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Press release

Health and the Environment: European research on endocrine disrupters receives major boost

 

Brussels, 15 May 2002

Key words : endocrine disrupters, wildlife, human health, environment, cluster

 


Europe's leading researchers on human health and wildlife impacts of endocrine disrupters will be brought together under a new research "cluster" supported by DG Research which is to contribute €20 million. This cluster project will provide a critical mass for new and existing research on endocrine disrupters and their effect on human health and on the environment. Endocrine disrupters are suspected of causing problems for human health and wildlife. For instance, cases have been reported of fish, frogs and alligators changing sex as a result of exposure to endocrine disrupting chemicals in polluted aquatic environments.

"This research will complement ongoing efforts to assess the risks posed by chemicals in our environment and provide a direct contribution to the European Union's Community Strategy for Endocrine Disrupters. It is essential that we base our policies and regulations on sound science and that we invest in the reinforcement of our scientific capabilities to test chemicals on possible endocrine disruptive characteristics", stated Commissioner for Research Philippe Busquin.

What are endocrine disrupters?
The endocrine system co-ordinates the activities of the organs in the body. Endocrine organs, such as the testes, ovaries, adrenal, pancreas, pituitary, thyroid and parathyroid, produce and release hormones to the bloodstream. Hormones are present in extremely low concentrations and they act in specific organs. Over the last thirty years, evidence has accumulated that a variety of chemicals, including natural and synthetic hormones (also phytoestrogens), pesticides, additives used by the plastic industry, surfactants and persistent environmental pollutants like polychlorinated aromatic hydrocarbons (eg: PCBs and dioxins) can mimic or disrupt hormone action. These types of substances are known collectively as endocrine disrupters. They can act, for example, through interference with the synthesis, secretion or action of natural hormones in the body that are responsible for the maintenance of homeostasis, reproduction, development and/or behaviour. Therefore, exposure to these substances could affect different organs in the body, with a number of harmful consequences, such as lowered sperm counts for humans or change in sex for animals.
Endocrine disrupters have been shown to disrupt the endocrine systems of animals in laboratory studies, and there is evidence that they cause developmental abnormalities and reproductive impairment in certain fish and wildlife in polluted waters. The relationship between endocrine related human malfunctions and diseases, such as cancer, and exposure to contaminants is poorly understood and has only recently being investigated in a more systematic manner. However, gaps remain in our knowledge of the mechanisms and substances involved and extensive research is needed.

European policy
European policy regarding endocrine disrupters is outlined out by the Community Strategy for Endocrine Disrupters (COM(1999)706 final), adopted by the Commission in December 1999 and supported by the Council and the Parliament, as well as by the follow-up communication on its implementation* . In its medium-term actions, the strategy identifies research and development as one of three priorities, the other two being Identification and assessment of endocrine disrupters and Identification of substitutes and voluntary initiatives.

Research
In response to this strategic need and to tackle the knowledge gap concerning these chemicals, the European Commission allocated a budget of €20 millions for research on the health and environment implications of endocrine disrupters. This dedicated call for proposals for research projects was organised jointly by the DG Research Quality of Life and Environment and Sustainable Development programmes. Following evaluation 4 excellent projects were proposed for funding and regrouped into a "cluster":

  • EDEN: Endocrine Disrupters: exploring novel end-points, exposure, low-dose and mixture-effects in humans, aquatic wildlife and laboratory animals (22 partners in 10 countries, €8.7 million EC contribution).
  • COMPRENDO: Comparative research on endocrine disrupters - Phylogenetic approach and common principles focusing on androgenic/antiandrogenic compounds (13 partners in 9 countries, €3.3 million EC contribution).
  • EURISKED: Multi-organic risk assessment of selected endocrine disrupters (10 partners in 8 countries, €3.1 million EC contribution).
  • FIRE: Risk assessment of brominated flame retardants as suspected endocrine disrupters for human and wildlife health (19 partners in 7 countries, €4.9 million EC contribution).
    For more information, see annex
This cluster co-ordinated by the EDEN project will involve 64 organisations in Europe and covers a wide range of expertise and disciplines to create the necessary "critical mass" of knowledge. The cluster is to become a point of reference of European research in this field and its activities will be open to other ongoing or future EU-funded projects in the field. Thus, the cluster approach provides an indication of the integrated project, which is a new funding instrument proposed for the Sixth Framework programme (2002-2006). Other ongoing and future projects on endocrine disrupters will also be associated with the "cluster" in a more informal way (participation at workshops etc) to further enhance the focus and co-ordination of EU research support.

