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Updated: Aug 20, 2026

Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
Published on: June 17, 2015
Mixed-Effects Physiologically Based Pharmacokinetic Modeling of Methylmercury across the Maternal-Infant Continuum:
1College of Nursing Science, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul02447, Republic of Korea.
Abstract:
Prenatal methylmercury (MeHg) exposure drives neurodevelopmental impairment in East Asia, but existing physiologically based pharmacokinetic (PBPK) models rely on population-average parameters and single-matrix validation. We developed a three-submodel mixed-effects PBPK (MEM-PBPK) framework validated against maternal blood, cord blood, urinary, and breast milk mercury in two Korean birth cohorts (Ko-CHENS, n = 3,625; NOEMOC, n = 242). Clinical chemistry-individualized Michaelis-Menten placental kinetics reproduced second-trimester blood mercury (mean fold error, MFE = 0.946); empirical Bayes random effects improved cord blood prediction to MFE = 0.954 (within-2-fold = 100%). Biomarker bridging replicated +38.7% raw and -32.6% creatinine-corrected urinary trimester changes (p < 0.001), and breast milk MFE = 1.057. Critically, postnatal glomerular filtration maturation prolonged neonatal inorganic mercury renal half-life ∼5-fold (∼160 d at birth vs ∼32 d in adults; partial rank correlation coefficient, PRCC > 0.99) without affecting blood MeHg, demonstrating that blood-only biomonitoring systematically underestimates neonatal kidney mercury burden. These findings support cord-blood-anchored multimatrix biomonitoring and postnatal urinary iHg surveillance in East Asian populations.
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