REPRODUCTION STUDIES OF VP 16-213 (IV) : Oral administration to rats during the perinatal and lactation periods

Abstract

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to female Crj: CD (Sprague-Dawley) rats from day 17 of gestation through postpartum day 20 at dose levels of 1, 3 and 10 mg/kg/day. The summarized results obtained are as follows: 1. VP 10 mg/kg induced thymic atrophy in dams. 2. VP failed to affect the parturition of dams. 3. VP 10 mg/kg lowered the viability of newborns (F₁) on postpartum day 3 and increased the days required for descending of testes, but failed to affect the growth of genital organs, learing ability, motility, motor activity or emotional development. 4. VP 10 mg/kg brought a transient suppression of body weight increase in pregnant F₁ rats, but failed to affect their reproductive ability and parturition. 5. F₂ newborns derived from F₁ rats whose dams had ever received VP during the prenatal and lactation periods showed no changes in observation items at birth. 6. Long-term rearing F₁ rats derived from VP-treated dams manifested no delayed toxicity including carcinogenicity. Based on these results, the no-effect dose level of VP under the present experimental condition was estimated to be 3 mg/kg/day against dams and their offspring.