Single dose toxicity study of CKD-602, a new camptothecin anticancer agent, in Beagle dogs

개에서 새로운 캄토테신계 항암제 CKD-602의 단회투여독성시험

  • 김종춘 (전남대학교 수의과대학) ;
  • 신동호 (전남대학교 수의과대학) ;
  • 박승춘 (경북대학교 수의과대학) ;
  • 손우찬 ;
  • 차신우 (한국화학연구원 부설 안전성평가연구소) ;
  • 한정희 (한국화학연구원 부설 안전성평가연구소) ;
  • 배주현 (한국화학연구원 부설 안전성평가연구소) ;
  • 서정은 (한국화학연구원 부설 안전성평가연구소) ;
  • 정문구 (한국화학연구원 부설 안전성평가연구소)
  • Accepted : 2004.03.04
  • Published : 2004.03.31

Abstract

The present study was carried out to investigate the potential acute toxicity of CKD-602 by a single intravenous dose in Beagle dogs. The test chemical was administered intravenously to male and female Beagle dogs at dose levels of 0.3, 0.5, or 2.5 mg/kg. Mortalities, clinical findings, and body weight changes were monitored for the 14-day period following the administration. At the end of 14-day observation period, all animals were sacrificed and complete gross postmortem examinations were performed. All males and females of the 2.5 mg/kg dose group were found dead between the fourth and seventh day after the injection. Treatment related clinical signs, including vomiting, anorexia, mucous stool, diarrhea, and no stool were observed. Decrease or suppression of body weight was observed in a dose-dependent manner. In autopsy, dark red discoloration of the gastrointestinal tract, atrophy of the thymus, paleness of the spleen, sporadic dark red spots of the lung and petechia of the heart were observed in dead animals of the 2.5 mg/kg dose group. There were no specific adverse effects on males and females of the 0.3 and 0.5 mg/kg dose groups, except for the transient clinical signs such as anorexia, vomiting, and mucus/no stool. On the basis of the results, it was concluded that a single intravenous injection of CKD-602 to Beagle dogs resulted in increased incidence of abnormal clinical signs and death, decreased body weight, and increased incidence of abnormal gross findings. The absolute toxic dose of this chemical was 2.5 mg/kg for both genders. The $LD_{50}$ value was 1.1 mg/kg (95% confidence limit not specified) for both genders. The no-observed-effect level (NOEL) was considered to be below 0.3 mg/kg for both genders.

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