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  4. Metabolism and pharmacokinetics of zearalenone following oral and intravenous administration in juvenile female pigs
 
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2017
Journal Article
Title

Metabolism and pharmacokinetics of zearalenone following oral and intravenous administration in juvenile female pigs

Abstract
Zearalenone (ZEN) is a well-studied mycotoxin whose potent estrogenic properties have been used by international regulatory bodies to set health-based guidance values for ZEN exposure in grain-based foods from changes in hormonally responsive tissues of juvenile female pigs. The role of metabolism in determining estrogenic responses in vivo is a major uncertainty in inter-species extrapolation to humans and in assessing the potential for added susceptibility in sensitive subpopulations. This study evaluated the metabolism of ZEN and pharmacokinetics in ∼2 month-old female pigs using oral and intravenous dosing. The absolute bioavailability (AUCoral/AUCIV) of receptor-active ZEN aglycone was 1.8 ± 0.80%, consistent with extensive pre-systemic Phase II conjugation. Reductive metabolism to a-zearalenol (a-ZEL) was extensive, with smaller amounts of v-ZEL. When combined with its higher binding affinity, relative to ZEN and v-ZEL, a-ZEL was the predominant contributor to total estrogen receptor ligand activity (∼90%) after oral dosing with ZEN. The apparent similarities of reductive and Phase II conjugation metabolism of ZEN between pigs and humans support the use of juvenile female pigs as a sensitive model for risk assessments of estrogenic effects from dietary ZEN.
Author(s)
Fleck, S.C.
Churchwell, M.I.
Doerge, D.R.
Journal
Food and Chemical Toxicology : FCT  
Open Access
DOI
10.1016/j.fct.2017.05.048
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English
Fraunhofer-Institut für Molekularbiologie und Angewandte Oekologie IME  
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