Co-PBK: a computational biomonitoring tool for assessing chronic internal exposure to chemicals and metabolites

Abstract

Toxic chemicals are released into the environment through diverse human activities. An increasing number of chronic diseases are associated with ambient pollution, thus posing a threat to people. Given the high consumption of resources for human biomonitoring, this study proposed coupled physiologically-based kinetic (co-PBK) modeling matrices as a biomonitoring tool for simplifying chronic internal exposure estimates of environmental chemicals and their metabolites using naphthalene (NAP) and its metabolites (i.e., 1-OHN and 2-OHN) as simulation examples. According to the simulation of the steady-state mass among various organs/tissues via the co-PBK modeling matrices, fat had the highest potential bioaccumulation of NAP and its metabolites. With respect to body fluids, 1-OHN and 2-OHN tended to bioaccumulate more in the bile than in the urine. According to the sensitivity analysis, the calculated sensitivity factors for the first-order kinetics-based rate constants imply that due to the biotransformation process, target organs/tissues (e.g., liver and kidneys) would be continuously exposed to more NAP metabolites under chronic exposure. Meanwhile, 1-OHN may be more stably transported to the urine than 2-OHN for further human biomonitoring during long-term internal exposure. According to the case study of simulating population chronic exposure to NAP in Shenzhen, the co-PBK modeling estimated the population exposure to NAP with an intake rate of 8.77 × 10⁻² mg d⁻¹ and the aggregated urinary concentration of NAP metabolites of 2.60 μg L⁻¹. Furthermore, the accuracy of the urinary levels between the real-world data and the values simulated by the co-PBK modeling was assessed and the root-mean-square error of c_1-OHN,urine was found to be lower than that of c_2-OHN,urine.