Objective The main objectives of this proposal are: I. To develop and apply QSAR techniques and models for the screening of HPVCs for their binding affinity to estrogen, androgen and thyroid hormone receptors, based on the existing experimental data; II. Develop and implement an in vitro and in vivo testing strategy for endocrine disrupting chemicals; III. T o establish a list of potential endocrine disrupting chemicals. ADVANCES EXPECTED QSAR Model Development and Validation The major drawback of employing classical Linear Free Energy Relationship (LFER) based QSARs to model specific receptor binding activity is the classical QSARs limited applicability to congeneric series of molecules. A multitude of seemingly very different chemical structures can exert similar biological effects via the same mecheanisms of action, e.g. through binding to particular receptor. The project will therefore develop models capable of identifying those molecular characteristics, across structurally different classes of chemicals, that result in similar biological activity. Testing Strategy The QSAR models developed will be used to screen the chemicals from the EINECS and thereby identify potential endocrine disrupters, thus, providing a scheme for prioritization for detailed in vitro and in vivo toxicological investigations. Through the implementation of the testing strategy it is expected that current test methods will be further validated and further developed and provide a better understanding of the underlying mechanisms leading to the disruption of the endocrine system. Selection of Potential Endocrine Disrupting Chemicals It is expected that a list of potential endocrine disrupting chemicals developed in a scientifically sound manner, employing expert systems, QSAR models and in vitro and in vivo toxicological testing, can be used by the authorities of the EU Member States and the Commission to select substances of high priority for in-depth investigation through risk assessment and finally to better evaluate the risks of such substances posed to man and the environment due to their endocrine disrupting ability. Fields of science natural sciencescomputer and information sciencesartificial intelligenceexpert systemsmedical and health sciencesclinical medicineendocrinology Programme(s) FP4-ENV 2C - Specific programme of research and technological development in the field of environment and climate, 1994-1998 Topic(s) 02020101 - Risks to human health Call for proposal Data not available Funding Scheme CSC - Cost-sharing contracts Coordinator European Communities - Commission of the European Communities - Joint Research centre Address Via e. fermi 1 21020 Ispra Italy See on map EU contribution € 0,00 Participants (7) Sort alphabetically Sort by EU Contribution Expand all Collapse all Bourgas Technological University Bulgaria EU contribution € 0,00 Address 1,yakimov street 8010 Bourgas See on map Consorzio Milano Ricerche Italy EU contribution € 0,00 Address Via ampere 56 20131 Milano See on map Karolinska Institute Sweden EU contribution € 0,00 Address 7,haelsovägen 7 141 57 Huddinge See on map Landbouwuniversiteit Wageningen Netherlands EU contribution € 0,00 Address 5,tuinlaan 6703 HE Wageningen See on map Ministry of Agriculture, Fisheries and Food United Kingdom EU contribution € 0,00 Address Remembrance avenue CM0 8HA Burnham-on-crouch See on map UNIVERSITÀ DEGLI STUDI DELLA TUSCIA Italy EU contribution € 0,00 Address Via s. camillo de lellis 01100 Viterbo See on map UTRECHT UNIVERSITY Netherlands EU contribution € 0,00 Address 50,yalelaan 2 3584 CL Utrecht See on map
