Application of an integrated approach to evaluate health risks for toxic chemicals by linking multimedia environmental and PBPK models
Résumé
The paradigm of health risk assessment may consist of two main pillars, i.e., the exposure and dose-response assessments. Human exposure to chemicals via multiple pathways can be estimated by environmental multimedia models, which calculate the distribution of chemicals in the component media, i.e., air, water, soil, plants, and animal media. Combined with the information about human behaviors such as dietary habits, time spent outside, and etc, the multimedia models can provide an estimation of the daily chemical intake by inhalation or ingestion by humans. Physiologically based pharmacokinetic (PBPK) models are used to estimate the body burden of toxic chemicals throughout the entire human lifespan, integrating the evolution of the physiology and anatomy from childhood to advanced aged. The use of such PBPK models overcomes the limitations that dose-response modelling holds, e.g., it simply determines the relationship between the dose and the probability of an effect. The European project 2-FUN (Full-chain and UNcertainty Approaches for Assessing Health Risks in FUture ENvironmental Scenarios) aims at improving the approaches currently used in exposure and dose-response assessments. According to the aim of that project, an environmental multimedia model and a generic PBPK model are coupled as an integrated tool (2-FUN tool) and built up on a platform system, Ecolego. This study presents here the first application of the integrated tool to perform the full-chain risk assessment of a chemical for human health, considering multiple exposure pathways of chemical via inhalation of out-door air, and ingestion of water and foods. For this application of the tool, a case study was designed based on the information available in a region situated on the Seine river watershed, downstream of the Paris megacity and Benzo(a)pyrene (B(a)P) was selected as a target chemical substance. This study focuses especially on the propagation of uncertainty and inter-individual variability along the modelling chain. A probabilistic simulation was then performed to identify the input parameters and exposure pathways sensitive to model outputs (e.g., internal effective concentrations in organs).
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