Extended Lifetime Physiologically Based Pharmacokinetic Modeling and Risk Assessment of Multi-Congener PCB Exposure in the Japanese Population

Building on a previously developed multi-congener PBPK framework, this study examines the lifetime accumulation of 18 polychlorinated biphenyl (PCB) congeners in Japanese males and females from 1 to 70 years of age. The lifetime extension combined childhood exposure estimates derived from Japanese National Health and Nutrition Survey seafood-consumption data, assuming an 11% tuna contribution, with stochastic adult exposure histories based on tuna-consumption frequencies from a Japanese dietary survey. Age-dependent physiology and congener-specific kinetics were incorporated to simulate PCB accumulation across life stages. Monte Carlo simulations of 2400 individuals per sex, sensitivity analysis, and risk characterization were conducted to examine population variability, influential parameters, and dietary exposure implications. At age 70, summed whole-blood PCB concentrations were 0.47 ± 0.53 ng/mL in males and 0.39 ± 0.45 ng/mL in females (mean ± standard deviation). Fat exhibited the highest concentrations: 77 ± 86 ng/mL in males and 64 ± 74 ng/mL in females; female mammary concentrations reached 51 ± 59 ng/mL. Population distributions were strongly right-skewed, primarily because of tuna-consumption frequency, while the fat partition coefficient was the dominant sensitivity parameter. Comparison with biomonitoring observations indicated that the model reproduced broad concentration patterns but underestimated several persistent PCB congeners. No simulated individual exceeded the selected dietary benchmarks or German human biomonitoring comparison values; however, the latter finding is conditional on model bias, particularly the underprediction of PCB-138, PCB-153, and PCB-180, which constitute the HBM-PCB indicator, and does not establish population-level non-exceedance. By extending the PBPK framework across childhood and adulthood, this study provides a basis for examining lifetime PCB internal dosimetry and identifying priorities for improving kinetic parameters and exposure characterization.