Validation study of OECD rodent uterotrophic assay for the assessment of estrogenic activity in Sprague-Dawley immature female rats.
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.
Kim
Hyung Sik
HS
Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University, Jangjun-dong, Gumjung-ku, Korea.
Kang
Tae Seok
TS
Kang
Il Hyun
IH
Kim
Tae Sung
TS
Moon
Hyun Ju
HJ
Kim
In Young
IY
Ki
Hoyun
H
Park
Kui Lea
KL
Lee
Byung Mu
BM
Yoo
Sun Dong
SD
Han
Soon-Young
SY
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
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