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Title: Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals
Authors: Andersen, HR
Andersson, AM
Arnold, SF
Autrup, H
Barfoed, N
Beresford, NA
Bjerregaard, P
Christiansen, LB
Gissel, B
Hummel, R
Jorgensen, EB
Korsgaard, B
Le Guevel, R
Leffers, H
McLachlan, J
Moller, A
Nielsen, JB
Olea, N
Oles-Karasko, A
Pakdel, F
Pedersen, KL
Perez, P
Skakkeboek, NE
Sonnenschein, C
Soto, AM
Sumpter, JP
Thorpe, SM
Grandjean, P
Keywords: Estrogenic chemicals;Estrogens;Antiestrogens;Estrogenicity tests;Binding assay;Yeast;MCF-7;Vitellogenin
Issue Date: 1999
Publisher: National Institute of Environmental Health Science
Citation: Environ Health Perspect. 1999 Feb; 107(Suppl 1): 89-108
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 17β-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. 17β-Estradiol, 17α-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.
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