A COMPARISON OF THE INFLAMMATORY RESPONSE OF THE LUNG TO INHALED VERSUS INSTILLED PARTICLES IN F344 RATS
A COMPARISON OF THE INFLAMMATORY RESPONSE OF THE LUNG TO INHALED VERSUS INSTILLED PARTICLES IN F344 RATS
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DOI：
10.1006/faat.1995.1022
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发表时间：
1995-02-01
期刊：
影响因子：
--
通讯作者：
BARR, EB
中科院分区：
文献类型：
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作者：
HENDERSON, RF;DRISCOLL, KE;BARR, EB
工业和环境环境中产生的难溶性气载粉尘的潜在肺毒性通常通过啮齿动物吸入研究来评估。使用微囊内滴注颗粒的研究已被建议作为一种较便宜的替代方案。我们进行了一项研究，以比较肺部对滴注与吸入颗粒的炎症反应。在一项研究中，11-13周龄的雌性F344/N大鼠通过吸入0、0.1、1.0或10 mg/m3的α-石英（有毒颗粒）或TiO 2（毒性相对较低的颗粒），暴露于6小时/天，5天/周，持续4周，并在暴露结束后1周测定肺负荷。通过分析暴露结束后1、8和24周的支气管肺泡灌洗液（BALF）和24周的组织病理学对肺进行评价。在第二项研究中，在吸入暴露后1周，通过滴注将大鼠暴露于先前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价。一般而言，通过组织病理学和BALF分析评价的肺泡炎程度在两种暴露方法中相似。在肺负荷高达750 μ g/g肺的情况下，通过任一暴露方法，TiO 2在任何时间均未引起BALF参数变化，也未观察到任何组织病理学。由α-石英引起的BALF变化具有大致相同的幅度，并且通过任一种暴露方法遵循相同的时间过程，其中通过任一种方法递送到肺部的最低剂量是“无效”剂量。在最高剂量下，在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，最高吸入暴露诱导胸膜肉芽肿性病变，在滴注α-石英的动物中未观察到。结果表明，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可通过气管内或吸入暴露进行适当评价。(C)1995年毒理学学会。
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/m(3) of either alpha-quartz (toxic particle) or TiO2 (relatively low toxicity particle) and the lung burdens were determined at I 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 mu g/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. (C) 1995 Society of Toxicology.