The overall goal of this dissertation is to contribute to the development of best available practice in environmental multimedia fate and multipathway exposure modelling for human health and ecosystem impacts, addressing several important aspects. Environmental multimedia models relate environmental emissions to impacts (or risk factors) combining multimedia fate and multipathway exposure estimates with effect assessment data. Many organic chemicals formed in combustion and released to air as well as organic chemicals released to air, water, and soil from industrial activities enter humans primarily through food – in particular through meat and dairy products. Therefore, food chain modelling is of utmost importance for human exposure assessment. Model comparison and quantification of uncertainties of model results are vital for their correct interpretation. This leads to the following questions: How would a model framework be structured favouring flexibility, transparency, comparability, interpretability, without limiting the capabilities of the model parts? How can carry-over modelling of chemical biotransfer into biota such as meat or milk be improved considering limited data availability and high uncertainties? How can environmental multimedia multipathway models be compared in a systematic and detailed way, and what are important sources of differences? How to identify important sources of uncertainty in a model result, including regression models used for estimation and when modelling large sets of chemicals? In order to answer that, the following specific goals are addressed: Develop a consistent matrix algebra framework for multimedia fate, multipathway exposure and toxicity effects models. Review existing biotransfer models for chemical transfer into meat and milk and develop, compare and evaluate an improved carry-over model for meat and milk. Compare selected multimedia fate, multipathway exposure and toxicity effects models on the level of final characterisation factors as well as for intermediate results. Develop and test approaches to assess the uncertainty of model results accounting for regression model uncertainty and main parameters contributing to overall uncertainty. Chapter 1 puts this dissertation into its context and introduces multimedia fate, multipathway exposure and human health and ecosystem effects modelling with a focus on the food chain exposure in the frame of comparative risk and Life Cycle Impact Assessment. Chapter 2 presents a framework for multimedia multipathway models entirely based on matrix algebra. When assessing human health or ecosystem impacts of chemicals several calculation steps need to be addressed. We suggest a matrix algebra framework which includes the fate, exposure, effect, and damage assessment for human health and ecosystems, also applicable to spatial modelling. Special emphasis is laid upon interpretation of the physical meaning of different elements within the matrices. Chapter 3 describes