title: Validation study of OECD rodent uterotrophic assay for the assessment of estrogenic activity in Sprague-Dawley immature female rats.
abstract: The Organization for Economic Cooperation and Development (OECD) is developing a screening and testing method to identify estrogenic/antiestrogenic compounds. Based on these demands, phase 1 study for OECD uterotrophic assay was undertaken. The OECD is in the process of validating the assay results from international participating laboratories, which carried out this study with established environmental estrogenic compounds using designed protocols. The aim of this study was to provide data for validating the OECD uterotrophic assay using Sprague-Dawley immature female rats when testing with weak or partial estrogenic compounds. Ethinyl estradiol (EE) at 0.3 or 1 microg/kg/d, a positive control used in the present study, significantly increased both uterine wet and blotted weights. In the case of weak estrogenic compounds, the uterine wet weights were significantly increased by bisphenol A (BPA) at 300 mg/kg/d, nonylphenol (NP) at 80 mg/kg/d, genistein (GN) at 35 mg/kg/d, and methoxychlor (MXC) at 500 mg/kg/d. In addition, the increase in uterine blotted weights also showed a similar pattern to that of uterine wet weights. However, both 1,1,1-trichloro-2,2-bis(p-chlorphenyl)ethane (o,p-DDT) and dibutyl phthalate (DBP) did not affect uterus (wet and blotted) weights at doses of 100 and 500 mg/kg/d. These results suggest that the increase in uterine weights should be considered useful as a sensitive endpoint for detecting weak estrogenic compounds in 3-d rodent uterotrophic assay. However, further combination studies using surrogate biomarkers may be needed to improve the sensitivity of this assay for the detection of weak estrogenic compounds, such as o,p-DDT.
authors.affiliation: Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University, Jangjun-dong, Gumjung-ku, Korea.
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Tae Seok
authors.initials: TS
authors.lastname: Kang
authors.forename: Il Hyun
authors.initials: IH
authors.lastname: Kang
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Kim
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Moon
authors.forename: In Young
authors.initials: IY
authors.lastname: Kim
authors.forename: Hoyun
authors.initials: H
authors.lastname: Ki
authors.forename: Kui Lea
authors.initials: KL
authors.lastname: Park
authors.forename: Byung Mu
authors.initials: BM
authors.lastname: Lee
authors.forename: Sun Dong
authors.initials: SD
authors.lastname: Yoo
authors.forename: Soon-Young
authors.initials: SY
authors.lastname: Han
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D001681:Biological Assay / Q000379:methods* / Q000592:standards; D003634:DDT / Q000633:toxicity; D003993:Dibutyl Phthalate / Q000633:toxicity; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D019833:Genistein / Q000633:toxicity; D008731:Methoxychlor / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D014599:Uterus / Q000187:drug effects* / Q000473:pathology; D014621:Vagina / Q000187:drug effects / Q000473:pathology; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D003634:DDT; D003993:Dibutyl Phthalate; D004967:Estrogens; D019833:Genistein; D008731:Methoxychlor; D010636:Phenols; C025256:nonylphenol; C016340:o,p'-DDT; C006780:bisphenol A; D000098826:Bisphenol A Compounds