title: Granulomatous inflammation of the oropharyngeal cavity as a possible cause for unexpected high mortality in a Fischer 344 rat carcinogenicity study.
abstract: 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.
authors.affiliation: Institute of Pathology and Toxicology, Byk Gulden, Hamburg, Germany.
authors.forename: P G
authors.initials: PG
authors.lastname: Germann
authors.forename: D
authors.initials: D
authors.lastname: Ockert
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests; D005260:Female; D006099:Granuloma / Q000401:mortality / Q000473:pathology / Q000662:veterinary*; D009960:Oropharynx / Q000473:pathology; D010612:Pharyngitis / Q000401:mortality / Q000473:pathology / Q000662:veterinary*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012376:Rodent Diseases / Q000401:mortality* / Q000473:pathology