Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, United States of America.
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, United States of America.
Toxicol Appl Pharmacol. 2020 Dec 1;408:115280. doi: 10.1016/j.taap.2020.115280. Epub 2020 Oct 13.
The pulmonary inflammatory response to inhalation exposure to a fracking sand dust (FSD 8) was investigated in a rat model. Adult male Sprague-Dawley rats were exposed by whole-body inhalation to air or an aerosol of a FSD, i.e., FSD 8, at concentrations of 10 or 30 mg/m, 6 h/d for 4 d. The control and FSD 8-exposed rats were euthanized at post-exposure time intervals of 1, 7 or 27 d and pulmonary inflammatory, cytotoxic and oxidant responses were determined. Deposition of FSD 8 particles was detected in the lungs of all the FSD 8-exposed rats. Analysis of bronchoalveolar lavage parameters of toxicity, oxidant generation, and inflammation did not reveal any significant persistent pulmonary toxicity in the FSD 8-exposed rats. Similarly, the lung histology of the FSD 8-exposed rats showed only minimal changes in influx of macrophages following the exposure. Determination of global gene expression profiles detected statistically significant differential expressions of only six and five genes in the 10 mg/m, 1-d post-exposure, and the 30 mg/m, 7-d post-exposure FSD 8 groups, respectively. Taken together, data obtained from the present study demonstrated that FSD 8 inhalation exposure resulted in no statistically significant toxicity or gene expression changes in the lungs of the rats. In the absence of any information about its potential toxicity, a comprehensive rat animal model study (see Fedan, J.S., Toxicol Appl Pharmacol. 000, 000-000, 2020) has been designed to investigate the bioactivities of several FSDs in comparison to MIN-U-SIL® 5, a respirable α-quartz reference dust used in previous animal models of silicosis, in several organ systems.
本研究旨在大鼠模型中探究吸入压裂砂尘（FSD 8）后肺部的炎症反应。成年雄性 Sprague-Dawley 大鼠经全身吸入暴露于空气或 FSD 气溶胶（即 FSD 8），浓度分别为 10 或 30mg/m3，6h/d，共 4d。对照组和 FSD 8 暴露组大鼠分别在暴露后 1、7 或 27d 处死，检测肺部炎症、细胞毒性和氧化应激反应。所有 FSD 8 暴露组大鼠的肺部均检测到 FSD 8 颗粒沉积。毒理学、氧化应激生成和炎症的支气管肺泡灌洗参数分析并未显示 FSD 8 暴露组大鼠有明显的持续性肺部毒性。同样，FSD 8 暴露组大鼠的肺组织学检查显示，暴露后仅观察到巨噬细胞浸润有轻微变化。全基因表达谱分析显示，在 10mg/m3、1d 暴露后以及 30mg/m3、7d 暴露后，FSD 8 组大鼠肺部仅有 6 个和 5 个基因的表达有统计学显著差异。综上所述，本研究数据表明，FSD 8 吸入暴露不会导致大鼠肺部出现明显的毒性或基因表达变化。由于缺乏其潜在毒性的相关信息，我们设计了一项全面的大鼠动物模型研究（见 Fedan, J.S., Toxicol Appl Pharmacol. 000, 000-000, 2020），以比较几种 FSD 与 MIN-U-SIL® 5（一种先前用于矽肺动物模型的可吸入性α-石英参考粉尘）在多个器官系统中的生物活性。
