정승현 (국립순천대학교 약학대학) | 한빛사논문 > 한빛사Human biomonitoring provides direct measures of internal exposure to environmental chemicals, but translating biomarker concentrations into quantitative external exposure and risk estimates remains challenging. Chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) are widely used biocides, and population exposure is typically assessed via urinary biomarkers. However, a quantitative framework connecting biomonitoring data to external dose and health risk is currently lacking. This study aims to quantitatively reconstruct external CMIT/MIT exposures from human urinary biomonitoring data using a population pharmacokinetic (PopPK) model and to assess human health risk via integrating reverse dosimetry with an internal dose-based reference dose (RfD). A human-scale PopPK model capable of quantitatively describing urinary excretion of N-methylmalonamic acid and the mercapturic acid metabolite M-12 following oral CMIT/MIT exposure was developed. Model parameters were estimated using nonlinear mixed-effects modeling and evaluated via bootstrap analysis, visual predictive checks, goodness-of-fit diagnostics, and normalized prediction distribution error analysis. The validated model was then applied to adult biomonitoring data from the German Environmental Sample Bank and to pediatric and adolescent survey data. External exposure doses were reconstructed via reverse dosimetry, accounting for inter-individual PK variability. Human health risk was quantified using the margin of exposure (MOE) approach, referencing an internal dose-derived oral RfD of 0.02 mg/kg/day. The final PopPK model reliably captured urinary biomarker excretion dynamics at population and individual levels. Parameter estimates were robust, with bootstrap medians closely aligned with the final model values. Reconstructed external exposures exhibited no consistent long-term increasing or decreasing trend in adults and no systematic age- or sex-related pattern in pediatric and adolescents. Most exposure scenarios yielded MOE values > 10, while only extreme upper-bound conditions yielded MOEs of approximately 2-5. Even under conservative assumptions, all MOE values remained above 1. This study demonstrates that human biomonitoring data can be quantitatively translated into external exposure and risk metrics using a PopPK-based reverse dosimetry framework. The findings indicate that current CMIT/MIT exposure levels in the general population are unlikely to pose health concerns under typical environmental conditions. The integrated biomonitoring-modeling approach offers a regulatory-relevant framework for linking internal biomarkers to external exposure and health risk assessment.
정승현 (국립순천대학교 약학대학) | 한빛사논문 > 한빛사Quantitative extrapolation of inhalation toxicity data from experimental animals to humans remains challenging because identical external aerosol exposures do not necessarily produce equivalent internal respiratory doses across species. This study aimed to establish a quantitative computational framework for animal-to-human extrapolation by integrating species-specific respiratory dosimetry using the Multiple-Path Particle Dosimetry (MPPD) model. Species-specific respiratory dosimetry models were developed for mice, rats, and adult humans using MPPD v3.04 under identical aerosol exposure conditions. Regional respiratory deposition was compared across species, while the effects of aerosol particle size (mass median aerodynamic diameter, MMAD) and human breathing scenarios were systematically evaluated. Regional deposition outputs were further integrated to derive quantitative dosimetry indices, human equivalent concentrations (HECs), and species correction factors (SCFs) for animal-to-human extrapolation. Marked interspecies differences were observed in regional respiratory deposition despite identical aerosol exposure conditions. Rodents exhibited predominant deposition within the extrathoracic region, whereas humans demonstrated substantially greater pulmonary deposition. Species-specific deposition differences became more pronounced with increasing MMAD, and pulmonary delivery in humans was strongly influenced by breathing scenario. Quantitative dosimetry analysis demonstrated that pulmonary deposition in humans was approximately three-fold greater than in rodents under the reference exposure condition, resulting in substantially different regional respiratory deposition metric despite equivalent external exposures. The proposed HEC and SCF metrics enabled quantitative comparison and translation of animal and human exposure conditions using MPPD-derived regional deposition metrics rather than external aerosol concentration alone. This study presents a species-specific respiratory dosimetry framework for quantitative animal-to-human extrapolation of inhaled aerosols. By integrating regional respiratory deposition with HEC and SCF analyses, the proposed framework provides a mechanistically informed strategy for inhalation dosimetry, human equivalent exposure estimation, and future integration with physiologically based pharmacokinetic modeling and inhalation risk assessment.
