The toxicological effect of 4-week repeated intravenous injection of activin a/BMP-2 chimera and 2-week recovery study in Beagle dog*

Shi Huan Han, Guang Bin Zheng, Jae Hyup Lee

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1 Citation (Scopus)

Abstract

The purposes of this study was to determine the toxicological effect of repeated intravenous administration of Activin A/BMP-2 chimera (AB204) in beagle dogs for a long period of four weeks and evaluate two-week recovery. AB204 was administered at doses of 0.08, 0.16, or 0.32 mg/kg/day to three male and three female beagle dogs for 4 weeks as the experimental group. For the control group, sterile saline was administered to three male and three female beagle dogs. For the two-week recovery test, two male and two female beagle dogs were randomly selected from the control group and the 0.32 mg/kg/day administered experimental group. General symptoms, body weight, food consumption, ophthalmological examination, electrocardiogram, urinalysis, hematology and blood biochemistry, organ weights, autopsy, and histopathological examination were observed or conducted. No animals died. There was no significant difference in any parameter evaluated between the experimental group and the control group. Histopathological examination revealed compound inflammation at the administration site in both the experimental group and the control group. The inflammation disappeared during the two-week recovery. These results indicated that repetitive intravenous injection of AB204 in beagle dog for a long period of four weeks did not show any toxicity. Therefore, no observed adverse effects level (NOAEL) of AB204 was 0.32 mg/kg/day in big animal model.

Original languageEnglish
JournalDrug and Chemical Toxicology
DOIs
StatePublished - 1 Jan 2019

Fingerprint

Activins
Intravenous Injections
Toxicology
Dogs
Recovery
Control Groups
Animals
Biochemistry
Inflammation
No-Observed-Adverse-Effect Level
Electrocardiography
Urinalysis
Organ Size
Toxicity
Hematology
Blood
Intravenous Administration
Autopsy
Animal Models
Body Weight

Keywords

  • AB204
  • beagle dog
  • intravenous administration
  • recovery test
  • repetitive administration
  • toxicity

Cite this

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title = "The toxicological effect of 4-week repeated intravenous injection of activin a/BMP-2 chimera and 2-week recovery study in Beagle dog*",
abstract = "The purposes of this study was to determine the toxicological effect of repeated intravenous administration of Activin A/BMP-2 chimera (AB204) in beagle dogs for a long period of four weeks and evaluate two-week recovery. AB204 was administered at doses of 0.08, 0.16, or 0.32 mg/kg/day to three male and three female beagle dogs for 4 weeks as the experimental group. For the control group, sterile saline was administered to three male and three female beagle dogs. For the two-week recovery test, two male and two female beagle dogs were randomly selected from the control group and the 0.32 mg/kg/day administered experimental group. General symptoms, body weight, food consumption, ophthalmological examination, electrocardiogram, urinalysis, hematology and blood biochemistry, organ weights, autopsy, and histopathological examination were observed or conducted. No animals died. There was no significant difference in any parameter evaluated between the experimental group and the control group. Histopathological examination revealed compound inflammation at the administration site in both the experimental group and the control group. The inflammation disappeared during the two-week recovery. These results indicated that repetitive intravenous injection of AB204 in beagle dog for a long period of four weeks did not show any toxicity. Therefore, no observed adverse effects level (NOAEL) of AB204 was 0.32 mg/kg/day in big animal model.",
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