An interface between scientists and policy-makers
One of the objectives of the cluster is to establish an interface between scientists and policy-makers, as this is an area with major policy and regulatory implications. For instance this initiative can contribute to the development of the new EU policy on chemicals presented in the Commission White Paper: Strategy for a Future Chemicals Policy (COM(2001)88 final)**.

For additional information:

  • Stéphane Hogan, Press Officer, DG research, european commission Tel.: +32.2.296.2965 - Fax: +32.2.295.8220
    E-mail : Research Contact

  • Tuomo Karjalainen, Scientific Officer, Quality of Life programme, DG research, european commission Tel.: +32.2.298.4660 - Fax: +32.2.296.4322
    E-mail : tuomo.karjalainen@ec.europa.eu

  • Kirsi Haavisto, Scientific Officer, Energy, Environment & Sustainable Development prog., DG research, european commission Tel.: +32-2-296.2361 - Fax: +32-2-295.2097
    E-mail : kirsi.haavisto@ec.europa.eu

* Implementation of the Community Strategy for Endocrine Disrupters (COM2001-262)
** the Commission White Paper (Strategy for a Future Chemicals Policy, COM(2001)88 final)


ANNEX:


Details on the 4 projects forming the cluster on Endocrine Disrupters

  1. EDEN: Endocrine Disrupters: Exploring novel end-points, exposure, low-dose and mixture-effects in humans, aquatic wildlife and laboratory animals.
    The project involves 22 partners from 10 countries (BE, 2CH, 3DE, 2DK, 2ES, 2FI, FR, 2NL, 2SE, 5UK), with a €8.7 million EC contribution.
    EDEN is a large integrated project addressing common problems in wildlife and human hazard assessment utilising a coherent approach. As such, the project grouping already forms a network which will be extended through the inclusion of the clustering function proposed.
    • Background: In the EU, there are significant human and wildlife health problems that stem from endocrine disruption. What is unresolved is whether human/wildlife exposure to endocrine disrupting chemicals from the environment plays any causal role in these developmental disorders. The motivation of EDEN is to meet this challenge by addressing common problems in wildlife and human hazard assessment in one coherent approach. It will produce data about the occurrence of mixed exposures to EDC in humans and fish and develop new experimental models that allow more meaningful extrapolations from animals to humans. It will produce data about low-dose- and mixture effects of EDC that are directly relevant to hazard and risk assessment. It will provide new insights into indicators of reproductive health of European citizens and will help to produce the scientific basis for a coherent strategy for dealing with EDC in the EU.
    • Work to be undertaken: EDEN has the following specific objectives:
      (i) to gather data about the composition of complex mixtures of EDC in human and fish tissues;
      (ii) to investigate the mechanisms underlying the action of EDC in order to evaluate the relevance of existing experimental models for wildlife and human hazard assessment;
      (iii) to provide new insights into indicators of impaired reproductive function in European citizens and to extend and improve existing European data bases;
      (iv) to gather data about low-dose effects of EDC;
      (v) to assess the effects of multicomponent mixtures of EDC and to investigate whether EDC produce joint effects when combined at doses below their individual effect thresholds;
      (vi) to assess how low-dose and mixture effects should be taken into consideration in testing guidelines and risk assessment procedures for wildlife and humans. The strands of the project are strongly interlinked: The work aimed at establishing the composition of EDC mixtures in human and fish tissues will provide valuable guidance for experimental mixture studies. The identification of key mechanisms and novel endpoints of EDC action will exploit modern molecular biological approaches (genomics, proteomics) to inform the work on human productive health and on low-dose- and mixture effects. These latter studies will feed into work considering how testing- and risk assessment procedures should be modified to take account of low-dose- and mixture effects of EDC.

