Advancing the safety assessment of chemicals without the use of animal testing Proposals should consider integrative approaches that build on advances in all relevant fields of science and technology, including elements such as novel in vitro[[This may include animal-derived material]] and in silico tools and the understanding of human biology and related toxicity pathways, with the aim of proposing and demonstrating scientifically valid means for comprehensive safety assessment of chemical substances without resorting to animal testing. Priority should be on systemic health effects in humans. Exploitation of qualitative and quantitative information and knowhow from animal, clinical, epidemiological, exposure and biomonitoring studies is encouraged where appropriate to inform research strategies and to establish the scientific credibility of the approaches proposed for relevant decision-making contexts. In addition, attention should be given to establishing and pursuing concrete measures to seek acceptance and uptake by end-users striving to address safety assessment challenges in support of product development and addressing regulatory information requirements.Proposals could consider the involvement of the European Commission's Joint Research Centre (JRC) to provide add-value regarding such aspects as supporting validation of emerging approaches, promotion of research results, and the interfacing with the regulatory community. In this respect, the JRC is open to collaborate with any successful proposal after the selection process has been completed.As a way to facilitate progress and to accelerate the harmonisation, acceptance and promotion of new approaches worldwide, applicants are encouraged to seek cooperation with industry and collaboration with any relevant complementary initiatives as well as with regulatory bodies.The Commission considers that proposals requesting a contribution from the EU of between EUR 10 and 20 million would allow this specific challenge to be addressed appropriately. Nonetheless, this does not preclude submission and selection of proposals requesting other amounts. The reliability and relevance of animal studies to support chemical safety assessment are subject to increasing scrutiny from a scientific perspective and raises broader societal concerns. To address these challenges, the European Commission has been supporting the development and application of animal-free approaches to toxicological profiling of chemicals in support of chemical safety assessment. However, significant challenges remain regarding the provision of viable animal-free solutions to address systemic health effects in humans potentially linked to chronic exposure to chemicals across a variety of regulated sectors. Consequently, further efforts are needed to progress on the development, validation and translation of scientifically sound methods that not only decrease the reliance on animal testing but which also deliver more relevant, reliable and cost-effective means to facilitate decision-making to support regulation, innovation and competitiveness. Scientifically sound, practicably implementable non-animal solutions readily deployable to aid in meaningful safety assessment of chemicals.Recognition from regulatory bodies and their engagement to translate results, methods and solutions into safety assessment practice.Uptake and commercial exploitation of the developed safety assessment approaches, products and services.Contribution to the Three Rs (3Rs) principles (‘Replacement’, ‘Reduction’, ‘Refinement’), with a particular emphasis on the ‘Replacement’ opportunities.