Oller Adriana R, Heim Katherine, Brouwers Tony, Barroso João, Prieto Pilar, Viegas Vanessa, Verougstraete Violaine T
Oller Consulting, 722 Gaston Manor Dr, Durham, NC, 27703, USA.
NiPERA, 2525 Meridian Parkway, Suite 240, Durham, NC, 27713, USA.
Arch Toxicol. 2025 Aug;99(8):3283-3296. doi: 10.1007/s00204-025-04024-0. Epub 2025 Jun 18.
When matrix effects are present in alloys, the content of the metal ingredients is no longer reliable to predict the metal ion release and hence toxicity. Thus, the metals' industry proposed an alternative concept for self-classification based on the comparison of the metal releases between alloys and their ingredients; this approach better reflects the toxicity of the alloys when matrix effects are present. Samples of alloy and ingredients (reference) often differ in particle size. This study assessed the impact of particle sizes on cobalt (Co) and nickel (Ni) releases from different particle size fractions of an alloy powder, following a bioelution gastric fluid protocol. Results were considered together with those from reference pure Co and Ni powders. Co-release per gram of alloy increased (3- to 4-fold) when median particle diameter decreased (17-fold). For Ni, the releases were much lower, but the relative increases with decreasing particle diameter were greater (38-fold). Results from the < 100 µm fraction were lower than those for the fraction matching the particle size of the reference samples (by 2.1-fold for Co and 7.6-fold for Ni) but were higher (by 1.2-fold for Co and 2.0-fold for Ni) than those from the sample on the market. For all fractions, an alloy matrix effect lowering metal releases was evident. Based on the above results, we made particle size recommendations when testing alloy powders in a surrogate gastric fluid protocol relevant to the oral route of exposure. Our work provides guidance for testing alloy powders to generate data relevant to hazard self-classification.
当合金中存在基体效应时，金属成分的含量就不再能够可靠地预测金属离子的释放以及由此产生的毒性。因此，金属行业提出了一种基于合金与其成分之间金属释放量比较的自我分类替代概念；当存在基体效应时，这种方法能更好地反映合金的毒性。合金样品和成分（参考）的粒径通常存在差异。本研究按照生物洗脱胃液方案，评估了粒径对合金粉末不同粒径级分中钴（Co）和镍（Ni）释放的影响。研究结果与参考纯Co和Ni粉末的结果一同进行了考量。当平均粒径减小（17倍）时，每克合金的Co释放量增加（3至4倍）。对于Ni，释放量要低得多，但随着粒径减小的相对增加幅度更大（38倍）。<100 µm级分的结果低于与参考样品粒径匹配的级分（Co低2.1倍，Ni低7.6倍），但高于市售样品（Co高1.2倍，Ni高2.0倍）。对于所有级分，合金基体效应降低金属释放是明显的。基于上述结果，我们在与经口暴露途径相关的替代胃液方案中测试合金粉末时提出了粒径建议。我们的工作为测试合金粉末以生成与危害自我分类相关的数据提供了指导。
