Reproduction studies of carboplatin(III)--Intravenous administration to rats during the perinatal and lactation periods

Abstract

Carboplatin, an oncostatic drug, was administered intravenously to pregnant Crj: CD (Sprague-Dawley) rats from day 17 of gestation through day 21 of postpartum at dose levels of 1, 2 and 4 mg/kg/day. The summarized results obtained are as follows: 1. Maternal body weight gains were suppressed during the former part of the lactation period at carboplatin 2 mg/kg and higher. 2. Thymic weights were decreased and lung weights were increased in dams (F0) at carboplatin 2 mg/kg and higher. Further, ovarian weights were reduced in dams (F0) at carboplatin 4 mg/kg. 3. Carboplatin failed to affect the parturition of F0 dams. 4. Carboplatin did not affect the viability of newborns (F1), and postnatal differentiations, early behavioral developments, learning ability, motor activity or emotional development in F1 animals. 5. Carboplatin 4 mg/kg brought a suppression of pituitary weights after mating in F1 male rats and decreases of adrenal and genital organ weights at weaning in F1 female rats, but failed to affect their reproductive ability. 6. Influences on prenatal development were not apparently observed for F2 fetuses derived from F1 rats whose dams had ever received carboplatin during the perinatal and lactation periods. 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 dams and 2 mg/kg/day against their offspring.