Integration of environmental and human PBPK exposure models: application of MERLIN-Expo modelling tool to POPs exposure in Venice lagoon

Abstract

MERLIN-Expo is a new tool for integrated exposure assessment recently developed under the FP7 project “4FUN”. MERLIN-Expo is a simulation platform providing a library of multimedia and physiologically-based pharmacokinetic (PBPK) models which can be coupled in order to estimate ecological and human exposures in complex scenarios. Models can be used to simulate fate of organic (PAHs, PCBs) and inorganic contaminants. Software enables end-user to apply set of functionalities such as uncertainty and sensitivity analysis, dynamic deterministic and probabilistic simulations in order to address different exposure and chemical fate problems. MERLIN-Expo was applied to assess the ecological and human exposure to PCBs and PCDDs in the Venice lagoon. The Phytoplankton, Aquatic Invertebrate and Fish models were developed and implemented in MERLIN-Expo library, subsequently integrated to create specific aquatic food web to dynamically simulate bioaccumulation in different aquatic species. Concentrations of PCBs and PCDDs in water were used as time-dependent inputs to run long term simulations. The estimated concentrations in edible aquatic species were then used to estimate daily human intake through the consumption of local seafood. The application of the PBPK model allowed to explore the time dependent accumulation of target chemicals in human tissues for several decades. Modelling results are tested against available monitoring data on chemical concentrations in edible aquatic species and concentrations in serum of adult men in Venice area to assess the reliability and applicability of the proposed tool to real complex scenarios. Full chain exposure assessment is then complemented by uncertainty and sensitivity analysis including local sensitivity methods, screening methods (e.g. Morris method), global regression methods (e.g. Standardised Regression Coefficients), and global variance based methods (e.g. FAST, EFAST, Sobol). These methods allow to follow for instance WHO (2008) recommendations to perform three stage uncertainty/sensitivity analysis, adopting qualitative, semi-qualitative, and quantitative methods. Integration of environmental and human exposure models in MERLIN-Expo allows comprehensive assessment of exposure and thus better characterisation of overall risk to human and environment especially in the case of higher tier assessment. This makes the tool interesting and promising for potential applications in different regulatory domains