Risk Assessment of Perfluorooctane Sulfonate (PFOS) using Dynamic Age Dependent Physiologically based Pharmacokinetic...

The widespread use of Perfluorooctane sulfonate (PFOS) in everyday life, its long half-life, and the lipophilicity that makes it easily accumulate in the body, raises the question of its safe exposure among different population groups. There are currently enough epidemiological studies showing evidence of PFOS exposure and its associated adverse effects on humans. Moreover, it is already known that physiological changes along with age e.g. organ volume, renal blood flow, cardiac output and albumin concentrations affect chemicals body burden. Human biomonitoring cohort studies have reported PFOS concentrations in blood and autopsy tissue data with PFOS present in sensitive organs across all human lifespan. However, to interpret such biomonitoring data in the context of chemical risk assessment, it is necessary to have a mechanistic framework that explains show the physiological changes across age affects the concentration of chemical inside different tissues of the human body. PBPK model is widely and successfully used in the field of risk assessment. The objective of this manuscript is to develop a dynamic age-dependent PBPK model as an extension of the previously published adult PFOS model and utilize this model to predict and compare the PFOS tissue distribution and plasma concentration across different age groups. Different cohort study data were used for exposure dose reconstruction and evaluation of time-dependent concentration in sensitive organs. Predicted plasma concentration followed trends observed in biomonitoring data and model predictions showed the increased disposition of PFOS in the geriatric population. PFOS model is sensitive to parameters governing renal resorption and elimination across all ages, which is related to PFOS half-life in humans. This model provides an effective framework for improving the quantitative risk assessment of PFOS throughout the human lifetime, particularly in susceptible age groups. The dynamic age-dependent PBPK model provides a step forward for developing such kind of dynamic model for other perfluoroalkyl substances.