Germann P G, Ockert D, Heinrichs M
Institute of Pathology and Toxicology, Hamburg, Germany.
Toxicol Pathol. 1998 Mar-Apr;26(2):283-9. doi: 10.1177/019262339802600215.
The sagittolongitudinal histopathological evaluation of the oropharyngeal cavity in 6 strains of rats revealed a clear predisposition of the Fischer 344 strain for degenerative and inflammatory lesions in this region. A degeneration and calcification predominantly of the laryngeal cartilage is evident in 72%, granulomas of the seromucinous glands in 38%, and an inflammation with bacterial colonies or plant material in the basal part of the laryngotracheal junction in 26% of the Fischer 344 rats. The incidences of these types of lesions were negligible in the other rat strains evaluated. The comparison of control Fischer 344 rats from 2 carcinogenicity studies (untreated group; gavaged group with water, pH 10; gavaged group with propylene glycol/methocel) showed an influence of the gavage technique with the solvent on the survival rate in the female Fischer 344 rats. The lower survival rate was accompanied by the occurrence of food impaction in the oropharyngeal cavity. This increased mortality in female Fischer 344 rats was also associated with a degeneration of the laryngeal cartilages, whereas the formation of granulomas and inflammation seemed to have no direct relationship to the mortality. The gavage technique with the applied solvent was an enhancing factor in the female Fischer 344 rats on mortality, on cartilage degeneration, but not on inflammatory changes. In contrast to the females, male Fischer 344 rats had a higher incidence of granulomas and inflammation, which, however, did not influence the survival rate. In conclusion, Fischer 344 rats, especially the female sex, exposed to chronic daily irritation by gavage, are predisposed to have a high mortality rate in chronic toxicologic tests. An explanation lies in the disposition of the Fischer 344 rat to a high incidence of cartilage degeneration, which presumably leads to a dysfunction of the larynx.
对6个品系大鼠的口咽腔进行矢状纵向组织病理学评估发现，Fischer 344品系在该区域明显易发生退行性和炎性病变。72%的Fischer 344大鼠出现主要为喉软骨的变性和钙化，38%出现浆液黏液腺肉芽肿，26%在喉气管交界处基部出现伴有细菌菌落或植物性物质的炎症。在评估的其他大鼠品系中，这些类型病变的发生率可忽略不计。对来自2项致癌性研究的对照Fischer 344大鼠（未处理组；用pH 10的水灌胃组；用丙二醇/甲基纤维素灌胃组）进行比较发现，灌胃技术及溶剂对雌性Fischer 344大鼠的存活率有影响。较低的存活率伴随着口咽腔食物嵌塞的发生。雌性Fischer 344大鼠死亡率的增加还与喉软骨变性有关，而肉芽肿的形成和炎症似乎与死亡率没有直接关系。所用溶剂的灌胃技术是雌性Fischer 344大鼠死亡率及软骨变性的增强因素，但对炎症变化无影响。与雌性不同，雄性Fischer 344大鼠肉芽肿和炎症的发生率较高，但这并未影响存活率。总之，在慢性毒理学试验中，经口灌胃受到慢性每日刺激的Fischer 344大鼠，尤其是雌性，易出现高死亡率。原因在于Fischer 344大鼠易发生高发生率的软骨变性，这可能导致喉部功能障碍。
