Collaborative work on evaluation of ovarian toxicity. 14) Two- or four-week repeated-dose studies and fertility study of atrazine in female rats.
To investigate the optimal administration period for evaluating ovarian toxicity that reflects abnormal female fertility in the repeated dose toxicity study, atrazine, a potent herbicide with endocrine-disrupting activity, was administered to female Sprague-Dawley (Slc:SD) rats for two or four weeks at doses of 3, 30 or 300 mg/kg for the repeated dose toxicity study, and at doses of 3, 30 or 100 mg/kg for the female fertility study from two weeks before mating to Day 7 of gestation. In the two-week repeated dose toxicity study, prolongation of diestrus and histopathological findings such as loss of the currently formed corpora lutea, decrease in the numbers of previously formed corpora lutea, increase in large-sized atretic follicles, and swelling of the previously formed luteal cells were observed in the 300 mg/kg group, suggesting that atrazine had an anovulatory effect through suppression of the luteinizing hormone surge. In the female fertility study, copulation failure caused by prolongation of diestrus was observed in one animal in the 100 mg/kg group, which could be due to the anovulatory effect of atrazine. It is demonstrated that the effect of atrazine on female fertility can be assessed by detailed histopathological examination of ovaries in a two-week repeated dose toxicity study, provided the appropriate dose levels are selected.
Shibayama
Hiroshi
H
Toxicology Department, Nippon Shinyaku Co., Ltd., Minami-ku, Kyoto, Japan. h.shibayama@po.nippon-shinyaku.co.jp
Kotera
Takashi
T
Shinoda
Yasuhiko
Y
Hanada
Tomohiko
T
Kajihara
Tsutomu
T
Ueda
Makoto
M
Tamura
Hideyuki
H
Ishibashi
Seitarou
S
Yamashita
Yasuhiro
Y
Ochi
Seishi
S
D000818:Animals; D001280:Atrazine / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003307:Copulation / Q000187:drug effects; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004334:Drug Administration Schedule; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects*; D006540:Herbicides / Q000008:administration & dosage / Q000633:toxicity*; D007564:Japan; D008297:Male; D009929:Organ Size / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; 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*; D015430:Weight Gain / Q000187:drug effects
D006540:Herbicides; D018809:Proliferating Cell Nuclear Antigen; D001280:Atrazine