1999Symposium

Herman B.W.M. Koeter
Environmental Health and Safety Division
OECD, Paris, France

Since the mid 1990s the international concern about the potential of chemicals to disturb the endocrine system of both humans and wildlife populations have been growing increasingly and numerous industrialised countries have started national activities to further investigate and assess this problem. In order to avoid major differences in national policies with respect to the regulation of endocrine disrupting chemicals, OECD has started a Special Activity to co-ordinate the work internationally. The objectives of the OECD Endocrine Disruptors Activity are to: i) provide information and co-ordinate activities, ii) develop new and revise existing test Guidelines to detect endocrine disruptors, and iii) harmonise hazard and risk characterisation and assessment approaches for endocrine Disruptors among Member countries. These objectives are in full agreement with recommendations from the IFCS (Intergovernmental Forum on Chemical Safety) for work to be carried out by IOMC (Inter-organisation Programme for the Sound Management of Chemicals).

First a Detailed Review Paper (DRP) was developed which provided a state-of-the-art overview of testing methods in this field. In addition, to the DRP, a questionnaire on the concern and national activities with respect to endocrine Disruptors was developed and circulated to the Member countries in December 1996. Responses were received from 21 countries and subsequently. It appeared that in half of the countries endocrine Disruptors are a major concern, other countries considered it a concern but not of utmost importance. Countries expressed caution with respect to the identification of the most appropriate endpoints for hazard characterisation: time is needed for scientific review of available methodology and for the validation of selected test methods. The reproductive organ systems in mammals and aquatic species, including hormone determinations were considered the most relevant endpoints. The need to revise existing Test Guidelines was frequently mentioned. The DRP also stressed the need for transparency with respect to the selection of most promising (screening) tests and for full validation of selected methods. Two workshops, co-organised by OECD with others, were held in Weybridge, UK (December 1996) and Veldhoven, the Netherlands (April 1997). They came up with similar results and recommendations.

In December 1997, the OECD established a Working Group on Endocrine Disruptors Testing and Assessment (EDTA). The EDTA with participation of Member countries, European Commission (EC), IPCS, WWF, industry and labour organisations met for the first time in March 1998. The objectives of the first meeting were to: (i) identify and prioritise enhancements and modifications to existing Test Guidelines, (ii) identify and prioritise new Test Guideline needs, (iii) develop a workplan for the updating of existing and the development of new Test Guidelines, including validation work as appropriate, and, (iv) develop a harmonised testing strategy for the screening and testing of endocrine disruptors. The EDTA Working Group discussed the following testing strategies, considered as most relevant: (i) the Proposed Model Testing Strategy as recommended by the "Weybridge" workshop, (ii) the Proposed Hazard Identification Scheme, recommended by the "Veldhoven" workshop, and (iii) the US EDSTAC (Endocrine Disruptors Screening and Testing Advisory Committee) Conceptual Framework. The EDTA Working Group reached agreement on an Initial Framework for the Testing of Endocrine Disrupting Substances which is based on three levels. The first level comprises an initial assessment and no testing is involved at this level. Based on existing information, including physical-chemical data, QSAR's, exposure estimations and available toxicological data, a decision is made on further work. The next level comprises screening. The purpose of the screening would be to set priorities for more in-depth studies and to study mechanisms of action. Both in vivo and in vitro assays are considered at this level. The third level is subdivided into hazard identification/characterisation testing and, finally, definitive testing. The latter includes a full two-generation reproductive toxicity study, sufficiently enhanced to cover endpoints specifically sensitive to endocrine disruptors. At this level also an aquatic environmental toxicity study (most likely in fish) is considered. The former includes a series of mammalian tests covering in utero exposure, the growing-up phase and the mature animal. With respect to the environment tests in birds and amphibians are considered. The EDTA Working Group also made recommendations as to the endpoints which need to be included in the various existing Test Guidelines to sufficiently enhance these tests for use in endocrine Disruptors testing.

A major activity which is currently being initiated is the validation of (screening) tests, which are currently recommended. The EDTA Working Group reached consensus on the approach for validation, taking into account the principles and criteria as established by OECD based on the outcome and recommendations of a Workshop held in Solna, Sweden in January 1996. These principles and criteria are also adopted by the US and the European Union. Validation testing will start soon in Europe, Japan, Korea and the US. The same small series of chemicals which are identified as strong and weak endocrine disruptors will be used in all three regions and Management Committees will be established to oversee and co-ordinate the activities.

Endocrine Disruptors: Global Research And Policy Issues In OECD Member Countries