Effects of reduced food intake on the parameters of toxicity evaluation in dogs

It is crucial to evaluate the variations in the toxicity parameters in experimental animals during the development of new drugs. Reduced food intake has been reported to have an impact on the toxicity parameters in rats; however, there are few reports of such studies in dogs. The aim of this study was to clarify the effects of reduced food intake on the general toxicity parameters and their reversibility in dogs. Male beagle dogs were fed 300 g/day of diet for 12 weeks in the control group, and 150 g/day for the first 8 weeks and 200 g/day for the subsequent 4 weeks in the low feeding group. During the following 4-week recovery period, the amount of feeding was set at 300 g/day. There were no clinical changes in any of the dogs. The low feeding group showed a body weight loss of 9.0%, 16.7% and 14.3% relative to the pre-test values at Week 4, 8 and 12, respectively. The following changes from the pre-test values and/or the control group in the examined parameters were observed in this group: decreased heart rate, prolonged PR interval on the ECG, decreased leukocyte count, and increased serum free fatty acid and γ-glutamyl transpeptidase levels. Significant changes of these parameters were not observed any more during the recovery period. This fact supports biological or physiological reaction to reduced food intake. These results are considered to represent useful information for toxicologists to distinguish between the direct effects of drugs and the changes attributable to reduced food intake.