Since the mid-1970s, there have been many reports that purport to implicate aluminium in the aetiology of neurodegenerative disease. After several decades of research, the role of aluminium in such disease remains controversial and is not the subject of this review. However, if aluminium is implicated in such disease then it follows that there must be a toxicological mechanism or mode of action, and many researchers have investigated various potential mechanisms including the involvement of oxidative damage, cytotoxicity and genotoxicity. This paper reviews many of the publications of studies using various salts of aluminium and various genotoxicity end points, both in vitro and in vivo, with a focus on oxidative damage. The conclusion of this review is that the majority, if not all, of the publications that report positive results have serious technical flaws and/or implausible findings and consequently should contribute little or no weight to a weight of evidence (WoE) argument. There are many high-quality, Good Laboratory Practice (GLP)-compliant genotoxicity studies, that follow relevant OECD test guidelines and the European Chemicals Agency (ECHA) integrated mutagenicity testing strategy, on several salts of aluminium; all demonstrate clear negative results for both in vitro and in vivo genotoxicity. In addition, the claim for an oxidative mode of action for aluminium can be shown to be spurious. This review concludes that there are no reliable studies that demonstrate a potential for genotoxicity, or oxidative mode of action, for aluminium.

中文翻译：

---

对铝盐基因毒理学出版物的批判性审查：1990-2018

自 1970 年代中期以来，已有许多报道声称铝与神经退行性疾病的病因有关。经过几十年的研究，铝在此类疾病中的作用仍然存在争议，因此不是本综述的主题。然而，如果铝与此类疾病有关，那么必然存在毒理学机制或作用方式，许多研究人员已经研究了各种潜在机制，包括涉及氧化损伤、细胞毒性和遗传毒性。本文回顾了许多使用各种铝盐和各种基因毒性终点的研究出版物，包括体外和体内，重点是氧化损伤。本次审查的结论是，大多数（如果不是全部），报告阳性结果的出版物中有严重的技术缺陷和/或令人难以置信的发现，因此对证据权重 (WoE) 论点的贡献很小或没有。有许多符合良好实验室规范 (GLP) 的高质量基因毒性研究，遵循相关的 OECD 测试指南和欧洲化学品管理局 (ECHA) 的综合致突变性测试策略，对几种铝盐进行测试；所有这些都显示出体外和体内遗传毒性的明显阴性结果。此外，关于铝的氧化作用方式的说法可能被证明是虚假的。这篇综述的结论是，没有可靠的研究证明铝具有潜在的遗传毒性或氧化作用方式。