A TIERED APPROACH FOR AGGREGATE EXPOSURE ASSESSMENT - THE CASE OF BISPHENOL-A

The study describes the tiered aggregate exposure assessment methodology supported by a computational platform) developed to provide a realistic estimation of exposure to substances from multiple sources, pathways and routes. A decision tree for moving from lower to higher Tiers of analysis is based on the Risk Characterization Ratio (RCR) derived in each Tier. If RCR is higher than one, a refinement of the assessment is required, using more refined data, models and assimilation of complex data (e.g biomarkers and use of toxicokinetic models) as well as Biomonitoring Equivalents for RCR assessment. The applicability of the overall methodology was tested in the BPA case study. Tier 1 assessment indicated that all consumer exposure scenarios (except premature neonates hosted in intensive care units) are below the EFSA tolerable daily intake (TDI) value. Identification of individual consumer exposure scenarios where RCR exceeds 1, triggered a two-stage Tier 2 analysis, incorporating the use of probability distributions for exposure determinants and a more detailed multimedia environmental model. Tier 2b analysis incorporated in addition a detailed toxicokinetic analysis of BPA, as well as the use of a Biomonitoring Equivalence (BE) value (derived as the internal dose corresponding to a constant oral dosing to an adult equal to the EFSA TDI) for reckoning RCR. Due to BPA specific toxicokinetic characteristics (very rapid 1st pass metabolism and strong binding to red blood cells and plasma proteins), significant bioavailability differences were identified depending on the developmental stage (glucuronidation, which is the major detoxification pathway, is considered to be immature in neonates and infants) and the administration route. Thus, specific exposure scenarios indicating an uptake lower than EFSA TDI (related to neonates and infants), correspond to an internal dose close (or even higher) than the BE value derived based on EFSA TDI.