title: Effects of four-week feed restriction on toxicological parameters in beagle dogs.
abstract: This study was conducted to examine any changes caused by feed restriction in dogs to contribute to safety evaluation in toxicity studies. Two male 7-month-old beagle dogs/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, were noted depending on the feed dosage in almost all examinations. The principal outcomes were: decreased body weight and water consumption, ECG changes (decreased heart rate and prolonged QTc), and hematopoietic and lymphopoietic suppression (decreased reticulocyte ratio or white blood cell count in hematology, decreased nucleated cell count in bone marrow, decreased erythroid parameters in myelography, and hypocellularity of bone marrow and thymic atrophy in histopathology). In addition, some changes were noted in urinalysis (decreased urine volume and sodium and potassium excretion), blood chemistry (decreased ALP and inorganic phosphorus and increased creatinine), organ weights, and gastric histopathology. These results provide important reference data for distinguishing the primary effects of test compounds from secondary effects of decreased food consumption in toxicity studies in beagle dogs.
authors.affiliation: Drug Safety Research Laboratories, Astellas Pharma Inc., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takamatsu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamashita
authors.forename: Shigeru
authors.initials: S
authors.lastname: Satake
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kazusa
authors.forename: Hajime
authors.initials: H
authors.lastname: Tabata
authors.forename: Takahito
authors.initials: T
authors.lastname: Nishikata
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000821:Animal Feed; D000818:Animals; D001772:Blood Cell Count; D001835:Body Weight / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology; D031204:Caloric Restriction; D003404:Creatinine / Q000097:blood; D004285:Dogs; D004326:Drinking / Q000502:physiology; D004435:Eating / Q000502:physiology*; D004562:Electrocardiography; D005508:Food Deprivation / Q000502:physiology*; D006801:Humans; D008297:Male; D009929:Organ Size; D010710:Phosphates / Q000097:blood; D011188:Potassium / Q000652:urine; D012964:Sodium / Q000652:urine; D013270:Stomach; D013997:Time Factors; D018675:Toxicity Tests
chemical_list: D010710:Phosphates; D012964:Sodium; D003404:Creatinine; D000469:Alkaline Phosphatase; D011188:Potassium
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