Physiologically-based pharmacokinetic and toxicokinetic models for estimating human exposure to five toxic elements through oral ingestion.

Biological monitoring and physiologically-based pharmacokinetic (PBPK) modelling are useful complementary tools in quantifying human exposure to elements in the environment. In this work, we used PBPK models to determine the optimal time for collecting biological samples in a longitudinal study to determine if participants who consumed allotment produce had been exposed to arsenic, cadmium, chromium, nickel or lead. There are a number of PBPK models for these elements published in the literature, which vary in size, complexity and application, given the differences in physiochemical properties of the elements, organs involved in metabolism and exposure pathways affected. We selected PBPK models from the literature to simulate the oral ingestion pathway from consumption of allotment produce. Some models required modification by reducing or removing selected compartments whilst still maintaining their original predictability. The performance of the modified models was evaluated by comparing the predicted urinary and blood elemental levels with experimental data and other model simulations published in the literature. Overall, the model predictions were consistent with literature data (r > 0.7, p < 0.05), and were influential in predicting when samples should be collected. Our results demonstrate the use of mathematical modelling in informing and optimising the design of longitudinal studies.