Lee K P, Ulrich C E, Geil R G, Trochimowicz H J
Central Research & Development Department, E.I. du Pont de Nemours & Company, Haskell Laboratory for Toxicology & Industrial Medicine, Newark, Delaware 19714.
Fundam Appl Toxicol. 1988 Jan;10(1):125-45. doi: 10.1016/0272-0590(88)90258-8.
Rats were exposed by inhalation to chromium dioxide (CrO2) dust at design concentrations of 0, 0.5 mg/m3 (stabilized and unstabilized, respectively), or 25 mg/m3 (stabilized) for 6 hr/day, 5 days/week for 2 years. No dust-exposure-related pathological changes other than lung lesions were observed in all exposed rats. There were no significant differences in pulmonary responses between unstabilized and stabilized CrO2 at the 0.5 mg/m3 exposure level. The lungs showed minute dust deposition in the alveoli adjacent to the alveolar ducts, but maintained an intact general architecture. The pulmonary responses satisfied the biological criteria for a nuisance dust. At 25 mg/m3, dust deposition was sharply confined to the alveoli in the alveolar duct region. Alveolar walls enclosing dust-laden macrophage (dust cell) aggregates were thickened with hyperplastic Type II pneumocytes and slightly collagenized fibrosis. Alveoli adjacent to the terminal bronchioles were lined with bronchiolar epithelium (alveolar bronchiolarization). In addition, lungs showed foamy macrophage response, cholesterol granulomas, alveolar proteinosis, and minute fibrotic pleurisy. These pulmonary lesions occurred predominantly in female rats. Of 108 female rats, 6 developed keratin cysts and 2 had cystic keratinizing squamous cell carcinoma (CKSCC). None of 106 male rats had either a keratin cyst or a CKSCC. The lung tumors developed from metaplastic squamous cells in the areas of alveolar bronchiolarization at the alveolar duct region. The lung tumors were well differentiated and devoid of characteristics of true malignancy. The CKSCC is an experimentally induced, unique tumor type and is different from the type of spontaneous lung tumor seen in man or animals. The relevance to man of this type of lung tumor appears to be negligible.
将大鼠暴露于设计浓度分别为0、0.5毫克/立方米（分别为稳定态和非稳定态）或25毫克/立方米（稳定态）的二氧化铬（CrO₂）粉尘中，每天6小时，每周5天，持续2年。在所有暴露的大鼠中，除肺部病变外，未观察到与粉尘暴露相关的其他病理变化。在0.5毫克/立方米的暴露水平下，非稳定态和稳定态的CrO₂之间的肺部反应没有显著差异。肺部在肺泡管相邻的肺泡中显示出微小的粉尘沉积，但总体结构保持完整。肺部反应符合 nuisance dust的生物学标准。在25毫克/立方米时，粉尘沉积急剧局限于肺泡管区域的肺泡中。包裹着充满粉尘的巨噬细胞（尘细胞）聚集体的肺泡壁因II型肺细胞增生而增厚，并伴有轻度胶原化纤维化。终末细支气管相邻的肺泡内衬有细支气管上皮（肺泡细支气管化生）。此外，肺部还表现出泡沫状巨噬细胞反应、胆固醇肉芽肿、肺泡蛋白沉积症和微小的纤维性胸膜炎。这些肺部病变主要发生在雌性大鼠中。在108只雌性大鼠中，6只出现角质囊肿，2只患有囊性角化鳞状细胞癌（CKSCC）。106只雄性大鼠中没有一只出现角质囊肿或CKSCC。肺肿瘤由肺泡管区域肺泡细支气管化生区域的化生鳞状细胞发展而来。肺肿瘤分化良好，没有真正恶性肿瘤的特征。CKSCC是一种实验诱导的独特肿瘤类型，与人类或动物中所见的自发性肺肿瘤类型不同。这种类型的肺肿瘤与人类的相关性似乎可以忽略不计。
