Germann P G, Ockert D
Institute of Pathology and Toxicology, Byk Gulden, Hamburg, Germany.
Lab Anim Sci. 1994 Aug;44(4):338-43.
An unexpected, high, test-substance-unrelated mortality has been found predominantly in female Fischer 344 rats of a 2-year gavage carcinogenicity study, which is still in the active phase. Most of the dead animals (53%) had an impacted food or bedding bolus in the oropharyngeal cavity. Histologic evaluation of this area revealed a calcified, granulomatous inflammation of the sero-mucinous glands (60%), frequently accompanied by papillary projections (50%) into the lumen. Additionally, decentral islet formation of the tracheal cartilage was evident in all animals examined. We assume that the partial blockage of the oropharyngeal lumina was the cause of death, because other possible factors were ruled out. To detect a possible strain-related predisposition, Fischer 344 and Sprague Dawley rats that had been used for technician gavage training were studied. Granulomas and papillary projections, as well as the decentral islet formation in the tracheal cartilage, however, were found in gavaged Fischer 344 but not Sprague Dawley rats. We consider the high mortality to be related to three factors: a predisposition of the Fischer 344 rat strain, an unphysiological pH of the solvent (pH 10), and chronic irritation due to an inflexible, metallic gavage tube.
在一项仍处于进行阶段的为期两年的灌胃致癌性研究中，意外发现与受试物质无关的高死亡率主要出现在雌性Fischer 344大鼠中。大多数死亡动物（53%）的口咽腔内有食物或垫料团块堵塞。该区域的组织学评估显示，浆液黏液腺出现钙化性肉芽肿性炎症（60%），常伴有向管腔内的乳头状突起（50%）。此外，在所有检查的动物中，气管软骨均可见散在的胰岛形成。我们认为口咽腔管腔的部分堵塞是死亡原因，因为其他可能因素已被排除。为检测可能的品系相关易感性，对用于技术人员灌胃培训的Fischer 344大鼠和Sprague Dawley大鼠进行了研究。然而，在接受灌胃的Fischer 344大鼠中发现了肉芽肿、乳头状突起以及气管软骨中的散在胰岛形成，而在Sprague Dawley大鼠中未发现。我们认为高死亡率与三个因素有关：Fischer 344大鼠品系的易感性、溶剂的非生理pH值（pH 10）以及由坚硬的金属灌胃管引起的慢性刺激。
