REVIEW ARTICLE An integrative review on the toxicity of Bisphenol A (BPA) released from resin composites used in dentistry Lígia Lopes-Rocha 1,2 | Lara Ribeiro-Gonçalves 1 | Bruno Henriques 3,4 | Mutlu Özcan 5 | Maria Elizabeth Tiritan 2,6 | Júlio C. M. Souza 1,4 1 Department of Dental Sciences, University Institute of Health Sciences (IUCS), CESPU, Gandra, PRD, Portugal 2 Institute for Research and Advanced Training in Health Sciences and Technologies (IINFACTS), CESPU, Gandra PRD, Portugal 3 Ceramic and Composite Materials Research Group (CERMAT), Dept. of Mechanical Engineering (EMC), Federal University of Santa Catarina (UFSC), Florian opolis, Brazil 4 Centre for Microelectromechanical Systems (CMEMS-UMINHO), University of Minho, Campus Azurém, Guimar~ aes, Braga, Portugal 5 Division of Dental Biomaterials, Clinic for Reconstructive Dentistry, Center of Dental Medicine, University of Zürich, Zürich, Switzerland 6 Laboratory of Organic and Pharmaceutical Chemistry (LQOF), Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal Correspondence Júlio C. M. Souza, Centre for Microelectromechanical Systems (CMEMS), University of Minho, Campus Azurém, Guimar~ aes 4800-058, Portugal. Email: jsouza@dem.uminho.pt Funding information Fundaç~ ao para a Ciência e a Tecnologia (FCT), Portugal, Grant/Award Number: POCI- 01-0145-FEDER-031035_LaserMULTICER Abstract The main aim of this study was to perform an integrative review on the release of bisphenol A (BPA) from resin-matrix composites and potential toxic effects. A biblio- graphic search was performed on the PubMed platform using the following keywords: “Bisphenol A" OR “BPA” AND “resin composite” OR “composite resin” AND “toxicity” OR “cytotoxicity” OR “release”. Inclusion criteria involved in vitro and in vivo studies on the release and toxicity of BPA. Results highlighted the release of BPA from resin- matrix composites due to insufficient polymerization and/or degradation of the poly- meric matrix. BPA is part of the organic matrix of resin-matrix composites and may be hydrolysed in human saliva, although studies report that low doses might not be detected by traditional chemical analysis. Studies exposing zebrafish embryos to differ- ent concentrations of Bis-GMA, showed 55% mortality at 10 μM Bis-GMA while 30% mortality was recorded at 1 μM Bis-GMA. In patients, a BPA concentration of around 2.09 × 10 -2 μg/ml was found in the saliva after placement of lingual orthodontic retainers with resin-matrix composites. Also, the BPA molecule can be swallowed and absorbed by the oral/gastrointestinal mucosa, which might result in systemic toxicity. The degradation of resin-matrix composites and release of BPA in oral environment are dependent on the organic matrix content and on the polymerization method. A increased release of BPA can lead to the absorption into oral and gastrointestinal mucosa with high risks of local and systemic toxicity. KEYWORDS bisphenol A, BPA, cytotoxicity, resin composite, toxicity 1 | INTRODUCTION Bisphenol A (BPA) is an organic compound, which is used in the syn- thesis of polycarbonate-, epoxy-, and methacrylate-matrix materials utilized in several industrial and health fields. 1,2 Resin-matrix com- posites used in dentistry have BPA derivatives in their organic- matrix composition such as Bisphenol A-Diglycidyl Methacrylate (Bis-GMA), Bisphenol A-Dimethacrylate (Bis-DMA), Ethoxylated Bisphenol A Glycol Methacrylate (Bis-EMA), Propoxylated Bisphenol A-Dimethacrylate (Bis-PMA), Bisphenol A Diglycidil-Ether (BADGE), Polycarbonate-modified Bis-GMA (PC Bis-GMA), and Bisphenol A Polyethoxy Methacrylate (Bis-MPEPP). 3 The content of Bis-GMA can range from 5 up to 20wt% while Bis-EMA can range from 1 up to 5wt% and Bis-MPEPP between 5 and 10wt%. 4,5 Although the popularity of resin-matrix composites has increased in recent years, a concern on the release of toxic molecules such as BPA and its derivatives has gathered attention by scientists, clinicians, and patients. 2,4,5 After light curing, the release of methacrylate monomers from resin-matrix composites occurs mainly within the first 24 h and may Received: 3 November 2020 Revised: 2 March 2021 Accepted: 28 March 2021 DOI: 10.1002/jbm.b.34843 1942 © 2021 Wiley Periodicals LLC. J Biomed Mater Res. 2021;109:1942–1952. wileyonlinelibrary.com/journal/jbmb