[Reproductive and developmental toxicity studies of paclitaxel. (I)--Intravenous administration to rats prior to and in the early stages of pregnancy].

Paclitaxel, an antineoplastic agent, was administered intravenously to Crj: CD (SD) rats daily at dose levels of 0 (saline and vehicle), 0.1, 0.3 and 1.0 mg/kg for 63 days prior to mating and during the mating period in males, and for 14 days prior to mating and during the mating period as well as day 0 to day 7 of gestation in females. Results were as follows: 1. Body weight gains were shown a tendency to hasten in vehicle-treated male rats associated with the increased food consumption. However, the vehicle-treated group had no effect in the other parameters that were measured in this study when compared to the saline-treated group. 2. 1.0 mg/kg paclitaxel caused suppression of the body weight gains accompanied by the decreased food consumption in either male or female rats. 3. Adrenal and ovarian weights were decreased in 1.0 mg/kg dams at term. 4. The fertility indices in both sexes of 1.0 mg/kg were lower than the saline-treated group. However, the copulation indices in both sexes in 1.0 mg/kg rats were comparable to those of the saline-treated group. 5. Decreases in the number of corpora lutea, implantations and live fetuses or increases in the number of empty implantation sites and total embryo-fetal deaths were observed in 1.0 mg/kg dams. However, the fetal weights, crown-rump distances and tail lengths in live fetuses were not affected by paclitaxel treatment. Based on the reproductive and developmental indices, the no toxic-effect dose level of paclitaxel is 0.3 mg/kg/day for parent animals and their fetuses.