[Toxicity studies of paclitaxel. (I)--Single dose intravenous toxicity in rats].
Paclitaxel, an antineoplastic agent, was given to Crj: CD (SD) rats of both sexes at 38, 50, 65 and 85 mg/kg by single intravenous administration to investigate its acute toxicity. The results obtained are summarized as follows: 1. Tachypnea and decreased activity with prone position were noted for vehicle and all paclitaxel groups, and alopecia for all paclitaxel groups. 2. Deaths occurred for one out of 5 males and 2 out of 5 females at 85 mg/kg. One female died of respiratory insufficiency induced by vehicle on Day 0. One female and one male died of the systemic toxicity of paclitaxel such as hypoplasia of the bone marrow and lymphoid depletion of lymphatic organs on Days 6 and 12, respectively. 3. On Days 4 and 5, all paclitaxel groups showed decreases of reticulocyte and white blood cell counts, as well as decrease of differential count of neutrophils. These changes were generally recovered by a week after dosing. 4. Histopathological examinations revealed atrophy of the thymic medulla, hypoplasia of the bone marrow and lymphoid depletion of the spleen for a few males at 85 mg/kg, and hypospermatogenesis and tubular atrophy of the testes for all paclitaxel groups. Based on these results, 85 mg/kg of paclitaxel was lethal to rats, and hematopoietic, lymphoid and male reproductive systems were primarily affected under this condition.
Kadota
T
T
Preclinical Research Laboratories, Bristol-Myers Squibb K. K., Aichi, Japan.
Chikazawa
H
H
Kondoh
H
H
Ishikawa
K
K
Kawano
S
S
Kuroyanagi
K
K
Hattori
N
N
Sakakura
K
K
Koizumi
S
S
Hiraiwa
E
E
D000505:Alopecia / Q000139:chemically induced; D000818:Animals; D001284:Atrophy; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013091:Spermatogenesis / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology
D017239:Paclitaxel