INTEGRA: From Global Scale Contamination To Tissue Dose

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Sarigiannis, Dimosthenis; Karakitsios, Spyros; Gotti, Alberto; Loizou, George; Cherrie, John; Smolders, Roel; De Brouwere, Kathleen; Galea, Karen; Jones, Kate; Handakas, Evangelos; Papadaki, Krystalia; Sleeuwenhoek, Anne Show More Hide
exposure; modelling platform; PBTK; Bisphenol
artifact description
The objective of the INTEGRA project is to bring together all information necessary for assessing the source-to-dose continuum over the entire life cycle of substances covering an extensive chemical space through the use of QSARs. The major outcome of INTEGRA is a comprehensive computational platform that integrates multimedia environmental and micro-environmental fate, exposure and internal dose within a dynamic framework in time. The platform allows multimedia interactions across different spatial scales, taking into account environmental releases and related processes at global, regional and local scale, up to the level of personal microenvironment. Coupling seamlessly exposure models with refined computational tools for internal dosimetry transforms risk assessment of environmental chemicals since it allows risk characterization to be based on internal dosimetry metrics. In this way high throughput system data such as the ones generated by Tox21 in vitro testing can be used. This opens the way towards a higher level of assessment that incorporates refined exposure (tissue dosimetry) and toxicity testing (Biological Pathway Altering Dose – BPAD) associated to environmental contamination at different scales. The applicability of INTEGRA was tested on bisphenol-A. Tier 1 assessment (environmental releases based on production volumes, worst case exposure estimates and a Tolerable Daily Intake of 50μg/kg_bw/d) indicated that specific exposure scenarios (i.e. bottle fed neonates and premature infants hosted in intensive care units) are close to the legislative thresholds. The refined assessment incorporating probabilistic analysis, actual environmental release data, detailed consumer exposure modelling and the use of BPAD as risk characterization metric, resulted in increased margins of safety compared to conventional risk assessment.