Novel Techniques for Testing of Esophageal Irritancy of Liquids and Tablets in Dogs.
Esophageal irritation is a potential side effect of oral medications in humans. However, this complication is rarely evaluated in animal studies, in which test compounds are usually delivered directly into the stomach via gavage. The toxicology unit at our institution required development of a model to test compounds in liquid and tablet form for esophageal irritancy. To deliver liquids, an endotracheal tube (internal diameter, 5.0 mm) was passed into the esophagus of anesthetized dogs, with the cuff inflated directly caudal to the larynx. A rubber catheter (size, 8 French) was then passed through the tube, extending caudally 1 in past the end of the tube. An infusion pump delivered the test liquid through the catheter over a 30-min period. The cranial portion of the dog was elevated, so that the liquid would flow aborally. The infusions were generally administered for 5 consecutive days, and the dogs euthanized on the fifth day for gross and histopathologic examination of the esophagus. This technique was performed successfully on 80 dogs, without serious complication. For delivery of compounds in tablet form, a clear tube was passed into the cranial third of the esophagus. The tablet, tied to a pre-measured length of silk suture, was then introduced into the esophagus through the tube by using endoscopic retrieval forceps. The tablets were left in place for 1 h, and the dogs were then euthanized and examined. These techniques allowed for accurate and reliable testing in dogs of the esophageal irritancy of compounds in either the liquid or tablet form.
Smith
Susanne
S
Laboratory Animal Resources1 and Safety Assessment,2 Merck Research Laboratories, Sumneytown Pike, West Point, PA 19486.
Handt
Laurence
L
Peter
Chennekatu
C
Klein
Hilton
H