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Endocrine Disrupting Ability of Environmental Pollutants

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.

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

Participants (7)

Bourgas Technological University
Bulgaria
Address
1,Yakimov Street
8010 Bourgas
Consorzio Milano Ricerche
Italy
Address
Via Ampere 56
20131 Milano
Karolinska Institute
Sweden
Address
7,Haelsovägen 7
141 57 Huddinge
Landbouwuniversiteit Wageningen
Netherlands
Address
5,Tuinlaan
6703 HE Wageningen
Ministry of Agriculture, Fisheries and Food
United Kingdom
Address
Remembrance Avenue
CM0 8HA Burnham-on-crouch
UNIVERSITÀ DEGLI STUDI DELLA TUSCIA
Italy
Address
Via S. Camillo De Lellis
01100 Viterbo
UTRECHT UNIVERSITY
Netherlands
Address
50,Yalelaan 2
3584 CL Utrecht