Bismuth release from endodontic materials: Proposed mechanisms for systemic circulation and organ accumulation

Hydraulic calcium silicate-based materials are widely used in the dental field of Endodontics and metallic radiopacifiers are added to these materials enabling imageology identification. Bismuth oxide was added in ProRoot MTA®, a Portland cement-based material available since the 90's, for radiopacifying purposes. This additive (around 20 % weight/weight replacement) elicits crucial local drawbacks such as dentine discolouration, cytotoxicity and gene expression upregulation of metallothioneins (MT1 and MT2A), which indicates a defensive cellular mechanism against metals. Besides, an in vivo study also indicated the presence of bismuth in blood and organs accumulation (liver, brain and kidney) after bismuth-containing materials implantations in an animal model; thus, mechanisms of bismuth accumulation are here proposed for these substrates. For this purpose, an open literature review methodology in databases (PubMed and Embase) was performed for each topic focusing on relevance of bismuth oxide in mechanisms of dentine discolouration, its lack of beneficial role within reparative dentine pathways, its leaching from the material and detection in blood, and accumulation in liver, brain and - mainly - in the kidney. The accumulation of bismuth on kidney from this material was reported as 334.42 and 279.38 ng/g, after 30 days of implantation in subcutaneous tissue and bone, respectively. Worryingly, after long-term implantation mass fractions were still considerably higher than non-exposed controls. Kidney accumulation represented a 160-fold average higher accumulation in comparison with the liver. Other chemical compounds are available as radiopacifiers (i.e., tantalum oxide, calcium tungstate and zirconium oxide) for dental materials. Recent studies pointed out tantalum oxide and zirconium oxide with lower accumulative pattern in the kidneys when compared to controls. Worryingly, these recent studies analyses were performed with several already marketed materials indicating a disregard from the manufacturers towards systemic testing prior to product launching. A stricter testing is advised. As bismuth oxide appeared to be the most systemically unsafe radiopacifier, mechanistic pathways for each site of detected accumulation are here presented.