Physiologically-Based Toxicokinetic Modeling of Zearalenone and Its Metabolites: Application to the Jersey Girl Study

摘要: Zearalenone (ZEA), a fungal mycotoxin, and its metabolite zeranol (ZAL) are known estrogen agonists in mammals, found as contaminants food. Zeranol, which is more potent than ZEA comparable potency to estradiol, also added growth additive beef the US Canada. This article presents development application of Physiologically-Based Toxicokinetic (PBTK) model for ZAL their primary metabolites, zearalenol, zearalanone, conjugated glucuronides, rats human subjects. The PBTK modeling study explicitly simulates critical metabolic pathways gastrointestinal hepatic systems. Metabolic events such dehydrogenation glucuronidation chemicals, have direct effects on accumulation elimination toxic compounds, been quantified. considers urinary fecal excretion biliary recirculation compares predicted biomarkers blood, concentrations with published vivo measurements Additionally, toxicokinetic has coupled novel probabilistic dietary exposure applied Jersey Girl Study (JGS), involved measurement mycoestrogens biomarkers, cohort young girls New Jersey, USA. A characterization population conducted compared considering inter-individual physiological variability. from JGS fall within high low distributions biomarker values corresponding estimates calculated by system. work described here first kind present comprehensive framework developing potential exposures mycotoxins linking them biologically relevant doses measurements, including systematic uncertainties dose estimation vulnerable population.