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

@article{Mukherjee2014PhysiologicallyBasedTM,
  title={Physiologically-Based Toxicokinetic Modeling of Zearalenone and Its Metabolites: Application to the Jersey Girl Study},
  author={Dwaipayan Mukherjee and Steven G. Royce and Jocelyn A. Alexander and Brian T Buckley and Sastry S. Isukapalli and Elisa V. Bandera and Helmut Zarbl and Panos G. Georgopoulos},
  journal={PLoS ONE},
  year={2014},
  volume={9}
}
Zearalenone (ZEA), a fungal mycotoxin, and its metabolite zeranol (ZAL) are known estrogen agonists in mammals, and are found as contaminants in food. Zeranol, which is more potent than ZEA and comparable in potency to estradiol, is also added as a growth additive in beef in the US and Canada. This article presents the development and application of a Physiologically-Based Toxicokinetic (PBTK) model for ZEA and ZAL and their primary metabolites, zearalenol, zearalanone, and their conjugated… 
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References

SHOWING 1-10 OF 63 REFERENCES
Metabolism and transfer of the mycotoxin zearalenone in human intestinal Caco-2 cells.
Risk assessment of the mycotoxin zearalenone.
Genotoxicity and inactivation of catechol metabolites of the mycotoxin zearalenone
TLDR
The catechol metabolites of the mycoestrogen ZEN and its reductive metabolite α-ZEL exhibit a DNA-damaging potential comparable to that of the catechl metabolites of E1 and E2, but are much poorer substrates for inactivation by human COMT.
Bioactivation of zearalenone by porcine hepatic biotransformation.
TLDR
The bioactivation of ZEA into the more active alpha-zearalenol seems to provide a possible explanation for the observed high sensitivity of pigs towards feeding-stuffs contaminated with the mycotoxin.
Physiologically Based Pharmacokinetics of Zearalenone
  • B. Shin, S. Hong, S. Yoo
  • Biology, Medicine
    Journal of toxicology and environmental health. Part A
  • 2009
TLDR
The developed physiologically based pharmacokinetic models for zearalenone following intravenous (iv) and oral (po) dosing in rats adequately described the pharmacokinetics in rats and may be useful in predicting human blood and tissue concentrations for zEARalen one under different po exposure conditions.
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