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Investigating natural and xenohormones with the BG1LUC4E2 CALUX BIOASSAY: estrogenicity of pure compounds and mixtures - Abstract @ Dioxin 2016
Boekbijdrage - Boekhoofdstuk Conferentiebijdrage
EPs (Emerging Pollutants) such as EDCs (Endocrine Disrupting Chemicals) are of special concern because they interfere with hormone biosynthesis, metabolism or action, resulting in a deviation from normal homeostatic control or reproduction. The European Commission added 15 chemicals to the watch
list of the Environmental Quality Standards Directive (2008/105/EC and 2013/39/EU). For the first time pharmaceuticals are proposed including, EE2 (17 α-ethinylestradiol, the synthetic steroidal hormone used in birth control pills) and E2 (17 β-estradiol, the endogenous female sex hormone).
Although instrumental analysis can be used to identify and quantify known EDCs, hazard assessment based on chemical monitoring is complicated, because EDCs are structurally highly distinct compounds and mixture interactions have to be taken into account. Estrogenic activities can be measured by using a CALUX (Chemical Activated Luciferase Gene Expression) analysis. The mechanism-based, sensitive in vitro trans-activational reporter gene assay, BG1Luc4E2 cell line, provides useful information about the total estrogenic potency of complex mixtures of chemicals in environmental samples and is thus able to account for both (un)known active compounds and mixture interactions in a sample.
In this study, 21 pure compounds and 2 mixtures with potential endocrine activity were screened and characterized. The full dose response curve was fitted with a Hill equation to quantify and compare endocrine potencies. The validity of the theoretical prediction of the activity of mixtures by the
Concentration Addition (CA) principle was investigated.
The sex steroids (their derivatives and synthetic versions) and the plastic monomers were identified as the most potent agonists, followed by the pesticides. Some of these exerted both agonist and antagonist activity. The glucocorticoids, phytohormones and pharmaceuticals were identified as antagonists of the endocrine receptors. The observed activities matched with the categories based on the functions and types of the compounds. The CA principle was shown to severely underestimate the potencies of the mixtures, when compared to the experimental observations.
list of the Environmental Quality Standards Directive (2008/105/EC and 2013/39/EU). For the first time pharmaceuticals are proposed including, EE2 (17 α-ethinylestradiol, the synthetic steroidal hormone used in birth control pills) and E2 (17 β-estradiol, the endogenous female sex hormone).
Although instrumental analysis can be used to identify and quantify known EDCs, hazard assessment based on chemical monitoring is complicated, because EDCs are structurally highly distinct compounds and mixture interactions have to be taken into account. Estrogenic activities can be measured by using a CALUX (Chemical Activated Luciferase Gene Expression) analysis. The mechanism-based, sensitive in vitro trans-activational reporter gene assay, BG1Luc4E2 cell line, provides useful information about the total estrogenic potency of complex mixtures of chemicals in environmental samples and is thus able to account for both (un)known active compounds and mixture interactions in a sample.
In this study, 21 pure compounds and 2 mixtures with potential endocrine activity were screened and characterized. The full dose response curve was fitted with a Hill equation to quantify and compare endocrine potencies. The validity of the theoretical prediction of the activity of mixtures by the
Concentration Addition (CA) principle was investigated.
The sex steroids (their derivatives and synthetic versions) and the plastic monomers were identified as the most potent agonists, followed by the pesticides. Some of these exerted both agonist and antagonist activity. The glucocorticoids, phytohormones and pharmaceuticals were identified as antagonists of the endocrine receptors. The observed activities matched with the categories based on the functions and types of the compounds. The CA principle was shown to severely underestimate the potencies of the mixtures, when compared to the experimental observations.
Boek: Dioxin 2016, 36th International Symposium on Halogenated Persistent Organic Pollutants
Volume: 78
Aantal pagina's: 4
Jaar van publicatie:2016
Trefwoorden:CALUX, Xenohormones, BG1Luc4E2, Estrogenicity