[Toxicity studies of paclitaxel. (III)--Six-month intermittent intravenous toxicity in rats].
Paclitaxel, an antineoplastic agent, was intravenously given to Crj:CD (SD) rats of both sexes at 0 (saline), 0 (vehicle), 0.3 (low dose), 1.0 (intermediate dose) and 3.3 (high dose) mg/kg at seven-day interval over a six-month period (total of 27 doses) to investigate its repeated dose toxicity. The results obtained are summarized as follows: 1. No deaths occurred in this study. Vehicle-related salivation was seen for some high dose and vehicle control rats. Soiling of the perigenital region was observed for some high dose females. 2. Red blood cell count, hemoglobin, hematocrit and white blood cell count were decreased for high dose rats. Reticulocyte count was increased and relative neutrophil count was decreased for high dose males. 3. Relative erythroid and myeloid cell count were decreased for high dose rats in bone marrow smear examinations. 4. Bone marrow hypoplasia and splenic hemosiderosis were observed for high dose rats, and thymic atrophy and lymphoid depletion were seen for some high dose males. Based on the these results, the no-toxic effect dose of paclitaxel was estimated to be 1.0 mg/kg in rats under this study condition.
Kadota
T
T
Preclinical Research Laboratories, Bristol-Myers Squibb K. K., Aichi, Japan.
Kondoh
H
H
Chikazawa
H
H
Kuroyanagi
K
K
Hattori
N
N
Ishikawa
K
K
Kawano
S
S
Sakakura
K
K
Koizumi
S
S
Hiraiwa
E
E
D000818:Animals; D001284:Atrophy; D001772:Blood Cell Count / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002452:Cell Count / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D006486:Hemosiderosis / Q000139:chemically induced; D007275:Injections, Intravenous; D008221:Lymphoid Tissue / Q000187:drug effects; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013158:Splenic Diseases / Q000139:chemically induced; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology
D017239:Paclitaxel