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

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  • TAKAMATSU Kazuhiko
    Drug Safety Research Laboratories, Astellas Pharma Inc., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan Department of Nanobioscience, Frontiers of Innovative Research in Science and Technology, Konan University, 7-1-20 Minatojimaminamimachi, Chuo-ku, Kobe 650-0047, Japan
  • YAMASHITA Hiroyuki
    Drug Safety Research Laboratories, Shin Nippon Biomedical Laboratories, Ltd., 2438 Miyanoura, Kagoshima 891-1394, Japan
  • SATAKE Shigeru
    Drug Safety Research Laboratories, Shin Nippon Biomedical Laboratories, Ltd., 2438 Miyanoura, Kagoshima 891-1394, Japan
  • KAZUSA Katsuyuki
    Drug Safety Research Laboratories, Astellas Pharma Inc., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan
  • TABATA Hajime
    Drug Safety Research Laboratories, Astellas Pharma Inc., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan
  • NISHIKATA Takahito
    Department of Nanobioscience, Frontiers of Innovative Research in Science and Technology, Konan University, 7-1-20 Minatojimaminamimachi, Chuo-ku, Kobe 650-0047, Japan

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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.

収録刊行物

  • Experimental Animals

    Experimental Animals 64 (3), 269-280, 2015

    公益社団法人 日本実験動物学会

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