Prediction of deoxynivalenol toxicokinetics in humans by in vitro-to-in vivo extrapolation and allometric scaling of in vivo animal data

Archives of Toxicology
Christiane Kruse FæsteSilvio Uhlig

Abstract

Deoxynivalenol (DON) is the most prevalent mycotoxin in cereals worldwide. It can cause adverse health effects in humans and animals, and maximum levels in food and feed have been implemented by food authorities based on risk assessments derived from estimated intake levels. The lack of human toxicokinetic data such as absorption, distribution, and elimination characteristics hinders the direct calculation of DON plasma levels and exposure. In the present study, we have, therefore, used in vitro-to-in vivo extrapolation of depletion constants in hepatic microsomes from different species and allometric scaling of reported in vivo animal parameters to predict the plasma clearance [0.24 L/(h × kg)] and volume of distribution (1.24 L/kg) for DON in humans. In addition, we have performed a toxicokinetic study with oral and intravenous administration of DON in pigs to establish benchmark parameters for the in vitro extrapolation approach. The determined human toxicokinetic parameters were then used to calculate the bioavailability (50-90%), maximum concentration, and total exposure in plasma, and urinary concentrations under consideration of typical DON levels in grain-based food products. The results were compared to data from biomo...Continue Reading

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Citations

Jan 4, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Madelyn C HuangDori Germolec
Feb 1, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Wim SchelstraeteSiska Croubels
Apr 16, 2020·Ecotoxicology and Environmental Safety·Amritha JohnyChristiane Kruse Fæste
Jul 29, 2021·Chemical Research in Toxicology·Jessica Kay GwinnAlison Robertson
Dec 24, 2019·Chemical Research in Toxicology·Silvio UhligChristopher O Miles

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Methods Mentioned

BETA
Protein Assay
sedation
sulphotransferases

Software Mentioned

Phoenix 64 WinNonlin
Xcalibur
IVIVE
Google Scholar

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