In 1996 provisions were added to the Food Quality Protection Act and the Safe Drinking Water Act to require chemical screening for potential endocrine effects. The framework developed to accomplish these requirements is called the Endocrine Disruptor Screening Program (EDSP). Pesticide registrants are required to conduct studies of a higher tier than the EDSP Tier I battery under the Federal Insecticide, Fungicide and Rodenticide Act for the purpose of identifying potential reproductive effects. Validation of all studies employed in the EDSP is imperative so the results are reliable, and further there must be consistent application of objective criteria for the EDSP Tier I battery, including the use of scientifically appropriate interpretation of these data in order to meet requirements of the Information Quality Act. The Environmental Protection Agency (EPA) should be explicit in its indication of the limitations on the interpretation of EDSP Tier I test results. Data suggesting endocrine-related activity must be viewed in the appropriate context, e.g. is it transient or reversible and therefore not necessarily adverse. It should not be interpreted on its own as evidence of adverse effects. When conducting safety assessments the EPA should use “weight-of-the-evidence” methodology to consider all relevant information as opposed to reliance on unique and non-repeatable data. While there have been efforts by the US and other countries over the past two decades from the standpoint of assessment of chemical safety, no comparable attempts to harmonize and mutually accept testing strategies and decision-making criteria for chemicals undergoing EDSP screening has occurred. Considering the unique requirements and endpoints necessary to assess endocrine potential, development of standardized programs based on scientifically valid data and appropriate endpoints will take additional time and effort for advancement of uniform safety evaluation procedures.