Endocrine Abstracts

Endocrine disrupting chemicals (EDCs) harm human health both as single molecules and as mixtures. Most research on EDCs is done on individual chemicals whereas we are exposed to mixtures of numerous and possibly interacting molecules. This discrepancy presents a dilemma for risk assessment and legislation. Thyroid hormones are essential for normal brain development where they influence, through specific embryonic and post-natal periods all the steps of brain development. In adults, TH roles are essential to brain function and to general metabolism (thermogenesis, fat burning, etc.). As number of compounds produced by chemical industries increased by 300 fold since the 70’s, and many reports in the scientific literature show that many of these chemicals are potential Endocrine disruptors (EDCs) we questioned the thyroid hormone disrupting effect of common chemicals. We hypothesized that this axis could be a key target for disruption and hence alter normal brain development. To test this hypothesis, we used a thyroid disruptor screening assay, the Xenopus Embryonic Thyroid Assay (XETA), RT-qPCR on brain tissue, and behavior analysis. We used to independent strategies with different mixtures from human data. First we recreated m a mixture of 15 compounds commonly found in Human beings and tested them at the concentration meassured in amniotic fluid and study the effects on thyroid hormone signaling and adverse effects on our tadpole model. Second, a novel approach, developed within the European project, EDC-MixRisk, was to classify adverse mixtures of chemicals found in population based on epidemiological studies and test their EDC potential with both in vivo and in vitro assays. Samples from about 2,000 pregnant women were examined and retrospective analysis on offspring identified a chemical mixture for which embryonic exposure was associated with language delay, an indication for neurodevelopmental delay. Results on the two kind of mixtures show significant modification of TH availability (XETA assay) at the actual mixture concentration found in fluids of pregnant women. Second, mRNA levels of key genes involved the TH-signaling pathway showed significant alteration of TH-dependent genes at the accrual exposure level. Finally, mixtures were found to alter tadpoles’mobility behavior. Taken together, these results show advantages of using different strategies and necessity to take into consideration mixture in both experimental studies and risk assessment.