Linking multimedia environmental and PBPK models to assess health risks of lead associated to drinking water - A case study

Abstract : Human exposure to chemicals through multiple pathways is classically estimated by the so-called 'multimedia models', calculating the distribution of contaminants among products of interest for humans (like drinking water, inhaled air, vegetables, meat, milk, etc). Combined to data describing human behavior (diet composition, time spent outside, etc), such multimedia models provide an estimation of the daily quantity inhaled or ingested by the population of interest. Once the exposure scenario is identified, the dose-response assessment is typically achieved by comparing exposure outputs (e.g, the daily intake) to reference doses, estimated from toxicological data. Coupling multi-media models for different exposure pathways with a generic physiologically based pharmacokinetic (PBPK) model for the human population enables to assess directly the impact of the exposure scenarios on the chemical's concentration in the target tissues.One aim of the European 2-FUN project (Full-chain and UNcertainty Approaches for Assessing Health Risks in FUture ENvironmental Scenarios) was to develop an integrated 'multimedia-PBPK' toolbox that also incorporates uncertainty and inter-individual variability analyses by Monte Carlo simulations, and different kinds of sensitivity analysis. In the present study, an integrated modeling approach was demonstrated for predicting internal tissue concentrations of chemicals by coupling a multimedia environmental model and a PBPK model. A case study was designed for a region situated on the Seine river watershed, downstream of the Paris megacity and for lead emitted from industrial zones in the region. The limited monitoring datasets of lead concentrations in bottom sediment and in raw river water, obtained at the downstream of Paris, were used to re-construct long-term daily concentrations of lead in river water. The re-construction of longterm series of lead level played a key role for the intermediate model calibration (conducted in multimedia model), and thus for improving model input to PBPK model. In order to take into account the parametric uncertainty in the model inputs, some input parameters relevant for the multimedia model were given by probability density functions (PDFs); some generic PDFs were updated with site-specific measurements by a Bayesian approach.This case study demonstrated the feasibility of a full-chain assessment combining multimedia environmental predictions and PBPK modeling, including uncertainty analysis.
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Submitted on : Wednesday, April 2, 2014 - 3:52:45 PM
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  • HAL Id : ineris-00970792, version 1
  • INERIS : EN-2011-118

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S. Maurau, Philippe Ciffroy, Céline Brochot, Y. Roustan, L. Marang. Linking multimedia environmental and PBPK models to assess health risks of lead associated to drinking water - A case study. 21. SETAC Europe annual meeting "Ecosystem protection in a sustainable world : a challenge for science and regulation", May 2011, Milan, Italy. ⟨ineris-00970792⟩

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