Integrated Exposure Modeling for Human Biomonitoring Data Assimilation

Abstract

The integrated exposure assessment framework in HBM4EU aims at introducing a comprehensive methodological approach which will be implemented in a computational platform. The aim is to assess the source-to-dose continuum of a large space of chemical substances, towards the effective assimilation of human biomonitoring (HBM) data. The platform will integrate environmental fate, exposure and internal dose dynamically in time and across different spatial resolutions (from local to global). This description requires the use of multimedia environmental and micro-environmental modelling, exposure analysis incorporating multiple pathways and routes of exposure, and Physiology Based ToxicoKinetic (PBTK) modelling. Exposure analysis up to internal dose, will allow the interpretation of actual dosimetry to target tissues to in vitro assay results. This is of particular importance for the precise estimation of doses that relate to molecular perturbations within adverse outcome pathways (AOPs). Biomonitoring data interpretation is another challenge of the methodology, described as the “reverse modeling” calculations for exposure reconstruction. Following this, and based on the amount and quality of prior information, quantitative predictions, ranging from the overall exposure burden up to pathway/route specific information could be made; this will provide a very comprehensive instrument for policy makers, that will allow them to point out the cost-efficient interventions (which sources contribute mostly to exposure), directly from HBM data. The applicability of the methodology has been demonstrated in the case of bisphenol-A, Exposure reconstruction of available HBM data resulted in very low intake estimates, while the use of in vitro data regarding its estrogenic activity, indicated that there is no reason for concern for individual or aggregate scenarios of BPA exposure in the EU population.