Collaborative work on evaluation of ovarian toxicity. 4) Two- or four-week repeated dose study of 4-vinylcyclohexene diepoxide in female rats.
To determine the optimal administration period for evaluation of ovarian toxicity of 4-vinylcyclohexene diepoxide (VCD), VCD was intraperitoneally administered to female Sprague-Dawley rats at 0 (Control), 5, 20 and 80 mg/kg once a day for 2 or 4 weeks (2- or 4-week study). To identify small follicles, serial sections of the ovaries were stained with routine hematoxylin and eosin (HE) and proliferating cell nuclear antigen (PCNA) immunohistochemistry. In the 4-week study, decrease in small follicles was observed in the ovaries at 20 and 80 mg/kg. In the 2-week study, the same change was also observed at 80 mg/kg. Identification of small follicles using PCNA-stained slides was easier than that using HE-stained slides. In conclusion, histopathological findings in the ovaries are important for evaluation of female reproductive toxicity of VCD, and ovarian toxicity of VCD can be detected by administration for 2 weeks at an appropriate dose level. Furthermore, PCNA immunohistochemistry is effective for evaluation of small follicle destruction in chemical-induced ovarian toxicity.
Ito
Atsushi
A
Drug Research Section III, Fukushima Research Laboratories, R&D Department, Toa Eiyo Ltd., Iizaka, Fukushima, Japan. itou.atushi@toaeiyo.co.jp
Mafune
Naomi
N
Kimura
Takashi
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D053138:Cyclohexenes / Q000008:administration & dosage / Q000633:toxicity*; D004622:Embryo, Mammalian / Q000187:drug effects / Q000503:physiopathology; D047108:Embryonic Development / Q000187:drug effects / Q000502:physiology; D005260:Female; D007274:Injections, Intraperitoneal; D007564:Japan; D008136:Longevity / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000187:drug effects* / Q000473:pathology; D011247:Pregnancy; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D055818:Public-Private Sector Partnerships; D051381:Rats; D017207:Rats, Sprague-Dawley; D012958:Societies, Scientific; D018675:Toxicity Tests / Q000379:methods*; D014753:Vinyl Compounds / Q000008:administration & dosage / Q000633:toxicity*; D015262:Xenobiotics
D015415:Biomarkers; D002273:Carcinogens; D053138:Cyclohexenes; D018809:Proliferating Cell Nuclear Antigen; D014753:Vinyl Compounds; D015262:Xenobiotics; C012606:4-vinyl-1-cyclohexene dioxide