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

: Fleck, S.C.; Churchwell, M.I.; Doerge, D.R.


Food and Chemical Toxicology : FCT 106, Part A (2017), pp.193-201
ISSN: 0278-6915
ISSN: 1873-6351
Journal Article
Fraunhofer IME ()

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 α-zearalenol (α-ZEL) was extensive, with smaller amounts of β-ZEL. When combined with its higher binding affinity, relative to ZEN and β-ZEL, α-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.