This review aimed to examine the potential cytotoxicity and endocrine-disrupting effects of materials used in removable orthodontic retainers. A systematic survey of the literature from 2015 to 2025 analyzed studies evaluating in vitro cytotoxicity, estrogenic activity, in vivo tissue reactions, and clinical biomarker responses. Materials assessed included PMMA plates, thermoplastic foils, fiber-reinforced composites, PEEK, and 3D-printed photopolymer resins. Forty-eight studies (38 in vitro, 10 clinical) fulfilled the inclusion criteria. Photopolymer resins were associated with the greatest cytotoxic responses, whereas PMMA and thermoplastics generally showed mild effects, which were further reduced after 24 hours of water immersion. Release of bisphenol-like compounds was observed, although systemic exposure remained within regulatory safety limits. Clinical evaluations reported no significant mucosal changes or measurable endocrine disturbances. Overall, removable retainer materials demonstrate acceptable biocompatibility, but evidence regarding long-term endocrine consequences is limited. Standardized testing frameworks are needed to allow consistent comparison across orthodontic materials. Furthermore, single-use thermoplastics may contribute to microplastic pollution and pose challenges for disposal, raising environmental sustainability concerns.
