Background Environmental and health problems related to endocrine disruption have increased in recent decades. Abnormalities in the reproductive system of various aquatic species (fish, molluscs, amphibians, reptiles) as well as human fertility have been linked to chemical pollution threats. Key aims of the EU’s REACH Regulation include improving awareness of the risks associated with particular chemicals and ensuring that industry is able to assess hazards and identify and implement appropriate risk management measures to protect humans and the environment. In particular, the introduction of suitable alternatives should allow the progressive substitution of the most dangerous chemicals. Test programmes within REACH do not include specific tests for endocrine-disrupting properties because there are no internationally agreed methodologies or criteria available (ECHA Guidance for Substances of Very High Concern [SVHC]). Objectives The LIFE EDESIA project aims to contribute to improved implementation of the REACH Regulation by providing at least one suitable alternative for bisphenol A/BPA, phthalates and parabens. Anticipated applications of the alternatives will include hard plastics, PVC-based medical devices for phthalates, and antimicrobials (personal care products and over-the-counter drugs) for parabens. The potential alternatives will be tested for absence of mutagenicity/genotoxicity and persistence/bioaccumulation by (Q)SAR; the in vitro tests will provide a comprehensive screen for endocrine-disrupting properties, in order to implement REACH attention toward EDCs as ‘substances of equivalent concern’. These objectives will be achieved by the following actions: Applying the substitution principle to EDCs of ‘equivalent concern’, on the basis of i) endocrine disruption effects, ii) high production volume, iii) widespread use, and iv) potential exposure of general population to SVHCs, namely: phthalates, bisphenols and parabens; Demonstrating a new, robust and cost-effective in silico/in vitro approach to evaluate suitable chemicals for replacing EDCs of equivalent concern, that can support the application of the REACH legislative framework on the substitution principle environment; Identifying potential substitutive chemicals using both emerging and existing in silico approaches; Performing a comparative assessment of the different potential substitutive chemicals using the in silico approach; Synthesising the selected substitutive chemicals; Creating prototypes that use the substitutive chemicals, and to assess them for release of chemicals; and Demonstrating the feasibility of the substitution of the EDCs considered in the project in industrial applications. Expected results: Anticipated outcomes from the project activities will include: A list of some 15 REACH-compliant potential substitutive chemicals for parabens, bisphenol A and phthalates (between three and five potential substitutes for each chemical class are envisaged); A step-wise system of in silico / in vitro integration and cross-validation for EDC substitute chemicals assessment, in compliance with REACH legislation; A report on the potential use of the chemical substitutes for EDCs for industrial purposes (medical devices, cosmetics and food packaging); and Two seminars at the European Chemical Agency/ECHA and European Food Safety Agency/EFSA to promote mainstreaming of the project’s findings at EU level.