Reproduction studies of carboplatin (I)--Intravenous administration to rats prior to and in the early stages of pregnancy

Abstract

Carboplatin, an oncostatic drug, was administered intravenously to male Crj: CD (Sprague-Dawley) rats for 63 days and to female rats of the same strain for 14 days prior to mating at dose levels of 1, 2 and 4 mg/kg/day. These animals were then mated under the consecutive administration of this drug and the females confirmed to be copulated were further dosed from day 0 through 7 of gestation. The summarized results obtained are as follows: 1. Carboplatin 2 mg/kg and higher suppressed body weight gains accompanied by the decreases in food and water consumption in male rats. Further, body weight gains were suppressed in female rats followed by the decreases in food consumption at the same dose levels. 2. Though there were no differences between dosed animals and controls regarding the organ weights, the incidence of necrosis of the tails around the injection site was increased in male rats at 4 mg/kg. 3. Carboplatin failed to affect the reproductive ability of both sexes. 4. As for fetuses, the mortality was elevated at 2 mg/kg and higher and the number of live fetuses reduced at 4 mg/kg, but the influences on prenatal development were not apparently observed for live fetuses even at the highest dose level. Based on these results, the no-effect dose level of carboplatin under the present experimental condition was estimated to be 1 mg/kg/day against parent rats of both sexes and their offspring.