The development, validation and implementation of human systemic TEQs as biomarkers for dioxin-like compounds.

Various biochemical and molecular techniques to determine enzyme activity and gene expression changes after exposure to dioxin and dioxin-like compounds in vivo and in vitro.

Chlorinated dioxins and biphenyls (PCBs) commonly occur in the human food chain and can still be detected at levels that might cause long-term health effects. Exposure to dioxin-like compounds involves a complex mixture with a common mechanism of action involving endocrine, developmental, carcinogenic, immune and neurological effects. Risk assessment is performed with an additive model for mixture toxicity. Based on this, the Toxic Equivalency (TEQ) concept was developed as a biomarker for exposure and risk. TEQs are the sum of congener-specific toxic equivalency factors (TEFs) multiplied by the concentration in a matrix, e.g. blood. TEF values are a composite quantitative value from a range of biomarkers that are congener- and endpoint-specific. Present human TEQs have been derived from oral administration experiments providing 'intake' TEFs. Regulatory authorities frequently use 'intake' TEQs for blood and tissues considering it a biomarker for exposure or effect. Experimental evidence shows that using 'uptake' TEQs as 'systemic' biomarkers may lead to misinterpretation of risks. Therefore, development and validation of 'systemic' TEFs and TEQs as biomarkers is necessary.

The EU FP7 project SYSTEQ has as major objectives re-evaluation of the current TEQs. In order to recalculate and compare currently used 'intake' TEQs, new 'systemic' TEQs have to be established. Although there is a vast knowledge on effects of dioxin and dioxin-like compounds in a wide variety of species, data on systemic TEQs is lacking. Furthermore, many studies on dioxin and dioxin-like compounds have been performed in the late 1990's/early 2000's while advanced laboratoy techniques, especially with regard to genetic profiling, have only begun to arise in the past years. This means that gathering new data on effects of dioxin and dioxin-like compounds with respect to genomic changes and potential biomarkers is extremely important from a risk assessment point of view.

The 'systemic' TEFs and TEQs that will be calculated with the proposed experimental from SYSTEQ will be used in conjunction with results of the completed EU-funded PCBRISK project, in which two populations from Slovakia with very different exposure were studied. Individual blood levels and different biomarkers are already available. Results of SYSTEQ are also going to be used to establish international consensus values of 'systemic' TEFs at WHO level, facilitating the global use of 'systemic' TEQs as biomarkers of effect and exposure.