffering from various thyroid and metabolic disorders, as well as healthy volunteers), enrolled from January 2019 to May 2021 at the Clinical Centre of Serbia in Belgrade, Serbia. Benchmark dose-response modeling analysis was performed with the PROAST software version 70.1, showing the hormone levels as quantal data. The averaging technique was applied to compute the Benchmark dose (BMD) interval (BMDI), with benchmark response set at 10%. Dose-response relationships between metal/metalloid blood concentration and serum hormone levels were confirmed for all the investigated metals/metalloid and hormones. The narrowest BMDI was found for Cd-testosterone and Hg-LH pairs, indicative of high confidence in these estimates. Although further research is needed, the observed findings demonstrate that the BMD approach may prove to be significant in the dose-response modeling of human data.
本研究的主要目的是在测量的血液中 Cd、As、Hg、Ni 和 Cr 的内剂量与血清睾酮、黄体生成素 (LH) 和卵泡刺激素 (FSH) 的激素反应之间进行剂量-反应建模。该研究包括来自塞尔维亚贝尔格莱德塞尔维亚临床中心的 5 个不同队列的 207 名男性参与者(前列腺癌、睾丸癌和胰腺癌患者、患有各种甲状腺和代谢紊乱的患者以及健康志愿者),他们于 2019 年 1 月至 2021 年 5 月入组。使用 PROAST 软件版本 70.1 进行基准剂量反应建模分析,将激素水平显示为定量数据。应用平均技术计算基准剂量 (BMD) 区间 (BMDI),以 10%作为基准反应。对于所有研究的金属/类金属和激素,均确认了金属/类金属血液浓度与血清激素水平之间的剂量-反应关系。对于 Cd-睾丸酮和 Hg-LH 对,BMDI 最窄,表明这些估计值的置信度很高。尽管需要进一步研究,但观察到的发现表明,BMD 方法在人体数据的剂量-反应建模中可能具有重要意义。