TOXICITY STUDIES OF PACLITAXEL (II) : One-month intermittent intravenous toxicity in rats

Autor: Toshihito KADOTA, Hirotaka CHIKAZAWA, Hiroshi KONDOH, Katsumi ISHIKAWA, Shigeo KAWANO, Kohji KUROYANAGI, Norimichi HATTORI, Kayo SAKAKURA, Shigeru KOIZUMI, Eiko HIRAIWA, Hisashi KOHMURA, Shuichi KAI, Norimitsu TAKAHASHI
Rok vydání: 1994
Předmět:
Zdroj: The Journal of Toxicological Sciences. 19:11-34
ISSN: 1880-3989
0388-1350
Popis: Paclitaxel, an antineoplastic agent, was intravenously given to Crj:CD (SD) rats of both sexes at 0 (saline), 0 (vehicle), 1.0 (low dose), 3.3 (intermediate dose) and 10.0 (high dose) mg/kg at five-day interval over one-month period (6 times in total) to investigate its repeated dose toxicity and the reversibility of toxic effects. The results obtained are summarized as follows: 1. Decreased activity with prone position was observed for high dose and vehicle groups, and alopecia was seen for many high dose rats. Body weight gain and food intake were suppressed for high and intermediate dose groups. No deaths occurred. 2. Red blood cell count, hemoglobin, hematocrit, white blood cell count, relative neutrophil count, platelet count and reticulocyte count were decreased for high dose groups. Red blood cells count was also decreased for intermediate dose groups. 3. Thymic atrophy, splenic hematopoiesis, bone marrow hypoplasia, testicular atrophy with suppression of spermatogenesis and tubular atrophy, and epididymal atrophy were observed for high dose rats. 4. Above-described changes excluding the findings on the testis and epididymis for high dose rats were shown to be generally reversible. Based on these results, the no-toxic effect dose of paclitaxel was estimated to be 1.0 mg/kg in rats under this study condition.
Databáze: OpenAIRE