Warheit D B, Kellar K A, Hartsky M A
Haskell Laboratory for Toxicology and Industrial Medicine, E. I. du Pont de Nemours and Co., Newark, Delaware 19714.
Toxicol Appl Pharmacol. 1992 Oct;116(2):225-39. doi: 10.1016/0041-008x(92)90302-9.
Previous chronic inhalation studies have shown that high concentrations of Kevlar fibrils produced fibrosis and cystic keratinizing tumors in rats following 2-year inhalation exposures. The current studies were undertaken to evaluate mechanisms and to assess the toxicity of inhaled Kevlar fibrils relative to other reference materials. Rats were exposed to ultrafine Kevlar fibers (fibrils) for 3 or 5 days at concentrations ranging from 600-1300 fibers/cc (gravimetric concentrations ranging from 2-13 mg/m3). A complete characterization of the fiber aerosol and dose was carried out. These measurements included gravimetric concentrations, mass median aerodynamic diameter, fiber number, and count median lengths and diameters of the aerosol. Following exposures, cells and fluids from groups of sham- and fiber-exposed animals were recovered by bronchoalveolar lavage (BAL). Alkaline phosphatase, lactate dehydrogenase (LDH), protein, and N-acetyl glucosaminidase (NAG) values were measured in BAL fluids at several time points postexposure. Alveolar macrophages were cultured and studied for morphology, chemotaxis, and phagocytosis by scanning electron microscopy. The lungs of additional exposed animals were processed for deposition, cell labeling, retained dose, and lung clearance studies, as well as fiber dimensions (from digested lung tissue), histopathology, and transmission electron microscopy. Five-day exposures to Kevlar fibrils elicited a transient granulocytic inflammatory response with concomitant increases in BAL fluid levels of alkaline phosphatase, NAG, LDH, and protein. Unlike the data from silica and asbestos exposures where inflammation persisted, biochemical parameters returned to control levels at time intervals between 1 week and 1 month postexposure. Macrophage function in Kevlar-exposed alveolar macrophages was not significantly different from sham controls at any time period. Cell labeling studies were carried out immediately after exposure, as well as 1 week and 1 month postexposure. Increased pulmonary cell labeling was measured in terminal bronchiolar cells immediately after exposure but returned to control values 1 week later. Fiber clearance studies demonstrated a transient increase in the numbers of retained fibers at 1 week postexposure, with rapid clearance of fibers thereafter. The transient increase in the number of fibers could be due to transverse cleaving of the fibers, since the average lengths of retained fibers continued to decrease over time. In this regard, a progressive decrease in the mean lengths and diameters of inhaled fibers was measured over a 6-month postexposure period.(ABSTRACT TRUNCATED AT 400 WORDS)
以往的慢性吸入研究表明，大鼠在2年吸入暴露后，高浓度的凯夫拉尔纤维原纤维会导致纤维化和囊性角化肿瘤。目前的研究旨在评估其作用机制，并评估吸入凯夫拉尔纤维原纤维相对于其他参考材料的毒性。将大鼠暴露于超细凯夫拉尔纤维（原纤维）中3或5天，浓度范围为600 - 1300根/立方厘米（重量浓度范围为2 - 13毫克/立方米）。对纤维气溶胶和剂量进行了全面表征。这些测量包括重量浓度、质量中值空气动力学直径、纤维数量以及气溶胶的计数中值长度和直径。暴露后，通过支气管肺泡灌洗（BAL）回收假暴露组和纤维暴露组动物的细胞和液体。在暴露后的几个时间点测量BAL液中的碱性磷酸酶、乳酸脱氢酶（LDH）、蛋白质和N - 乙酰葡糖胺酶（NAG）值。培养肺泡巨噬细胞，并通过扫描电子显微镜研究其形态、趋化性和吞噬作用。对另外一些暴露动物的肺进行处理，用于沉积、细胞标记、保留剂量和肺清除研究，以及纤维尺寸（来自消化后的肺组织）、组织病理学和透射电子显微镜检查。暴露于凯夫拉尔纤维原纤维5天会引发短暂的粒细胞炎症反应，同时BAL液中碱性磷酸酶、NAG、LDH和蛋白质水平升高。与二氧化硅和石棉暴露的数据不同，在石棉暴露中炎症持续存在，而在本研究中，生化参数在暴露后1周和1个月之间的时间间隔内恢复到对照水平。在任何时间段，暴露于凯夫拉尔纤维的肺泡巨噬细胞中的巨噬细胞功能与假暴露对照组相比均无显著差异。在暴露后立即以及暴露后1周和1个月进行细胞标记研究。暴露后立即在终末细支气管细胞中测量到肺细胞标记增加，但1周后恢复到对照值。纤维清除研究表明，暴露后1周保留纤维数量短暂增加，此后纤维迅速清除。纤维数量的短暂增加可能是由于纤维的横向断裂，因为保留纤维的平均长度随时间持续下降。在这方面，在暴露后6个月的时间里测量到吸入纤维的平均长度和直径逐渐减小。（摘要截断于400字）
