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

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 similar to 2 month-old female pigs using oral and intravenous dosing. The absolute bioavailability (AUC(oral)/AUC(IV)) of receptor-active ZEN aglycone was 1.8 +/- 0.80%, consistent with extensive pre-systemic Phase II conjugation. Reductive metabolism to alpha-zearalenol (alpha-ZEL) was extensive, with smaller amounts of beta-ZEL. When combined with its higher binding affinity, relative to ZEN and beta-ZEL, alpha-ZEL was the predominant contributor to total estrogen receptor ligand activity (similar to 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. Published by Elsevier Ltd.