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Retained particle surface area dose drives inflammation in rat lungs following acute, subacute, and subchronic inhalation of nanomaterials
Particle and Fibre Toxicology ( IF 10 ) Pub Date : 2021-08-05 , DOI: 10.1186/s12989-021-00419-w
Frédéric Cosnier 1 , Carole Seidel 1 , Sarah Valentino 1 , Otmar Schmid 2, 3 , Sébastien Bau 1 , Ulla Vogel 4, 5 , Jérôme Devoy 1 , Laurent Gaté 1
Affiliation  

An important aspect of nanomaterial (NM) risk assessment is establishing relationships between physicochemical properties and key events governing the toxicological pathway leading to adverse outcomes. The difficulty of NM grouping can be simplified if the most toxicologically relevant dose metric is used to assess the toxicological dose-response. Here, we thoroughly investigated the relationship between acute and chronic inflammation (based on polymorphonuclear neutrophil influx (% PMN) in lung bronchoalveolar lavage) and the retained surface area in the lung. Inhalation studies were performed in rats with three classes of NMs: titanium dioxides (TiO2) and carbon blacks (CB) as poorly soluble particles of low toxicity (PSLT), and multiwall carbon nanotubes (MWCNTs). We compared our results to published data from nearly 30 rigorously selected articles. This analysis combined data specially generated for this work on three benchmark materials - TiO2 P25, the CB Printex-90 and the MWCNT MWNT-7 - following subacute (4-week) inhalation with published data relating to acute (1-week) to subchronic (13-week) inhalation exposure to the classes of NMs considered. Short and long post-exposure recovery times (immediately after exposure up to more than 6 months) allowed us to examine both acute and chronic inflammation. A dose-response relationship across short-term and long-term studies was revealed linking pulmonary retained surface area dose (measured or estimated) and % PMN. This relationship takes the form of sigmoid curves, and is independent of the post-exposure time. Curve fitting equations depended on the class of NM considered, and sometimes on the duration of exposure. Based on retained surface area, long and thick MWCNTs (few hundred nm long with an aspect ratio greater than 25) had a higher inflammatory potency with 5 cm2/g lung sufficient to trigger an inflammatory response (at 6% PMN), whereas retained surfaces greater than 150 cm2/g lung were required for PSLT. Retained surface area is a useful metric for hazard grouping purposes. This metric would apply to both micrometric and nanometric materials, and could obviate the need for direct measurement in the lung. Indeed, it could alternatively be estimated from dosimetry models using the aerosol parameters (rigorously determined following a well-defined aerosol characterization strategy).

中文翻译:

在急性、亚急性和亚慢性吸入纳米材料后,保留的颗粒表面积剂量会导致大鼠肺部炎症

纳米材料 (NM) 风险评估的一个重要方面是建立理化特性与控制导致不良结果的毒理学途径的关键事件之间的关系。如果使用最毒理学相关的剂量指标来评估毒理学剂量反应,则可以简化 NM 分组的难度。在这里,我们彻底研究了急性和慢性炎症(基于肺支气管肺泡灌洗液中的多形核中性粒细胞流入 (% PMN))与肺中保留的表面积之间的关系。在大鼠中进行了三类 NMs 的吸入研究:二氧化钛 (TiO2) 和炭黑 (CB) 作为难溶性低毒性颗粒 (PSLT),以及多壁碳纳米管 (MWCNT)。我们将我们的结果与近 30 篇经过严格挑选的文章的已发表数据进行了比较。该分析结合了在亚急性(4 周)吸入后针对三种基准材料(TiO2 P25、CB Printex-90 和 MWCNT MWNT-7)专门为这项工作生成的数据以及与急性(1 周)到亚慢性吸入相关的已发表数据(13 周)吸入暴露于所考虑的 NMs 类别。短期和长期暴露后恢复时间(暴露后立即恢复长达 6 个月以上)使我们能够检查急性和慢性炎症。跨短期和长期研究的剂量-反应关系揭示了肺保留表面积剂量(测量或估计)和 PMN 百分比之间的联系。这种关系采用 sigmoid 曲线的形式,与曝光后时间无关。曲线拟合方程取决于所考虑的 NM 类别,有时还取决于暴露时间。基于保留的表面积,长而厚的 MWCNT(几百纳米长,纵横比大于 25)具有更高的炎症效力,5 cm2/g 肺足以触发炎症反应(6% PMN),而保留的表面PSLT 需要大于 150 cm2/g 肺。保留表面积是用于危险分组的有用指标。该指标适用于微米和纳米材料,并且可以避免在肺部直接测量的需要。事实上,它也可以使用气溶胶参数(根据明确定义的气溶胶表征策略严格确定)从剂量学模型中估计。基于保留的表面积,长而厚的 MWCNT(几百纳米长,纵横比大于 25)具有更高的炎症效力,5 cm2/g 肺足以引发炎症反应(6% PMN),而保留的表面PSLT 需要大于 150 cm2/g 肺。保留表面积是用于危险分组的有用指标。该指标适用于微米和纳米材料,并且可以避免在肺部直接测量的需要。事实上,它也可以使用气溶胶参数(根据明确定义的气溶胶表征策略严格确定)从剂量学模型中估计。基于保留的表面积,长而厚的 MWCNT(几百纳米长,纵横比大于 25)具有更高的炎症效力,5 cm2/g 肺足以触发炎症反应(6% PMN),而保留的表面PSLT 需要大于 150 cm2/g 肺。保留表面积是用于危险分组的有用指标。该指标适用于微米和纳米材料,并且可以避免在肺部直接测量的需要。事实上,它也可以使用气溶胶参数(根据明确定义的气溶胶表征策略严格确定)从剂量学模型中估计。长而厚的 MWCNT(几百纳米长,纵横比大于 25)具有更高的炎症效力,5 cm2/g 肺足以引发炎症反应(6% PMN),而保留表面大于 150 cm2/g PSLT 需要肺。保留表面积是用于危险分组的有用指标。该指标适用于微米和纳米材料,并且可以避免在肺部直接测量的需要。事实上,它也可以使用气溶胶参数(根据明确定义的气溶胶表征策略严格确定)从剂量学模型中估计。长而厚的 MWCNT(几百纳米长,纵横比大于 25)具有更高的炎症效力,5 cm2/g 肺足以引发炎症反应(6% PMN),而保留表面大于 150 cm2/g PSLT 需要肺。保留表面积是用于危险分组的有用指标。该指标适用于微米和纳米材料,并且可以避免在肺部直接测量的需要。事实上,它也可以使用气溶胶参数(根据明确定义的气溶胶表征策略严格确定)从剂量学模型中估计。该指标适用于微米和纳米材料,并且可以避免在肺部直接测量的需要。事实上,它也可以使用气溶胶参数(根据明确定义的气溶胶表征策略严格确定)从剂量学模型中估计。该指标适用于微米和纳米材料,并且可以避免在肺部直接测量的需要。事实上,它也可以使用气溶胶参数(根据明确定义的气溶胶表征策略严格确定)从剂量学模型中估计。
更新日期:2021-08-05
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