REPRODUCTION STUDIES OF VP 16-213 (I) : Oral administration to rats prior to and in the early stages of pregnancy

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to male Crj: CD (Sprague-Dawley) rats for 64 days and to female rats of the same strain for 15 days prior to mating at dose levels of l, 3 and l0 mg/kg /day. These animals were then mated under the consecutive administra...

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Bibliographic Details
Published in:Journal of toxicological sciences 1986/04/25, Vol.11(SupplementI), pp.177-194
Main Authors: TAKAHASHI, Norimitsu, KAI, Shuichi, KOHMURA, Hisashi, ISHIKAWA, Katsumi, KUROYANAGI, Kohji, HAMAJIMA, Yoshinori, OHTA, Satoshi, KADOTA, Toshihito, KAWANO, Shigeo, OHTA, Keiko
Format: Article
Language:eng ; jpn
Subjects:
Administration, Oral
Animals
Body Weight - drug effects
Eating - drug effects
Embryonic and Fetal Development - drug effects
Etoposide - administration & dosage
Etoposide - toxicity
Female
Male
Pregnancy
Pregnancy, Animal - drug effects
rat
Rats
Rats, Inbred Strains
Reproduction - drug effects
Testis - drug effects
Thymus Gland - drug effects
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Summary:VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to male Crj: CD (Sprague-Dawley) rats for 64 days and to female rats of the same strain for 15 days prior to mating at dose levels of l, 3 and l0 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. VP 10 mg/kg suppressed the body weight increase in females from day 8 of pre-mating through day 20 of gestation, but did not affect the body weight in males. 2. VP 10 mg/kg decreased the organ weights of testes, epididymides and thymus in males and induced atrophy of these organs macroscopically, but did not affect their reproductive performances. 3. As for fetuses, VP 10 mg/kg elevated the mortality and induced anophthalmia, microphthalmia and dilated lateral ventricles, as well as suppressed their growth and the ossification processes of sternums, sacral and coccygeal vertebrae, metacarpus, thoracic vertebrae and pubis. 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 parent rats of both sexes and their offspring.
ISSN:0388-1350
1880-3989
DOI:10.2131/jts.11.SupplementI_177