Germann P G, Ockert D, Tuch K
Institute of Pathology and Toxicology, Byk Gulden, Hamburg, Germany.
Toxicol Pathol. 1995 May-Jun;23(3):349-55. doi: 10.1177/019262339502300311.
The development of tracheal cartilage degeneration and inflammation of the seromucinous glands of the oropharynx may be a factor causing early mortalities in long-term studies with Fischer-344 (F-344) rats. The presence of these lesions was investigated in groups of male and female F-344 rats killed at 6, 19, and 32 wk of age. Half of the rats killed at 19 and 32 wk of age were sham treated with water (pH 10) by daily oral gavage for a duration of 13 or 26 wk prior to autopsy in order to detect any influence on the laryngotracheal cavity due to dosing technique. A clear age-associated increase in severity and incidence of chondroid degeneration of the tracheal and laryngeal cartilage was revealed, with an onset as early as 6 wk of age. After 19 wk, a high frequency of oropharyngeal granuloma formation was found. No relationship of the lesions to the gavage technique was apparent. The F-344 rat strain may possess a predisposition for inflammatory and degenerative changes in the oropharyngeal and laryngotracheal cavity, changes that can lead to increased and unexpected mortality rates in nonclinical safety studies (7).
在对Fischer-344（F-344）大鼠进行的长期研究中，气管软骨退变以及口咽浆液性腺炎症的发展可能是导致早期死亡的一个因素。在6周龄、19周龄和32周龄处死的雄性和雌性F-344大鼠组中，对这些病变的存在情况进行了调查。在19周龄和32周龄处死的大鼠中，有一半在尸检前13周或26周通过每日口服灌胃用水（pH 10）进行假处理，以检测给药技术对喉气管腔的任何影响。结果显示，气管和喉软骨的类软骨退变严重程度和发生率明显随年龄增加，最早在6周龄时就已出现。19周后，发现口咽肉芽肿形成的频率很高。病变与灌胃技术之间没有明显关联。F-344大鼠品系可能对口咽和喉气管腔的炎症及退行性变化具有易感性，这些变化可导致非临床安全性研究中的死亡率增加且出人意料（7）。
