Lee K P, Kelly D P, O'Neal F O, Stadler J C, Kennedy G L
Central Research & Development Department, E.I. du Pont de Nemours & Company, Haskell Laboratory for Toxicology and Industrial Medicine, Newark, Delaware 19714.
Fundam Appl Toxicol. 1988 Jul;11(1):1-20. doi: 10.1016/0272-0590(88)90265-5.
Four groups of 100 male and 100 female rats were exposed to ultrafine Kevlar fibrils at concentrations of 0, 2.5, 25, and 100 fibrils/cc for 6 hr/day, 5 days/week for 2 years. One group was exposed to 400 fibrils/cc for 1 year and allowed to recover for 1 year. At 2.5 fibrils/cc, the lungs had normal alveolar architecture with a few dust-laden macrophages (dust cell response) in the alveolar airspaces. At 25 fibrils/cc, the lungs showed a dust cell response, slight Type II pneumocyte hyperplasia, alveolar bronchiolarization, and a negligible amount of collagenized fibrosis in the alveolar duct region. At 100 fibrils/cc, the same pulmonary responses were seen as at 25 fibrils/cc. In addition, cystic keratinizing squamous cell carcinoma (CKSCC) was found in 4 female rats, but not in male rats. Female rats had more prominent foamy alveolar macrophages, cholesterol granulomas, and alveolar bronchiolarization. These pulmonary lesions were related to the development of CKSCC. The lung tumors were derived from metaplastic squamous cells in areas of alveolar bronchiolarization. At 400 fibrils/cc following 1 year of recovery, the lung dust content, average fiber length, and the pulmonary lesions were markedly reduced, but slight centriacinar emphysema and minimal collagenized fibrosis were found in the alveolar duct region. One male and 6 female rats developed CKSCC. The lung tumors were a unique type of experimentally induced tumors in the rats and have not been seen as spontaneous tumors in man or animals. Therefore, the relevance of this type of lung tumor to the human situation is minimal.
将四组每组100只雄性和100只雌性大鼠暴露于浓度分别为0、2.5、25和100根/立方厘米的超细凯夫拉尔纤维中，每天暴露6小时，每周暴露5天，持续2年。一组暴露于400根/立方厘米的环境中1年，然后让其恢复1年。在2.5根/立方厘米的浓度下，肺部肺泡结构正常，肺泡气腔内有少量含尘巨噬细胞（尘细胞反应）。在25根/立方厘米的浓度下，肺部出现尘细胞反应、轻度II型肺泡上皮细胞增生、肺泡细支气管化生，肺泡导管区域有少量胶原化纤维化。在100根/立方厘米的浓度下，观察到与25根/立方厘米时相同的肺部反应。此外，在4只雌性大鼠中发现了囊性角化鳞状细胞癌（CKSCC），雄性大鼠中未发现。雌性大鼠有更明显的泡沫状肺泡巨噬细胞、胆固醇肉芽肿和肺泡细支气管化生。这些肺部病变与CKSCC的发生有关。肺肿瘤源自肺泡细支气管化生区域的化生鳞状细胞。在400根/立方厘米的浓度下暴露1年后恢复，肺尘埃含量、平均纤维长度和肺部病变明显减少，但在肺泡导管区域发现了轻度的小叶中心型肺气肿和少量的胶原化纤维化。1只雄性和6只雌性大鼠发生了CKSCC。这种肺肿瘤是大鼠中一种独特的实验诱导肿瘤，在人类或动物中尚未见自发肿瘤。因此，这种类型的肺肿瘤与人类情况的相关性极小。
