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Subacute toxicity evaluation of a new camptothecin anticancer agent CKD-602 administered by intravenous injection to rats.
Regul Toxicol Pharmacol. 2004 Dec; 40(3):356-69.RT

Abstract

The subacute toxicity of a new camptothecin anticancer agent, CKD-602, was investigated after 4-week repeated intravenous administration of the chemical in Sprague-Dawley rats. The test chemical was administered intravenously to rats at dose levels of 0, 0.003, 0.013, or 0.067 mg/kg/day for males and 0, 0.004, 0.018, or 0.089 mg/kg/day for females. At the end of the treatment period, 10 rats/sex/group were sacrificed. The remaining 5 rats/sex in the vehicle control and high dose groups continued the study without treatment for 2 weeks (recovery period). During the test period, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were examined. In both sexes of the high dose group, an increase in the incidence of abnormal clinical signs and paleness of the eyes, a reduction in the body weight gain, food consumption and urine protein, and an increase in the water consumption were observed. Hematological investigations revealed a decrease in the red blood cells, hemoglobin and hematocrit and an increase in the mean corpuscular volume, mean corpuscular hemoglobin, platelets, and reticulocytes in a dose-dependent manner. Serum total cholesterol and total protein values were lower in females than those of controls, but not in males. An increase in the heart and liver weights and a decrease in the thymus weight were also found. Histopathological alterations included an increase in the incidence of atrophy of the sternal marrow, atrophy, fibrosis and mast cell hyperplasia of the femoral marrow, atrophy of the white pulp and extramedullary hematopoiesis of the spleen, atrophy of the thymus, auricular hypertrophy of the heart, extramedullary hematopoiesis and centriacinar telangiectasis of the liver, follicular degeneration of the ovary, and inflammation of the tail. The major treatment-related effects were not recovered at the end of 2-week recovery period. There were no adverse effects in the low and middle dose groups of both genders. In the present experimental conditions, the target organs were determined to be bone marrow, blood cells, spleen, liver, thymus, and heart. The no-observed-adverse-effect level was considered to be 0.013 mg/kg/day for males and 0.018 mg/kg/day for females.

Authors+Show Affiliations

College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea. toxkim@chonnam.ac.krNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15546689

Citation

Kim, J C., et al. "Subacute Toxicity Evaluation of a New Camptothecin Anticancer Agent CKD-602 Administered By Intravenous Injection to Rats." Regulatory Toxicology and Pharmacology : RTP, vol. 40, no. 3, 2004, pp. 356-69.
Kim JC, Shin DH, Kim SH, et al. Subacute toxicity evaluation of a new camptothecin anticancer agent CKD-602 administered by intravenous injection to rats. Regul Toxicol Pharmacol. 2004;40(3):356-69.
Kim, J. C., Shin, D. H., Kim, S. H., Kim, J. K., Park, S. C., Son, W. C., Lee, H. S., Suh, J. E., Kim, C. Y., Ha, C. S., & Chung, M. K. (2004). Subacute toxicity evaluation of a new camptothecin anticancer agent CKD-602 administered by intravenous injection to rats. Regulatory Toxicology and Pharmacology : RTP, 40(3), 356-69.
Kim JC, et al. Subacute Toxicity Evaluation of a New Camptothecin Anticancer Agent CKD-602 Administered By Intravenous Injection to Rats. Regul Toxicol Pharmacol. 2004;40(3):356-69. PubMed PMID: 15546689.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Subacute toxicity evaluation of a new camptothecin anticancer agent CKD-602 administered by intravenous injection to rats. AU - Kim,J C, AU - Shin,D H, AU - Kim,S H, AU - Kim,J K, AU - Park,S C, AU - Son,W C, AU - Lee,H S, AU - Suh,J E, AU - Kim,C Y, AU - Ha,C S, AU - Chung,M K, PY - 2004/07/05/received PY - 2004/11/18/pubmed PY - 2005/3/3/medline PY - 2004/11/18/entrez SP - 356 EP - 69 JF - Regulatory toxicology and pharmacology : RTP JO - Regul Toxicol Pharmacol VL - 40 IS - 3 N2 - The subacute toxicity of a new camptothecin anticancer agent, CKD-602, was investigated after 4-week repeated intravenous administration of the chemical in Sprague-Dawley rats. The test chemical was administered intravenously to rats at dose levels of 0, 0.003, 0.013, or 0.067 mg/kg/day for males and 0, 0.004, 0.018, or 0.089 mg/kg/day for females. At the end of the treatment period, 10 rats/sex/group were sacrificed. The remaining 5 rats/sex in the vehicle control and high dose groups continued the study without treatment for 2 weeks (recovery period). During the test period, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were examined. In both sexes of the high dose group, an increase in the incidence of abnormal clinical signs and paleness of the eyes, a reduction in the body weight gain, food consumption and urine protein, and an increase in the water consumption were observed. Hematological investigations revealed a decrease in the red blood cells, hemoglobin and hematocrit and an increase in the mean corpuscular volume, mean corpuscular hemoglobin, platelets, and reticulocytes in a dose-dependent manner. Serum total cholesterol and total protein values were lower in females than those of controls, but not in males. An increase in the heart and liver weights and a decrease in the thymus weight were also found. Histopathological alterations included an increase in the incidence of atrophy of the sternal marrow, atrophy, fibrosis and mast cell hyperplasia of the femoral marrow, atrophy of the white pulp and extramedullary hematopoiesis of the spleen, atrophy of the thymus, auricular hypertrophy of the heart, extramedullary hematopoiesis and centriacinar telangiectasis of the liver, follicular degeneration of the ovary, and inflammation of the tail. The major treatment-related effects were not recovered at the end of 2-week recovery period. There were no adverse effects in the low and middle dose groups of both genders. In the present experimental conditions, the target organs were determined to be bone marrow, blood cells, spleen, liver, thymus, and heart. The no-observed-adverse-effect level was considered to be 0.013 mg/kg/day for males and 0.018 mg/kg/day for females. SN - 0273-2300 UR - https://www.unboundmedicine.com/medline/citation/15546689/Subacute_toxicity_evaluation_of_a_new_camptothecin_anticancer_agent_CKD_602_administered_by_intravenous_injection_to_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0273-2300(04)00131-X DB - PRIME DP - Unbound Medicine ER -