Effects of four-week feed restriction on toxicological parameters in beagle dogs

This study was conducted to examine any changes caused by feed restriction in dogs tocontribute to safety evaluation in toxicity studies. Two male 7-month-old beagledogs/group were fed 300 (control), 150 (50% of control), or 70 g/animal of diet daily (23%of control) for 4 weeks. Effects of feed restriction, except for clinical signs, werenoted depending on the feed dosage in almost all examinations. The principal outcomeswere: decreased body weight and water consumption, ECG changes (decreased heart rate andprolonged QTc), and hematopoietic and lymphopoietic suppression (decreased reticulocyteratio or white blood cell count in hematology, decreased nucleated cell count in bonemarrow, decreased erythroid parameters in myelography, and hypocellularity of bone marrowand thymic atrophy in histopathology). In addition, some changes were noted in urinalysis(decreased urine volume and sodium and potassium excretion), blood chemistry (decreasedALP and inorganic phosphorus and increased creatinine), organ weights, and gastrichistopathology. These results provide important reference data for distinguishing theprimary effects of test compounds from secondary effects of decreased food consumption intoxicity studies in beagle dogs.