Objective:

To develop a physiologically based kinetic (PBK) model predicting tissue concentrations of alternariol (AOH) and alternariol monomethyl ether (AME) in humans after oral intake, addressing a gap in understanding their exposure.

Approach:

• Model Development: A rodent model for AOH was developed and evaluated, followed by the creation of a human PBK framework through cross-species extrapolation, which was then extended to AME.
• Parameter Acquisition: Physiological, physicochemical, and kinetic parameters were sourced from literature or derived from quantitative structure–activity relationship (QSAR) predictions.
• In Vitro Studies: In vitro incubations were conducted to gather data on UGT-mediated glucuronidation kinetics of AOH and AME.
• Data Translation: The PBK models were used to translate known exposure data into predicted unbound concentrations in blood and target tissues.

Key Findings:

• AOH and AME are prevalent mycotoxins.
• The developed PBK model allows for the prediction of internal concentrations of AOH and AME in humans.
• Predicted tissue concentrations were compared with in vitro points-of-departure (PoDs) for relevant endpoints.

Interpretation:

The study provides a quantitative understanding of the bioactivity of AOH and AME.

Limitations:

• The model relies on existing data, which may not fully capture all exposure scenarios.
• Limited in vivo data for AOH and AME may affect the accuracy of predictions.

Conclusion:

The PBK modeling approach offers a framework for assessing human exposure to AOH and AME.