ESTROGEN MODULATION - TIERED TESTING FOR HUMAN HAZARD EVALUATION

Recent concerns about the potential of certain chemicals to modulate e strogen-regulated processes have led to questions as to how chemicals should be tested for such effects, Therefore, AIHC has developed a com prehensive, resource-efficient, and flexible tiered strategy for estro gen modulation (EM) testing, Levels of evaluation include Tier 0, in w hich exposure, along with alerts based on structure-activity, persiste nce, bioaccumulation, and other data, are assessed to prioritize chemi cals for preliminary testing, In Tier I, short term in vitro, ex vivo, and/or in vivo assays are used to obtain a preliminary indication of ERI potential. Among these, an in vivo response assay is considered th e most reliable at this time, However, none of these tests are intende d for risk assessment, but rather to aid in choosing chemicals for fur ther testing and in guiding the extent of that testing, Tier II is aim ed at risk assessment and involves whole animal tests that contain EM- sensitive end points (e.g., two-generation reproduction study). Tier I II consists of hypothesis-driven research reserved for situations wher e targeted research can reduce levels of uncertainty, This tiered appr oach provides a framework for the strategic and effective application of EM test methods to address specific information needs on a case by case basis. (C) 1997 Elsevier Science Inc.