TY - JOUR
T1 - The use of metabolising systems for in vitro testing of endocrine disruptors
AU - Jacobs, Miriam
AU - Janssens, W.
AU - Bernauer, U.
AU - Brandon, E.
AU - Coecke, S.
AU - Combes, R.
AU - Edwards, P.
AU - Freidig, A.
AU - Freyberger, A.
AU - Kolanczyk, R.
AU - Mc Ardie, C.
AU - Mekenyan, O.
AU - Schmieder, P.
AU - Schrader, T.
AU - Takeyoshi, M.
AU - van der Burg, B.
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
KW - Androgenicity
KW - Cytochrome P450
KW - Endocrine active substances
KW - Endocrine disruption
KW - Estrogenicity
KW - Metabolism
UR - http://www.scopus.com/inward/record.url?scp=58149333545&partnerID=8YFLogxK
U2 - 10.2174/138920008786049294
DO - 10.2174/138920008786049294
M3 - Review article
C2 - 18855613
AN - SCOPUS:58149333545
SN - 1389-2002
VL - 9
SP - 796
EP - 826
JO - Current Drug Metabolism
JF - Current Drug Metabolism
IS - 8
ER -