    Contact: The School of Pharmacy, University of London, Centre for Toxicology, 29-39 Brunswick Square, London, WC1N 1AX, United Kingdom. Tel.: +44-20-77535908; Fax: +44-20-77535908; e-mail: andreas.kortenkamp@ulsop.ac.uk

  2. COMPRENDO: Comparative research on Endocrine Disrupters - Phylogenetic approach and common principles focusing on androgenic/antiandrogenic compounds
    This project involves 13 participants from 9 countries (3DE, DK, ES, FR, GR, 2IT, PL, SE, 2UK) with an EC contribution of €3.3 million.
    COMPRENDO is an interdisciplinary integrated approach addressing endocrine disruption in human and wildlife species focussed on androgenic/antiandrogenic compounds (AACs).
    • Background: The overall goal of COMPRENDO is to improve our understanding of the effects of endocrine disrupting chemicals on aquatic wildlife and humans, focussing on androgenic and antiandrogenic compounds. Until now, the greatest attention has been focussed on estrogenic effects in wildlife and humans, the only exceptions being the androgenic activities of organotin compounds in molluscs, caused by an interference with key enzymes of steroid metabolism. These compounds affect the same molecular targets in other taxa, including humans, so that androgenic and antiandrogenic compounds offer the unique opportunity to study a wildlife-human connection and to identify common principles of action across taxa which will have relevance far beyond the chosen group of compounds.
    • Work to be undertaken: The project will identify human and environmental exposures to androgenic and antiandrogenic compounds. The project will:
      (i) Quantify the human and environmental exposure to androgenic and antiandrogenic compounds by analysing representative samples of human tissues, body fluids, food products and environmental samples;
      (ii) expose a range of human-relevant models (cell lines, tissues, rodents) and aquatic organisms (amphibians, fish, echinoderms, crustaceans, molluscs) to 13 model compounds and a range of environmental samples to identify and quantify biological effects at different biological integration levels (from molecules to morphological alterations);
      (iii) establish dose/concentration-response relationships;
      (iv) establish laboratory cultures of suitable invertebrates and characterise their baseline endocrinology by measurements of steroid concentrations, receptor binding and a comparison of receptor structures;
      (v) clone a set of genes that control reproduction, development and sexual differentiation in different species and measure altered patterns of expression as a consequence of exposure to androgenic and antiandrogenic compounds

    Contact: Dr. Ulrike Schulte-Oehlmann, Johann Wolfgang Goethe-University Frankfurt, Zoological Institute, Dep. of Ecology & Evolution, Siesmayerstr. 70, 60054 Frankfurt am Main, Germany. Tel.: 49-69 79824738; fax: 49-69 79824748; e-mail: schulte-oehlmann@zoology.uni-frankfurt.de

  3. EURISKED: Multi-organic risk assessment of selected endocrine disrupters.
    This project involves 10 partners from 8 countries (AR, CH, 2DE, ES, FI, PL, SE, 2UK), with a €3.1 million EC contribution.
    • Background: Molecular and cell biological experiments as well as research in animals and in the human indicate that EDs with estrogenic actions exist, which are present in either cosmetics (such as UV-absorbers and stabilisers) or pesticides/fungicides. Little research has been done as to whether these substances interact with other steroid receptors or act in non-reproductive organs like the neuroendocrine brain, the cardiovascular, skeletal or urogenital system during development and adult life. Hence, risk assessment for organs known to be estrogen-, androgen-, progestin-, glucocorticoid- or thyroid hormone-receptive following exposure to the above mentioned endocrine disrupters cannot be made on the basis of the present data.
    • Work to be undertaken: Many diseases have been related to pre- or postnatal exposure to EDs and long-lasting effects need to be studied. EDs with steroidal or anti-steroidal effects will be studied in rats and gene-targeted mice. Dams and new born pups receive substances known to be either estrogenic or antiandrogenic or to have antithyroid hormonal effects (UV-absorbers used in the production of sunscreens, 1 stabiliser used in cosmetics, 1 fungicide used in fruit addition). Adult gonadectomised, thyroidectomised or adrenalectomised rats and gene-targeted mice will also be fed with the substances (steroid receptor knock-out mice). Estrogenic, androgenic, progestational, gucocorticoid and thyroidal effects will be studied with genomic and proteomic tools in the brain and in the cardiovascular, skeletal anduro-genital systems. Experiments with steroid-receptor knock-out mice (ER a and Beta, AR, GR and thyroid hormone receptor k.o. mice) will prove ultimately as to whether the substances of interest have steroid hormone receptor mediated activities in the intact organism.
      Clinical trials will be performed with phytoestrogens and UV absorbers. It will be easy to identify patients using phytoestrogens instead of conventional hormone replacement therapy and to study the effects of these phytoestrogens on the cardiovascular system (including the lipid profiles) and the bone. UV absorber-exposed patients will be available particularly during summer. Transdermal resorption of UV-absorbers and their temporal presence in the body may be determined in the blood using tools such as reporter cells and HPLC/UV detection.

