Uncertainties in risk assessment of dioxin-like compounds : A focus on systemic relative potencies and species differences

This thesis describes experimental work undertaken to reduce uncertainties in the risk assessment of dioxin-like compounds. The toxic equivalency factor (TEF) approach is the most commonly used method for assessing the risk of complex mixtures of dioxin-like compounds. Consequently, accurate estimates of TEF values are crucial for human risk assessment. The TEF-concept is mainly based on animal experiments with oral dosage as the principal route of exposure, but human risk assessment is often assessed based on systemic (plasma) concentration. The major objectives of this thesis were to establish if there is a need for development of specific “systemic” TEFs and to evaluate whether there are consistent species-specific differences in relative potencies. The research described in this thesis shows that for some congeners the current TEF might under- or over- estimate the risk for humans based on plasma concentrations. This is due to either congener-specific toxicokinetics or species differences in response. Taking these congener- and species- specific differences into account can help to improve human risk assessment of dioxin-like compounds.