정승현 (국립순천대학교 약학대학) | 한빛사논문 > 한빛사Cerium oxide (CeO2) nanoparticles are widely used in industrial and commercial applications, resulting in increasing concerns regarding potential inhalation-related health risks. However, quantitative translation of inhalation exposure into human risk metrics remains limited due to the lack of integrated mechanistic frameworks linking respiratory deposition, toxicokinetics, toxicodynamics (TD), and risk assessment. The present study developed an integrated multiple-path-particle-dosimetry (MPPD)–physiologically-based-toxicokinetic (PBTK)–TD modeling framework for CeO2 nanoparticles inhalation and applied it to model-based human risk characterization. A rat MPPD–PBTK model was first established using published inhalation biodistribution data and successfully reproduced CeO2 concentrations in lung, serum, liver, kidney, spleen, gastrointestinal tract, urine, and feces (97.26% and 98.63% of observations within 2-fold and 3-fold-error, respectively). The model was subsequently extrapolated to humans by incorporating human-specific respiratory and physiological parameters. A reduced-order TD model describing reactive-oxygen-species generation, glutathione depletion, caspase-3 activation, and cell viability reduction was developed using published BEAS-2B toxicity data (100% of observations within 2-fold-error). Sensitivity analyses identified exposure concentration, pulmonary deposition fraction, pulmonary effective-exposure kinetics, and viability-related parameters as major determinants of model outputs. Monte-Carlo uncertainty propagation revealed substantial dispersion in pulmonary effective concentration and viability responses arising from combined plausible physiological variability and parameter/model uncertainty. Within the BEAS-2B-based TD framework, viability-based criteria yielded lower model-derived exposure thresholds than the selected ROS- or caspase-3-based criteria. Among the evaluated exploratory cellular-response criteria, the lowest model-derived risk-based human-equivalent concentration was obtained for viability <95% at 180 h, yielding 0.0138 mg/m3 for the 24-h exposure scenario at a 10% model-based threshold-exceedance level when calculated using direct concentration-dependent reverse dosimetry.2026 Honam Regional Future Drug Development Convergence Education & Research Division The 1st Academic Exchange Symposium in Gwangju (Speaker)
2026 KALAS (Korean Association for Laboratory Animal Sciences) International Symposium in Jeju
2026 Spring Conference of the Korean Society of Environmental Toxicology and Health in Seoul
2026 AAPS National Biotechnology Conference in SAN DIEGO, CA, USA
2026 Spring International Convention of The Pharmaceutical Society of Korea (PSK) in Osong
2026 16th International Conference on Bioscience, Biochemistry and Bioinformatics
2025 Honam Branch Conference of The Pharmaceutical Society of Korea in Gwangju
2025 International Conference of the Korean Society of Pharmaceutical Sciences and Technology in Seoul
2025 Fall International Convention of The Pharmaceutical Society of Korea (PSK) in Seoul
ISSX 2025 14th International Meeting in Chicago, Illinois, USA
2025 Spring International Convention of The Pharmaceutical Society of Korea (PSK) in Daegu
2025 Seminar: Integrating multidisciplinary technologies for a progressive leap forward in pharmacology-toxicology in Gwangju (Speaker)
2024 Honam Branch Conference of The Pharmaceutical Society of Korea in Iksan
2024 International Conference of the Korean Society of Pharmaceutical Sciences and Technology in Seoul
2024 Fall International Convention of The Pharmaceutical Society of Korea (PSK) in Seoul
2024 Spring Conference of Korean Society of Environmental Health and Toxicology in Seoul
2024 Spring International Convention of The Pharmaceutical Society of Korea (PSK) in Busan
2023 Honam Branch Conference of The Pharmaceutical Society of Korea in Jeju
2023 International Conference of the Korean Society of Pharmaceutical Sciences and Technology in Seoul
2023 The 39th Annual Meeting of KSOT/KEMS in Jeju
2023 Fall International Convention of The Pharmaceutical Society of Korea (PSK) in Suncheon-si
2023 Asia-Oceania Mass Spectrometry Conference & Annual Meeting of The Korean Society Mass spectrometry in Jeju
2023 Spring International Convention of The Pharmaceutical Society of Korea (PSK) in Gyeongju
2023 Research grant award ceremony from Handok Pharmaceuticals
2023 Workshop: Understanding and Sharing Risk Assessment Technology (Human Exposure Assessment Using the PBPK Model) in Seoul (Speaker)
2023 Seminar: Drug Administration Route and Delivery Efficiency in Gwangju (Speaker)
2022 Honam Branch Conference of The Pharmaceutical Society of Korea in Gwangju (Speaker & Poster presentation)
2022 Fall International Convention of The Pharmaceutical Society of Korea (PSK) in Jeju