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NHR DEVTOX Résumé de rapport

Project ID: 512153
Financé au titre de: FP6-LIFESCIHEALTH
Pays: Belgium

Final Report Summary - NHR DEVTOX (A prospective analysis of the mechanisms of nuclear hormone receptors and their potential as tools for the assessment of developmental toxicity)

The ultimate aim of the NHR DEVTOX project was to produce a prospective analysis of the mechanisms of Nuclear hormone receptors (NHR) and their potential as tools for the assessment of developmental toxicity and for the development of innovative non-animal testing methods. For the development of alternatives to animal assays it was recognised in the workshops that approaches should be founded on fundamental mechanisms in order to enable more reliable inter-species extrapolation, especially to predict human hazard. The consortium noted that signalling pathways from NHR were highly conserved between species and constituted critical targets for understanding the mode of action of developmental toxicants. Consequently, the approach should lay focus on investigating the role of NHR in developmental toxicity. Furthermore, a well-developed research case example on male reproductive effects was analysed and a generic paradigm was developed and agreed that would form the basis for application of new technologies for future research. These new enabling technologies allowed investigating processes and mechanisms that were not previously possible. The molecular biology and analytical capabilities represented by these technologies such as toxicogenomic / proteomic analyses, cellular models and cell reporting assays, continued to develop rapidly and allowed the development of new possibilities and approaches.

There was a general agreement that the areas for research should be determined based on the most common and important clinical effects. One approach proposed was to examine epidemiology data on developmental abnormalities for correlation with hormones. A debate on some specific areas resulted in the fact that the focus should be laid on clinical findings of concern that were relevant to human health and should be feasible. Organ systems considered to be of potential value for such research including the urinogenital, respiratory, musculoskeletal, circulatory and immune systems.

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