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The use of metabolising systems for in vitro testing of endocrine disruptors

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Author: Jacobs, M.N. · Janssens, W. · Bernauer, U. · Brandon, E. · Coecke, S. · Combes, R. · Edwards, P. · Freidig, A. · Freyberger, A. · Kolanczyk, R. · Mc Ardie, C. · Mekenyan, O. · Schmieder, P. · Schrader, T. · Takeyoshi, M. · Burg, B. van der
Type:article
Date:2008
Institution: TNO Kwaliteit van Leven
Source:Current Drug Metabolism, 8, 9, 796-826
Identifier: 241179
doi: doi:10.2174/138920008786049294
Keywords: Androgenicity · Cytochrome P450 · Endocrine active substances · Endocrine disruption · Estrogenicity · Metabolism · 2,2 bis(1,4 hydroxyphenyl) 1,1,1 trichloroethane · 2,3,7,8 tetrachlorodibenzo para dioxin · Animals · Biotransformation · Cell Proliferation · Endocrine Disruptors · Endocrine System · Enzyme Induction · Humans · Methoxychlor · Skin · Steroids · Transcriptional Activation

Abstract

Legislation and prospective legislative proposals in for instance the USA, Europe, and Japan require, or may require that chemicals are tested for their ability to disrupt the hormonal systems of mammals. Chemicals found to test positive are considered to be endocrine active substances (EAS) and may be putative endocrine disruptors (EDs). To date, there is still little or no experience with incorporating metabolic and toxicokinetic aspects into in vitro tests for EAS. This is a situation in sharp contrast to genotoxicity testing, where in vitro tests are routinely conducted with and without metabolic capacity. Originally prepared for the Organisation of Economic Cooperation and Development (OECD), this detailed review paper reviews why in vitro assays for EAS should incorporate mammalian systems of metabolism and metabolic enzyme systems, and indicates how this could be done. The background to ED testing, the available test methods, and the role of mammalian metabolism in the activation and the inactivation of both endogenous and exogenous steroids are described. The available types of systems are compared, and the potential problems in incorporating systems in in vitro tests for EAS, and how these might be overcome, are discussed. Lastly, some recommendations for future activities are made. © 2008 Bentham Science Publishers Ltd. Chemicals / CAS: 2,3,7,8 tetrachlorodibenzo para dioxin, 1746-01-6; aroclor 1254, 11097-69-1; beta naphthoflavone, 6051-87-2; methoxychlor, 72-43-5; tamoxifen, 10540-29-1; vinclozolin, 50471-44-8; Endocrine Disruptors; Methoxychlor, 72-43-5; Steroids