Endocrine Abstracts

Cadmium (Cd) is a ubiquitously present toxic metal with an established ability to induce endocrine disruption, in literature often referred to as metalloestrogen. Some of the major uncertainties connected with endocrine disrupting chemicals (EDCs) in general, are low-dose exposure and the presence of nonmonotonic dose-response curves. This study aims to elucidate the presence of a dose-response relationship between the measured Cd levels in the tissue (internal dose) and estrogen levels in serum (hormonal response). The study was conducted at the Clinic for Oncology of the Clinical Hospital Center ’Bežanijska kosa’, Belgrade, Serbia in the period between January and September 2019 and included 55 patients diagnosed with breast cancer and 41 women with benign breast changes. All participants were further classified based on their menopausal status. Prior to surgery, venous blood samples were obtained from the anterior cubital vein after a 12 h fasting period and estradiol levels were determined in serum. After surgical tissue removal, Cd levels were determined in the tumor and the surrounding healthy breast tissue. Tissue samples were mineralized using wet digestion and Cd levels were determined using atomic absorption spectrometry. Dose-response modeling was performed using PROAST software version 67.0 (the Dutch National Institute for Public Health and the Environment, RIVM). Data on estradiol and Cd levels were analyzed as continuous individual data using menopausal status the presence of malignant/benign change as variable factors. Benchmark response was set to 10% and the averaging method was used to calculate the Benchmark dose (BMD) interval. Akaike information criterion was used to evaluate the model. The mathematical relationships between the concentration of Cd in the surrounding healthy/tumor tissue and the levels of estradiol in the serum of the subjects has been shown and BMD values were calculated. Rather low calculated BMD values indicate that even levels lower than 1 ng Cd/g breast tissue can lead to a 10% change in measured estrogen serum levels. These results implicate the presence of the dose-response behavior of EDCs and propose this method for investigating the possible presence of nonmonotonic dose-response curves, as well. Moreover, the obtained results testify that the BMD concept can be used as an approach to analyze human data. Further research on this topic is necessary so that the extrapolation of data from animals to humans can be, at least partly, replaced by the process applied in this study, thus facilitating risk assessment, especially for EDCs.