Since the inception of the US Environmental Protection Agency’s (EPA) Endocrine Disruptor Screening Program (EDSP), Consortium member scientists have proposed approaches to reducing the number of animals used to test the approximately 10,000 chemicals targeted by the programme. They have provided comments in response to numerous public consultations on the programme, collaborated with industry trade organisations to petition the EPA, presented at international conferences, and published articles on testing strategies for reducing animal use significantly. The EPA incorporated many of these strategies into its updated EDSP work plan, EDSP21. If carried out, this plan will avoid the use of as many as 3 million animals over the course of the programme.