A09_Exposure reconstruction methods and HBM data assimilation

Presentation for HBM4EU Training School in Nijmegen (19-23 November 2018). The aim of this course is to help the trainees to understand the logical workflow and the mathematical framework for assimilating biomonitoring data through exposure reconstruction. In the reverse dosimetry approach, exposure components are quantified and are related to the observed biomarkers concentrations. Human biomonitoring typically is an integrative measure of different exposure episodes along various routes and over different time scales; thus, it is often very difficult to reconstruct the primary exposure routes from HBM data alone. However, several mathematical approaches have been developed to reconstruct exposures related to population biomonitoring studies, and can be subdivided in a number of different approaches summarized below: – Deterministic methods o Intake mass balance: This is the simplest method for approximating the daily intake dose. o Deterministic method using a PBTK model. This is a deterministic method that associates measured biomarkers with actual intake, using single values. This can beapplied either with comprehensive PBTK model, or with a simple PK model. – Stochastic methods o Exposure conversion factor: This is a stochastic method that incorporates variability and uncertainty in both exposure scenario and PBTK model parameterization, o Bayesian approach: This is the most comprehensive approach, able to address complex exposure scenarios, dynamic in time and provides reliable results for both rapidly and non-rapidly metabolized compounds, addressing all kinds of uncertainties and variabilities introduced in the modeling process. All the above methods are described in this course and examples of exposure reconstruction are given.