Wiemann Martin, Sauer Ursula G, Vennemann Antje, Bäcker Sandra, Keller Johannes-Georg, Ma-Hock Lan, Wohlleben Wendel, Landsiedel Robert
IBR R&D gGmbH Institute for Lung Health, Mendelstr. 11, 48149 Münster, Germany.
Scientific Consultancy-Animal Welfare, 85579 Neubiberg, Germany.
Nanomaterials (Basel). 2018 Mar 13;8(3):160. doi: 10.3390/nano8030160.
In vitro prediction of inflammatory lung effects of well-dispersed nanomaterials is challenging. Here, the in vitro effects of four colloidal amorphous SiO₂ nanomaterials that differed only by their primary particle size (9, 15, 30, and 55 nm) were analyzed using the rat NR8383 alveolar macrophage (AM) assay. Data were compared to effects of single doses of 15 nm and 55 nm SiO₂ intratracheally instilled in rat lungs. In vitro, all four elicited the release of concentration-dependent lactate dehydrogenase, β-glucuronidase, and tumor necrosis factor alpha, and the two smaller materials also released H₂O₂. All effects were size-dependent. Since the colloidal SiO₂ remained well-dispersed in serum-free in vitro conditions, effective particle concentrations reaching the cells were estimated using different models. Evaluating the effective concentration-based in vitro effects using the Decision-making framework for the grouping and testing of nanomaterials, all four nanomaterials were assigned as "active." This assignment and the size dependency of effects were consistent with the outcomes of intratracheal instillation studies and available short-term rat inhalation data for 15 nm SiO₂. The study confirms the applicability of the NR8383 AM assay to assessing colloidal SiO₂ but underlines the need to estimate and consider the effective concentration of such well-dispersed test materials.
预测分散良好的纳米材料对肺部的炎症影响具有挑战性。在此，我们使用大鼠NR8383肺泡巨噬细胞（AM）试验分析了四种仅初级粒径不同（9、15、30和55纳米）的胶体无定形SiO₂纳米材料的体外效应。将数据与经气管内注入大鼠肺部的单剂量15纳米和55纳米SiO₂的效应进行比较。在体外，所有四种材料均引起浓度依赖性乳酸脱氢酶、β-葡萄糖醛酸酶和肿瘤坏死因子α的释放，两种较小的材料还释放H₂O₂。所有效应均与粒径有关。由于胶体SiO₂在无血清体外条件下保持良好分散，因此使用不同模型估算了到达细胞的有效颗粒浓度。使用纳米材料分组和测试决策框架评估基于有效浓度的体外效应，所有四种纳米材料均被归类为“活性”。这一归类以及效应的粒径依赖性与气管内注入研究结果以及15纳米SiO₂的现有短期大鼠吸入数据一致。该研究证实了NR8383 AM试验在评估胶体SiO₂方面的适用性，但强调了估算并考虑此类分散良好的测试材料有效浓度的必要性。
