Improved oral dosing technique for rats.

Abstract

In a department assessing the safety of potential medicines, it was found that gavage-related death in rats could be virtually eliminated by the use of a modified dosing cannula. It had previously been found with a series of potential therapeutic agents that a number of rodents died with dyspnea following administration by gavage. It was known that this was not due to technical error; gavage with water in control groups led to death with similar symptoms in only one case per 220 rat years, or one in 80,520 doses. Accidental aspiration of small volumes of the oral dose was considered to be responsible for the drug-related deaths. Hypertonic, acidic sodium chloride solutions, used as a control, tonicity- and pH-matched to a compound solution in a long-term study, had similar effects. It was shown in a small experiment that the intratracheal lethal dose was approximately 1/200 the published oral LD50 of NaCl. Cannulae of various diameters, lengths, and materials were tested in order to devise a safer dosing method, which would not cause trauma but would allow economical dosing speeds to be achieved. For adult rats, a steel cannula 70-mm-long, with a maximum tip diameter of 4 mm, was chosen. Lighter rats could be dosed using cannulae of smaller tip diameter according to body weight. The adoption of our method, developed using a few rats, could save many unnecessary deaths in laboratory rodents as well as many spurious "treatment-related" pulmonary symptoms.