Lead exposure estimation through a physiologically based toxicokinetic model using human biomonitoring data and comparison with scenario-based exposure assessment: A case study in Korean adults.

Pb toxicity is linked to cardiovascular and nephrotoxicity issues. Exposure to this heavy metal can occur through food and drinking water. Therefore, this study aimed to evaluate Pb exposure and assess health risks in Korean adults using a physiologically based toxicokinetic (PBTK) model. Human blood Pb concentrations were monitored using the Korean National Environmental Health Survey (KoNEHS) Cycle 4. The average Pb exposure in Korean adults was 0.520 µg/kg bw/day. The PBTK results were compared with scenario-based results from the 2021 risk assessment report of five heavy metals, including Pb, conducted by the MFDS. Exposure determined through reverse dosimetry was approximately two times higher than scenario-based exposure (0.264 µg/kg bw/day). The higher exposure levels obtained during PBTK analysis may be attributed to sustained exposure within historically more contaminated living environments and the long half-life of Pb. These findings suggest that the PBTK-based method can quantify aggregated exposure levels in the body over time, potentially serving as a complementary tool to address the constraints of scenario-based assessment methods for integrated risk assessment. Moreover, this model is convenient and cost-effective compared with scenario-based exposure estimation. These findings can facilitate the application of model for tracking continuous national changes in hazardous substance levels.

Novel Estrogen Receptor Dimerization BRET-Based Biosensors for Screening Estrogenic Endocrine-Disrupting Chemicals.

The increasing prevalence of endocrine-disrupting chemicals (EDCs) in our environment is a growing concern, with numerous studies highlighting their adverse effects on the human endocrine system. Among the EDCs, estrogenic endocrine-disrupting chemicals (eEDCs) are exogenous compounds that perturb estrogenic hormone function by interfering with estrogen receptor (ER) homo (α/α, ß/ß) or hetero (α/ß) dimerization. To date, a comprehensive screening approach for eEDCs affecting all ER dimer forms in live cells is lacking. Here, we developed ER dimerization-detecting biosensors (ERDDBs), based on bioluminescence resonance energy transfer, for dimerization detection and rapid eEDC identification. To enhance the performance of these biosensors, we determined optimal donor and acceptor locations using computational analysis. Additionally, employing HaloTag as the acceptor and incorporating the P2A peptide as a linker yielded the highest sensitivity among the prototypes. We also established stable cell lines to screen potential ER dimerization inducers among estrogen analogs (EAs). The EAs were categorized through cross-comparison of ER dimer responses, utilizing EC values derived from a standard curve established with 17ß-estradiol. We successfully classified 26 of 72 EAs, identifying which ER dimerization types they induce. Overall, our study underscores the effectiveness of the optimized ERDDB for detecting ER dimerization and its applicability in screening and identifying eEDCs.