title: Ovariectomized mouse uterotrophic assay of 36 chemicals.
abstract: The concern over endocrine disruptors prompted international establishment of a strategic framework for the identification of the estrogenic compounds. OECD has launched the Conceptual Framework tool box containing various screening and testing methods including the uterotrophic assay. The (anti)estrogenicity of 36 chemicals suspected to be estrogen-receptor interactive by in silico and/or in vitro screening in the Extended Scheme for Endocrine Disruptor Screening and Testing of the  Ministry of Health, Labour and Welfare, Japan, were monitored by the uterotrophic assay using C57BL/6J ovariectomized adult female mice after a 7-day exposure by oral gavage (po) and subcutaneous injection (sc). Ethynyl estradiol was used as reference for agonist and antagonist detection. In addition, Bisphenol A (sc) and Genistein (po) were tested for the comparison to rat assays. Among the 36, 2-[Bis(4-hydroxy-phenyl)methyl]benzylalcohol, 2,2',4,4'-Tetrahydroxybenzophenone, 2,4-Dihydroxybenzophenone, 3,3',5-Triiodothyroacetic acid, New fuchsin and alpha-Naphtholbenzein, showed both estrogenic agonistic and antagonistic activities; first two showed U-shaped dose-response in antagonistic studies. N,N-Diphenyl-p-phenylenediamine, 2,2'-Dihydroxy-4,4'-dimethoxybenzophenone, n-Butyl 4-hydroxybenzoate,  and Reserpine were agonistic by sc. Benzo [a] pyrene, Benz [a] anthracene, Dibenz [a,h] anthracene,  2-(2H-Benzotriazol-2-yl)-4,6-di(t-pentyl)phenol, Rosemarinic acid, meta-Thymol, 6-Gingerol,  Colchicine, Malachite green base, Fenbuconazole, and Lead acetate were antagonistic. The rest, i.e. n-Heptyl 4-hydroxybenzoate, Tetrazolium violet, Pravastatin sodium salt, Physostigmine, salicylate (1:1), Nordihydroguaiaretic acid, o-Cresolphthalein, 1,3-Dinitrobenzene, C.I. Pigment orange, Tetrabromobis-phenol-A, 2-Hydroxy-4-methoxybenzophenone, Ethylparaben, Propyl p-hydroxybenzoate, Kaempferol, 2-(2-Benzotriazolyl)-p-cresol and Phenolphthalein were negative for both effects. Taking together with in silico/ in vitro screening, the result suggested that the ovariectomized mouse uterotrophic bioassay has sufficient performance comparable to rat for the screening of (anti)estrogenicity of various chemicals.
authors.affiliation: Hatano Research Institute, Food and Drug Safety Center, Kanagawa, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Ohta
authors.forename: Atsuya
authors.initials: A
authors.lastname: Takagi
authors.forename: Hideo
authors.initials: H
authors.lastname: Ohmukai
authors.forename: Hideki
authors.initials: H
authors.lastname: Marumo
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ono
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsushima
authors.forename: Tohru
authors.initials: T
authors.lastname: Inoue
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ono
authors.forename: Jun
authors.initials: J
authors.lastname: Kanno
mesh_terms: D000818:Animals; D001681:Biological Assay / Q000379:methods*; D052244:Endocrine Disruptors / Q000633:toxicity*; D020847:Estrogen Receptor Modulators / Q000633:toxicity*; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D014599:Uterus / Q000187:drug effects* / Q000254:growth & development
chemical_list: D052244:Endocrine Disruptors; D020847:Estrogen Receptor Modulators; D004967:Estrogens