    Contact: Prof. W. Wuttke. Division of Clinical and Experimental Endocrinology, Faculty of Medicine, University of Goettingen, Robert-Koch-Str. 40, 37073 Goettingen, Germany. Tel.: 49-551-396714; Fax: 49-551-396518;e-mail: ufkendo@med.uni-goettingen.de
     

  4. FIRE: Risk assessment of brominated flame retardants (BFRs) as suspected endocrine disrupters for human and wildlife health.
    This project involves 19 partners from 7 countries (BE CZ, 3DE, 7NL, 3NO, 3SE, UK), with a €4.9 million EC contribution.
    FIRE is an integrated multi- and interdisciplinary approach of direct toxicological studies and exposures assessments to characterise the emerging human and wildlife health risks for BFRs by endocrine disruption. The final integrated risk assessment for endocrine disrupters in humans and aquatic wildlife will be communicated to policymakers, public and industry as a basis for preventive actions.
    • Background: The project is an integrated approach of directed toxicological studies and exposure assessments to characterise the emerging human and wildlife health risks from brominated flame retardants (BFRs) such as the high production volume chemicals polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCDD). These substances are present, for example, in polyurethane foam for furniture and are targeted for regulatory action. These substances have been identified as potential endocrine disrupters. PBDE levels have been steadily increasing in biota over the last decades.
    • Work to be undertaken. The workplan consists of 7 major components:
      (i) synthesis of selected compounds and in vitro prescreening to minimise the number of animal experiments. The latter includes QSAR modeling based on in vitro data to identify possible interactions of BFRs with estrogen, androgen, progesterone, thyroid hormone and dioxin receptor, as well as possible effects on the synthesis, transport and metabolism of sex and thyroid hormones;
      (ii) toxicity studies for human hazard identification with BFRs ( selected on in vitro data) comprising subacute and 2-generation studies in rats and covering development, reproduction, sex and thyroid hormones, P450 levels, immunology, neurobehaviour and pathology of endocrine and immune organs; this part also includes toxicokinetics of TBBPA in humans;
      (iii) toxicity studies for aquatic wildlife hazard identification with BFRs (selected on in vitro data): subacute and partial life cycle tests in flounder or zebra fish, including reproduction parameters and histopathology of endocrine and immune organs, and genomics in zebrafish;
      (iv) human exposure assessment based on identification and temporal trends of BFRs in human milk, duplicate diets and various food groups in the EU;
      (v) exposure assessment based on congener specific identification, geographical variation (reference vs. polluted sites) and temporal trends of BFRs in the aquatic food chain (water, sediment, invertebrates, fish, and top predators); metabolic transformation of BFRs in wildlife and microorganisms; aquatic food web modelling. (vi) Final integrated risk assessment for endocrine effects in humans and aquatic wildlife based on data from parts 1-5;
      (vii) dissemination of knowledge.

    Contact: Prof. J. Vos, National Institute of Public Health and the Environment, Laboratory for Pathology and Immunobiology, Antonie van Leeuwenhoeklaan 9, 3720 BA Bilthoven, Netherlands. Tel.: +31-20-2742075; Fax: +31-30-2744437; e-mail: j.vos@rivm.nl
              

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