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. 1999 Feb;107(Suppl 1):89–108. doi: 10.1289/ehp.99107s189

Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals

Helle Raun Andersen, Anna-Maria Andersson, Steven F Arnold, Herman Autrup, Marianne Barfoed, Nicola A Beresford, Poul Bjerregaard, Lisette B Christiansen, Birgitte Gissel, René Hummel, Eva Bonefeld Jørgensen, Bodil Korsgaard, Remy Le Guevel, Henrik Leffers, John McLachlan, Anette Møller, Jesper Bo Nielsen, Nicolas Olea, Anita Oles-Karasko, Farzad Pakdel, Knud L Pedersen, Pilar Perez, Niels Erik Skakkebœk, Carlos Sonnenschein, Ana M Soto, John P Sumpter, Susan M Thorpe, Philippe Grandjean
PMCID: PMC1566352  PMID: 10229711

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.

Keywords: estrogenic chemicals, estrogens, antiestrogens, estrogenicity tests, binding assay, yeast, MCF-7, vitellogenin

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Selected References

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