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In the matter of chemicals in the food chain, the European Union (EU) has established one of the most sophisticated and robust regulatory frameworks to ensure food safety and balance consumer protection with scientific advancements and industry needs. This review provides a holistic analysis of the EU chemical food safety scenario, examining its regulatory framework, key risk assessment methodologies, and the roles of critical institutions involved in monitoring, enforcement, and policymaking. The new and evolving challenges of chemical food safety, including transparency, cumulative risk assessment, and emerging contaminants, were discussed. Special attention is given to major classes of chemical substances in food, their regulatory oversight, and the scientific principles guiding their assessment, as well as to the role of key actors, including regulatory agencies, official laboratories, and competent authorities. This work offers an updated and integrated analysis of chemical food safety in the EU, uniquely combining regulatory, scientific, and enforcement perspectives and providing a structured roadmap for future directions.<\/jats:p>","DOI":"10.3390\/foods14091628","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T04:59:37Z","timestamp":1746421177000},"page":"1628","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Chemical Food Safety in Europe Under the Spotlight: Principles, Regulatory Framework and Roadmap for Future Directions"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1435-4390","authenticated-orcid":false,"given":"Teresa","family":"D\u2019Amore","sequence":"first","affiliation":[{"name":"Laboratory of Preclinical and Translational Research, IRCCS CROB, Centro di Riferimento Oncologico della Basilicata, 85028 Rionero in Vulture, Italy"},{"name":"Department of Pharmacy, University of Naples Federico II, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8839-7377","authenticated-orcid":false,"given":"Slim","family":"Smaoui","sequence":"additional","affiliation":[{"name":"Laboratory of Microbial, Enzymatic Biotechnology, and Biomolecules (LBMEB), Center of Biotechnology of Sfax, University of Sfax-Tunisia, Sfax 3029, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3927-9056","authenticated-orcid":false,"given":"Theodoros","family":"Varzakas","sequence":"additional","affiliation":[{"name":"Department of Food Science and Technology, University of the Peloponnese, Antikalamos, 24100 Kalamata, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.bj.2018.03.003","article-title":"Food Safety in the 21st Century","volume":"41","author":"Fung","year":"2018","journal-title":"Biomed. 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