Henderson R F, Driscoll K E, Harkema J R, Lindenschmidt R C, Chang I Y, Maples K R, Barr E B
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185, USA.
Fundam Appl Toxicol. 1995 Feb;24(2):183-97. doi: 10.1006/faat.1995.1022.
The potential pulmonary toxicity of poorly soluble airborne dusts generated in industrial and environmental settings is often evaluated by inhalation studies in rodents. Studies using intratracheal instillation of particles have been suggested as a less expensive alternative. We conducted a study to compare the inflammatory response of the lung to instilled versus inhaled particles. In one study, female F344/N rats, 11-13 weeks of age, were exposed for 6 hr/day, 5 days/week for 4 weeks by inhalation to 0, 0.1, 1.0, or 10 mg/m3 of either alpha-quartz (toxic particle) or TiO2 (relatively low toxicity particle) and the lung burdens were determined at 1 week after the end of the exposure. The lungs were evaluated by analysis of bronchoalveolar lavage fluid (BALF) at 1, 8, and 24 weeks after the end of the exposure and by histopathology at 24 weeks. In a second study, rats were exposed by instillation to the lung burdens present in the preceding study at 1 week after the inhalation exposure, and the rats were evaluated in the same manner as in the inhalation study. In general, the degree of alveolitis, as evaluated by histopathology and BALF analysis, was similar by the two methods of exposure. With lung burdens up to 750 micrograms/g lung, the TiO2 elicited no changes in BALF parameters at any time by either method of exposure, nor was any histopathology observed. The BALF changes elicited by alpha-quartz were of approximately the same magnitude and followed the same time course by either exposure method with the lowest dose delivered to the lung by either method being a "no-effect" dose. At the highest dose, microgranulomas were observed in bronchial-associated lymphoid tissue (BALT) in both sets of rats. However, the highest inhalation exposure induced pleural granulomatous lesions that were not observed in the animals instilled with alpha-quartz. The results indicate that the relative potentials of the two materials to produce bronchoalveolitis and granulomatous lesions in BALT could be appropriately evaluated using either intratracheal or inhalation exposures.
工业和环境中产生的难溶性空气传播粉尘的潜在肺毒性通常通过对啮齿动物进行吸入研究来评估。有人建议使用气管内滴注颗粒的研究作为一种成本较低的替代方法。我们进行了一项研究，以比较肺部对滴注颗粒与吸入颗粒的炎症反应。在一项研究中，将11 - 13周龄的雌性F344/N大鼠，每天暴露6小时，每周5天，持续4周，通过吸入0、0.1、1.0或10 mg/m³的α-石英（有毒颗粒）或TiO₂（相对低毒颗粒），并在暴露结束后1周测定肺负荷。在暴露结束后1、8和24周通过分析支气管肺泡灌洗液（BALF）以及在24周通过组织病理学对肺部进行评估。在第二项研究中，在吸入暴露后1周，通过滴注使大鼠接触前一项研究中存在的肺负荷，并以与吸入研究相同的方式对大鼠进行评估。一般来说，通过组织病理学和BALF分析评估的肺泡炎程度，两种暴露方法相似。当肺负荷高达750微克/克肺时，无论采用哪种暴露方法，TiO₂在任何时候都不会引起BALF参数的变化，也未观察到任何组织病理学变化。α-石英引起的BALF变化幅度大致相同，并且无论采用哪种暴露方法，时间进程相同，两种方法输送到肺部的最低剂量均为“无效应”剂量。在最高剂量时，两组大鼠的支气管相关淋巴组织（BALT）中均观察到微肉芽肿。然而，最高吸入暴露诱导了胸膜肉芽肿性病变，而在滴注α-石英的动物中未观察到。结果表明，使用气管内滴注或吸入暴露可以适当地评估这两种材料在BALT中产生支气管肺泡炎和肉芽肿性病变的相对潜力。
