A multi-congener physiologically based pharmacokinetic approach for human polychlorinated biphenyl exposure through tuna consumption in Japan

• Population-based PBPK model developed for dietary PCBs exposure in Japan. • Multi-congener toxicokinetics integrated with stochastic tuna consumption. • Monte Carlo simulations capture interindividual variability in PCBs burdens. • Predicted blood PCBs levels align with reported biomonitoring data. • Framework improves interpretation of dietary exposure to persistent pollutants. Polychlorinated biphenyls (PCBs) remain persistent environmental contaminants of concern due to their bioaccumulative properties and ongoing dietary exposure through seafood consumption. In this study, a population-based physiologically based pharmacokinetic (PBPK) modeling framework was developed to quantify human exposure to mixed PCBs congeners through tuna consumption in Japan. The model integrates probabilistic tuna consumption frequency, variable portion sizes, and stochastic tuna species composition, and uses repeated Monte Carlo realizations to generate individual-specific dietary exposure scenarios representing inter-individual variability within the population. Congener-specific physicochemical properties were incorporated by simulating 18 PCB congeners individually using structure-based tissue–blood partition coefficients, and total PCB concentrations were obtained by summing congener-specific predictions. Lifetime exposure initialization was implemented to avoid zero-background assumptions. Eighteen PCB congeners accounting for approximately 98% of the dietary PCB burden were included. Population simulations for adult females and males over a ten-year exposure period produced moderately right-skewed distributions of whole-blood PCB concentrations. The predicted mean whole-blood PCB concentrations were 0.97 ng/mL for females and 1.08 ng/mL for males, with inter-individual variability primarily driven by stochastic dietary intake patterns, body weight (BW) differences, and congener-specific toxicokinetics. Modeled concentrations were comparable to reported biomonitoring data from Japan and other industrialized regions. Overall, this population-based, multi-congener PBPK framework provides an improved tool for interpreting biomonitoring data and characterizing dietary exposure to persistent organic pollutants.