Pelepenko Lauter Eston, Hewitt Benjamin, de Oliveira Rodrigo Bueno, Moraes Brenda Fornazaro, Coraça-Huber Débora C, Janini Ana Cristina Padilha, Marciano Marina Angélica
Departmento de Odontologia Restauradora, Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas (Unicamp), Avenida Limeira 901, Piracicaba, SP CEP 13414-903, Brazil; State University of Campinas (Unicamp), School of Medical Sciences, Internal Medicine Department, Nephrology Division., Cidade Universitária Zeferino Vaz, Laboratory for Evaluation of Mineral and Bone Disorders in Nephrology (LEMON), Rua Cinco de Junho, 350, Campinas, SP, 13083-033, Brazil.
Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, BirminghamB15 2TT, UK.
J Hazard Mater. 2025 Aug 15;494:138580. doi: 10.1016/j.jhazmat.2025.138580. Epub 2025 May 12.
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.
水硬性硅酸钙基材料在牙髓病学的牙科领域中被广泛使用，并且向这些材料中添加了金属射线不透光剂，以便进行影像学识别。自20世纪90年代起就已有的基于波特兰水泥的材料ProRoot MTA®中添加了氧化铋用于射线不透光目的。这种添加剂（约20%重量/重量替代）会引发关键的局部缺点，如牙本质变色、细胞毒性以及金属硫蛋白（MT1和MT2A）的基因表达上调，这表明细胞对金属的防御机制。此外，一项体内研究还表明，在动物模型中植入含铋材料后，血液和器官（肝脏、大脑和肾脏）中存在铋的积累；因此，本文提出了这些底物中铋积累的机制。为此，针对每个主题在数据库（PubMed和Embase）中进行了开放文献综述方法，重点关注氧化铋在牙本质变色机制中的相关性、其在修复性牙本质途径中缺乏有益作用、其从材料中的浸出以及在血液中的检测，以及在肝脏、大脑和——主要是——肾脏中的积累。在皮下组织和骨骼中植入30天后，这种材料在肾脏中的铋积累量分别报告为334.42和279.38 ng/g。令人担忧的是，长期植入后质量分数仍远高于未暴露的对照组。与肝脏相比，肾脏中的积累平均高出160倍。其他化合物也可作为牙科材料的射线不透光剂（即氧化钽、钨酸钙和氧化锆）。最近的研究指出，与对照组相比，氧化钽和氧化锆在肾脏中的积累模式较低。令人担忧的是，这些最近的研究分析是针对几种已上市的材料进行的，这表明制造商在产品推出前忽视了系统测试。建议进行更严格的测试。由于氧化铋似乎是最具全身安全性的射线不透光剂，本文在此介绍了每个检测到的积累部位的机制途径。
