Warheit D B, Carakostas M C, Kelly D P, Hartsky M A
Haskell Laboratory for Toxicology and Industrial Medicine, E.I. du Pont de Nemours and Company, Newark, Delaware 19714.
Fundam Appl Toxicol. 1991 Apr;16(3):590-601. doi: 10.1016/0272-0590(91)90098-o.
This study was designed to complement a traditional subchronic inhalation toxicity study with Ludox colloidal silica. CD rats were exposed nose-only for 2 or 4 weeks at concentrations of 0, 10, 50, and 150 mg/m3 Ludox (dried SiO2). Additional groups of rats exposed for 4 weeks were given a 3-month recovery period. Following exposure and/or recovery, fluids and cells were recovered from the lungs by bronchoalveolar lavage (BAL) and measured for cellular and biochemical parameters. Additional groups of animals were processed for cell labeling studies or lung deposition studies. Inhaled doses of Ludox colloidal silica were measured after 4-week exposures and were found to be 489 micrograms/lung (10 mg/m3 group), 2418 micrograms/lung (50 mg/m3), and 7378 micrograms/lung (150 mg/m3), respectively. Results showed that exposures to 150 mg/m3 Ludox for 2 or 4 weeks produced pulmonary inflammation along with increases in BAL protein, LDH, and alkaline phosphatase values (p less than 0.05) and reduced macrophage phagocytosis. Inflammatory responses, evidenced by increased numbers of neutrophils, were also measured in the lungs of the 50 mg/m3 group following 2 and/or 4 weeks of exposure. Most biochemical parameters for all groups returned to control values following a 3-month recovery period. Autoradiographic studies demonstrated that the labeling indices of terminal bronchiolar and lung parenchymal cells were generally increased in the 50 and 150 mg/m3 groups after 2 and 4 weeks of exposure but, with one exception, returned to normal levels following a 3-month postexposure period. No significant alterations in any measured parameters were detected in rats exposed to 10 mg/m3 Ludox at any time postexposure. The determination of a no-observable-effect level (NOEL) of 10 mg/m3 was consistent with results obtained by conventional toxicology methods and affirms the utility of these biochemical, cellular, and autoradiographic techniques for providing a predictive screen to assess the toxicity of inhaled particles.
本研究旨在补充一项关于Ludox胶体二氧化硅的传统亚慢性吸入毒性研究。将CD大鼠仅经鼻暴露于浓度为0、10、50和150 mg/m³的Ludox（干燥的SiO₂）环境中2或4周。另外，将暴露4周的大鼠组给予3个月的恢复期。在暴露和/或恢复后，通过支气管肺泡灌洗（BAL）从肺中回收液体和细胞，并测量细胞和生化参数。对另外几组动物进行细胞标记研究或肺沉积研究。在4周暴露后测量吸入的Ludox胶体二氧化硅剂量，发现分别为489微克/肺（10 mg/m³组）、2418微克/肺（50 mg/m³）和7378微克/肺（150 mg/m³）。结果表明，暴露于150 mg/m³的Ludox 2或4周会导致肺部炎症，同时BAL蛋白、乳酸脱氢酶（LDH）和碱性磷酸酶值升高（p小于0.05），巨噬细胞吞噬作用降低。在暴露2周和/或4周后的50 mg/m³组大鼠肺中也检测到以中性粒细胞数量增加为证据的炎症反应。在3个月的恢复期后，所有组的大多数生化参数恢复到对照值。放射自显影研究表明，在暴露2周和4周后，50和150 mg/m³组终末细支气管和肺实质细胞的标记指数通常会增加，但有一个例外，在暴露后3个月恢复到正常水平。在暴露后任何时间，暴露于10 mg/m³ Ludox的大鼠未检测到任何测量参数的显著变化。确定10 mg/m³的无可见效应水平（NOEL）与通过传统毒理学方法获得的结果一致，并证实了这些生化、细胞和放射自显影技术在提供预测性筛选以评估吸入颗粒毒性方面的实用性。
