PROBABILISTIC AND FULL-CHAIN RISK ASSESSMENT OF THE CHEMICAL ACCUMULATION ON HUMAN BODY USING AN INTEGRATED MODELLING TOOL

Mathematical models have been developed to address diverse issues. Especially environmental multimedia models are now well recognized as useful tools for environmental and health risk assessment and management. This dissertation consists of three main pillars: (i) the introduction of the newly developed integrated modelling tool (2-FUN tool) that deals with environmental and health risk assessment, (ii) the investigation of statistical approaches to derive density functions (PDFs) of input parameters of interest, and (iii) the application of the 2-FUN tool for a designed case study. Chapter 1 presents general roles of mathematical models for health and environmental risk assessment of chemicals, the importance to consider parametric uncertainty, and the extensive review on existing modelling methodologies. At the end of the model review, main features of the 2-FUN tool are pointed out as follows: (i) Its capability to conduct a full-chain risk assessment on a common system, which allows linking the simulation of chemical fate in the environmental media, multiple pathways of exposure, and the detailed analysis for multiple effects in different target tissues in human body, (ii) it contains a wide range of methods for sensitivity and uncertainty analyses, and (iii) it can be user-friendly because of its effective graphical simulation interface and its flexibility, which facilitates users to design scenarios for target regions and arrange the tool on their own ways. The conceptual and theoretical aspects of the 2-FUN tool are summarized in Chapter 2. The focus of Chapter 3 is set at the detailed presentation of two advanced statistical approaches to derive probabilistic density function (PDF) for the two parameters used in the freshwater compartment of the 2-FUN tool: the settling velocity of particles that is a driving factor influencing the transfer of particles at the water-sediment interface in fresh-water system, and the fish bioconcentration factor (BCF) for metal that represents the accumulation of a given chemical in organisms arising by water uptake. Finally, Chapter 4 depicts how the 2-FUN tool can be applied based on a designed case study and shows the feasibility of the integrated modelling approach to couple an environmental multimedia and a PBPK models, considering multi-exposure pathways, and thus the potential applicability of the 2-FUN tool for health risk assessment.