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Investigation of age-related differences in toxicokinetic processes of deoxynivalenol and deoxynivalenol-3-glucoside in weaned piglets

Abstract

Age-related differences in toxicokinetic processes of deoxynivalenol (DON) and deoxynivalenol-3-glucoside (DON3G) were studied. DON3G [55.7 µg/kg bodyweight (BW)] and an equimolar dose of DON (36 µg/kg BW) were administered to weaned piglets (4 weeks old) by single intravenous and oral administration in a double two-way cross-over design. Systemic and portal blood was sampled at different time points pre- and post-administration and plasma concentrations of DON, DON3G and their metabolites were quantified using validated liquid chromatography-tandem mass spectrometry (LC–MS/MS) and liquid chromatography–high-resolution mass spectrometry (LC–HRMS) methods. Data were processed using tailor-made compartmental toxicokinetic (TK) models to accurately estimate TK parameters. Results were statistically compared to data obtained in a previous study on 11-week-old pigs using identical experimental conditions. Significant age-related differences in intestinal and systemic exposure to both DON and DON3G were noted. Most remarkably, a significant difference was found for the absorbed fraction of DON3G, after presystemic hydrolysis to DON, in weaned piglets compared to 11-week-old piglets (83% vs 16%, respectively), assumed to be mainly attributed to the higher intestinal permeability of weaned piglets. Other differences in TK parameters could be assigned to a higher water/fat body ratio and longer gastrointestinal transit time of weaned piglets. Results may further refine current risk assessment concerning DON and DON3G in animals. Additionally, since piglets possibly serve as a human paediatric surrogate model, results may be extrapolated to human infants.

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Acknowledgements

The authors are grateful towards Prof. Adams (Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna) for the synthesis of the DON3G standard, used for animal and analytical experiments. The financial support from the European Union’s Horizon 2020 research and innovation programme under grant agreement H2020-MYCOKEY-GA 678781 is gratefully acknowledged.

Funding

This work was supported by Horizon 2020 (H2020-MYCOKEY-GA 678781).

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Correspondence to Siska Croubels.

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All applicable international, national and institutional guidelines for the care and use of animals were followed (EU 2010; KB 2013).

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Catteuw, A., Devreese, M., De Baere, S. et al. Investigation of age-related differences in toxicokinetic processes of deoxynivalenol and deoxynivalenol-3-glucoside in weaned piglets. Arch Toxicol (2019). https://doi.org/10.1007/s00204-019-02644-x

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Keywords

  • Deoxynivalenol
  • Deoxynivalenol-3-glucoside
  • Toxicokinetics
  • Pig
  • Weaning
  • Plasma protein binding