| Single dose toxicity study of CKD-602, a new camptothecin anticancer agent, in Beagle dogs |
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Jong-Choon Kim1, Dong-Ho Shin1, Seung-Chun Park2, Woo-Chan Son3, Shin-Woo Cha4, Junghee Han4, Joo-Hyun Bae4, Jeong-Eun Suh4, Moon-Koo Chung4 |
1College of Veterinary Medicine, Chonnam National University
2College of Veterinary Medicine, Kyungpook National University
3Huntingdon Life Sciences
4Korea Institute of Toxicology, KRICT |
| 개에서 새로운 캄토테신계 항암제 CKD-602의 단회투여독성시험 |
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김종춘1, 신동호1, 박승춘2, 손우찬3, 차신우4, 한정희4, 배주현4, 서정은4, 정문구4 |
1전남대학교 수의과대학
2경북대학교 수의과대학
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4한국화학연구원 부설 안전성평가연구소 |
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| Abstract |
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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. |
| Key Words:
Anticancer agent, CKD-602, camptothecin, acute toxicity, $LD_{50}$ value, dogs |
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