title: Comparison of short-term estrogenicity tests for identification of hormone-disrupting chemicals.
abstract: The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17beta++-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17beta-Estradiol, 17alpha-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds--tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p'-DDT, p,p'-DDE, endosulfan, chlomequat chloride, and ethanol--varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods.
authors.affiliation: Department of Environmental Medicine, Odense University, Denmark. hr.andersen@winsloew.ou.dk
authors.forename: H R
authors.initials: HR
authors.lastname: Andersen
authors.forename: A M
authors.initials: AM
authors.lastname: Andersson
authors.forename: S F
authors.initials: SF
authors.lastname: Arnold
authors.forename: H
authors.initials: H
authors.lastname: Autrup
authors.forename: M
authors.initials: M
authors.lastname: Barfoed
authors.forename: N A
authors.initials: NA
authors.lastname: Beresford
authors.forename: P
authors.initials: P
authors.lastname: Bjerregaard
authors.forename: L B
authors.initials: LB
authors.lastname: Christiansen
authors.forename: B
authors.initials: B
authors.lastname: Gissel
authors.forename: R
authors.initials: R
authors.lastname: Hummel
authors.forename: E B
authors.initials: EB
authors.lastname: Jørgensen
authors.forename: B
authors.initials: B
authors.lastname: Korsgaard
authors.forename: R
authors.initials: R
authors.lastname: Le Guevel
authors.forename: H
authors.initials: H
authors.lastname: Leffers
authors.forename: J
authors.initials: J
authors.lastname: McLachlan
authors.forename: A
authors.initials: A
authors.lastname: Møller
authors.forename: J B
authors.initials: JB
authors.lastname: Nielsen
authors.forename: N
authors.initials: N
authors.lastname: Olea
authors.forename: A
authors.initials: A
authors.lastname: Oles-Karasko
authors.forename: F
authors.initials: F
authors.lastname: Pakdel
authors.forename: K L
authors.initials: KL
authors.lastname: Pedersen
authors.forename: P
authors.initials: P
authors.lastname: Perez
authors.forename: N E
authors.initials: NE
authors.lastname: Skakkeboek
authors.forename: C
authors.initials: C
authors.lastname: Sonnenschein
authors.forename: A M
authors.initials: AM
authors.lastname: Soto
mesh_terms: D003634:DDT / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism / Q000633:toxicity*; D000431:Ethanol / Q000633:toxicity; D000077267:Fulvestrant; D006801:Humans; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014819:Vitellogenins / Q000096:biosynthesis
chemical_list: D004785:Environmental Pollutants; D004967:Estrogens; D011960:Receptors, Estrogen; D014819:Vitellogenins; D013629:Tamoxifen; D000077267:Fulvestrant; D000431:Ethanol; D004958:Estradiol; D003634:DDT