A hierarchical approach to the evaluation of chemicals for estrogenic and other endocrine-disrupting properties

The emergence of estrogenicity/endocrine-disruption as an important endpoint in the toxicological assessment of chemicals presents a series of problems to overcome before regulatory control of such agents can be enacted. A framework is presented by which progress in this endeavour can be expedited. A hierarchial approach to testing is proposed, together with consideration of the types of information required to transform test data into human risk estimations. The approach is based broadly on current methods for defining potential human carcinogens and mutagens, and if found acceptable, would dramatically accelerate regulatory progress on this subject. However, several questions must be answered, using focused data, before the approach can be endorsed or transferred into a regulatory context. The importance of early consideration of all aspects of this complex new toxicity, including the unexpected observation of synergism between synthetic estrogens, is emphasized.