title: Spontaneous and Dosing Route-related Lung Lesions in Beagle Dogs from Oral Gavage and Inhalation Toxicity Studies: Differentiation from Compound-induced Lesions.
abstract: This study was conducted to characterize lung microscopic lesions in control beagle dogs from inhalation and oral gavage toxicity studies, to determine differences associated with the route of administration, and to discuss distinguishing features from compound-induced lung lesions. Samples from 138 control dogs from oral gavage studies and 124 control dogs from inhalation (vehicle control) studies were evaluated microscopically. There was no significant sex-related difference in the incidence of all lesions. Perivascular mononuclear cell infiltration, centriacinar mixed cell infiltration, bronchopneumonia, subpleural septal fibrosis, and alveolar macrophage accumulation were the most common lesions. Aspiration pneumonia was more common in dogs from gavage studies, suggesting reflux after gavage dosing or accidental administration of test formulation as possible causes. Centriacinar mixed cell infiltration was more common in dogs from inhalation studies, suggesting mild irritation by the vehicles used. Vascular lesions, which included pulmonary arteriopathy and smooth muscle mineralization, were observed in a few animals. Some of the spontaneous lesions are similar to lesions induced by test compounds. Compared to spontaneous lesions, compound-induced lesions tend to be multifocal or diffuse, follow a pattern of distribution (e.g., centriacinar, perivascular, and interstitial), show a dose response in the incidence and severity, and may show cell-specific toxicity.
authors.affiliation: Charles River Laboratories Edinburgh Ltd., Elphinstone Research Centre, Tranent, United Kingdom begonya.garcia@crl.com.
authors.forename: Sydney
authors.initials: S
authors.lastname: Mukaratirwa
authors.affiliation: Charles River Laboratories Edinburgh Ltd., Elphinstone Research Centre, Tranent, United Kingdom.
authors.forename: Begonya
authors.initials: B
authors.lastname: Garcia
authors.affiliation: Charles River Laboratories Edinburgh Ltd., Elphinstone Research Centre, Tranent, United Kingdom.
authors.forename: Kaori
authors.initials: K
authors.lastname: Isobe
authors.affiliation: Charles River Laboratories Edinburgh Ltd., Elphinstone Research Centre, Tranent, United Kingdom.
authors.forename: Claudio
authors.initials: C
authors.lastname: Petterino
authors.affiliation: Charles River Laboratories Edinburgh Ltd., Elphinstone Research Centre, Tranent, United Kingdom.
authors.forename: Alys
authors.initials: A
authors.lastname: Bradley
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D004285:Dogs; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D018675:Toxicity Tests / Q000379:methods*
keywords: beagle dog; gavage; induced lesions; inhalation; lung; spontaneous lesions