Metabolism and pharmacokinetics of zearalenone following oral and intravenous administration in juvenile female pigs.
Food Chem Toxicol
; 106(Pt A): 193-201, 2017 Aug.
Article
en En
| MEDLINE
| ID: mdl-28552786
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 â¼2 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 ß-ZEL. When combined with its higher binding affinity, relative to ZEN and ß-ZEL, α-ZEL was the predominant contributor to total estrogen receptor ligand activity (â¼90%) 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Zearalenona
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Food Chem Toxicol
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos