Enhanced OECD TG 407 in detection of endocrine-mediated effects of 4,4'-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol.
The purpose of this study was to investigate whether the estrogenic effects were detected in the enhanced TG 407 if the estrogenic property was not so strong in the uterotrophic assay. The estrogenic property of 4,4'-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol in the uterotrophic assay was slightly stronger than that of genistein or nonylphenol, but weaker than that of ethinyl estradiol. We performed a 28-day repeated-dose toxicity study (enhanced OECD test guideline No. 407) on 4,4'-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol based on the OECD draft protocol. The test chemical, administered orally at doses of 0, 10, 50, and 250 mg/kg per day for at least 28 days, caused such estrogenic effects as abnormal estrous cycle, increased ovarian follicles, increased uterine epithelial height, and vaginal mucification in the 50 and/or 250 mg/kg groups. Moreover, follicular epithelial cell hyperplasia of the thyroid was detected in all male rats given the test chemical and in female rats in the 250 mg/kg group. It was concluded that the estrogenic effects were detected in growing rats given 4,4'-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol, and thyroid dysfunction was also observed as the endocrine-mediated effects.
Umano
Takaaki
T
Chemicals Evaluation and Research Institute, 1-4-25 Kouraku, Bunkyo-ku, Tokyo 112-0004, Japan. umano-takaaki@ceri.jp
Miyata
Katsumi
K
Minobe
Yasushi
Y
Yamasaki
Kanji
K
D000818:Animals; D001559:Benzhydryl Compounds / Q000145:classification / Q000633:toxicity*; D001681:Biological Assay; D001835:Body Weight / Q000187:drug effects; D019963:Clinical Chemistry Tests; D052244:Endocrine Disruptors / Q000145:classification / Q000633:toxicity*; D030762:Estrous Cycle / Q000187:drug effects* / Q000502:physiology; D005062:European Union; D005260:Female; D005836:Genitalia, Female / Q000187:drug effects* / Q000473:pathology; D005837:Genitalia, Male / Q000187:drug effects* / Q000473:pathology; D017408:Guidelines as Topic; D006403:Hematologic Tests; D007390:International Agencies; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000187:drug effects / Q000473:pathology; D000098833:Bisphenol F Compounds
D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; C558701:4,4'-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol; D000098833:Bisphenol F Compounds