Development and application of generic toxicokinetic models in fish to environmental risk assessment of chemicals
Résumé
One of the goals of environmental risk assessment is to protect animal populations and the whole ecosystem from adverse effects resulting from exposure to single or multiple chemicals. In principle, risk assessment methodologies rely on combining estimates of exposure to the chemical(s) with toxicity data (hazard) used for risk characterisation. Exposure assessment aims to quantify “external dose”, as the amount of chemical agent(s) that reaches an organism. Hazard assessment for a chemical aims to quantify the relationship between dose and toxicity so that reference points can be set to derive environmental standards for specific protection goals. Over the last two decades, many research efforts have aimed to improve the quantification of such dose response relationships through the integration of “external dose” and “internal dose” namely toxicokinetic (TK)/ADME (Absorption, Distribution, Metabolism, and Excretion) processes. For this purpose, TK models have been developed to estimate internal doses from external doses in a time dependent manner, characterise the consequence of metabolism to identify the toxic species for a given compound (parent compound/metabolite) as well as extrapolate between laboratory and environmental conditions or between species. The purpose of this project is to develop a generic TK model for fish species to predict internal doses under different environmental scenarios of exposure. The model will be adaptable to a number of teleost fish species and validated by using data for studies on regulated products (e.g. pesticides) and environmental contaminants. Extensive literature searches will be performed to review models and tools incorporating TK for environmental risk assessment, collect biological and physiological parameters for given fish species and TK parameters for chemicals of environmental relevance. From this data collection exercise, tools aiming at predicting TK parameters for a number of fish species (i.e. interspecies extrapolation) will be developed. These tools will allow the calibration of fish physiologically-based TK (PB-TK) model taking into account several compartments (e.g. liver, fat) to model ADME processes for chemicals under different exposure scenarios. Finally, the predictive ability of the model and the uncertainties will be assessed for both TK parameters taking into account fish species differences and prediction of toxicity parameters.