Abstract
Deoxynivalenol (DON) is the most widespread mycotoxin in food and feedstuffs, posing a persistent health threat to humans and farm animals. The susceptibilities of DON vary significantly among animals, following the order of pigs, mice/rats and poultry from the most to least susceptible. However, no study comprehensively disentangles factors shaping species-specific sensitivity. In this review, the toxicokinetics and metabolism of DON are summarized in animals and humans. Generally, DON is fast-absorbed and widely distributed in multiple organs. DON is first enriched in the plasma, liver and kidney and subsequently accumulates in the intestine. There are also key variations among animals. Pigs and humans are highly sensitive to DON, and they have similar absorption rates (1 h < tmax < 4 h), high bioavailability (> 55%) and long clearance time (2 h < t1/2 < 4 h). Also, both species lack detoxification microorganisms and mainly depend on liver glucuronidation and urine excretion. Mice and rats have similar toxicokinetics (tmax < 0.5 h, t1/2 < 1 h). However, a higher proportion of DON is excreted by feces as DOM-1 in rats than in mice, suggesting an important role of gut microbiota in rats. Poultry is least sensitive to DON due to their fast absorption rate (tmax < 1 h), low oral bioavailability (5–30%), broadly available detoxification gut microorganisms and short clearance time (t1/2 < 1 h). Aquatic animals have significantly slower plasma clearance of DON than land animals. Overall, studies on toxicokinetics provide valuable information for risk assessment, prevention and control of DON contamination.
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Abbreviations
- DON:
-
Deoxynivalenol
- DOM-1:
-
Deepoxy-deoxynivalenol
- DON-3GlcA:
-
Deoxynivalenol-3-glucuronide
- DON-15GlcA:
-
Deoxynivalenol-15-glucuronide
- 3-ADON:
-
3-Acetyl-deoxynivalenol
- 15-ADON:
-
15-Acetyl-deoxynivalenol
- DON-3G:
-
Deoxynivalenol-3-glucoside
- DON-3S:
-
Deoxynivalenol-3-sulfate
- DON-GSH:
-
Deoxynivalenol-glutathione
- 3H-DON:
-
Tritium-labeled deoxynivalenol
- 14C-DON:
-
14 C-labeled deoxynivalenol
- DOM-1:
-
Deepoxy-deoxynivalenol
- DOM-15GlcA:
-
Deepoxy-deoxynivalenol-15-glucuronide
- IC50:
-
The concentration of mycotoxin which exhibited 50% cell viability
- CLp :
-
Plasma clearance
- V d :
-
Volume of distribution
- t 1/2 :
-
Elimination half-life
- t max :
-
Time to maximal plasma concentration
- c max :
-
Maximal plasma concentration
- f :
-
Bioavailability
- AUC:
-
Area under the plasma concentration–time curve
- TDI:
-
Tolerable daily intake
- PMTDI:
-
Permissible tolerable daily intake
- PDI:
-
Probable daily intake
- IVIVE:
-
In vitro-to-in vivo extrapolation
- PO:
-
Oral
- IV:
-
Intravenous
- bw:
-
Body weight
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Acknowledgements
This work was supported by the Joint Fund of National Natural Science Foundation of China and Guangdong Province [U1901207], Laboratory of Lingnan Modern Agriculture Project [NZ2021016], National Natural Science Foundation of China (32102718, 32172770) and China Postdoctoral Science Foundation (grant numbers 2021M691081).
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Sun, Y., Jiang, J., Mu, P. et al. Toxicokinetics and metabolism of deoxynivalenol in animals and humans. Arch Toxicol 96, 2639–2654 (2022). https://doi.org/10.1007/s00204-022-03337-8
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DOI: https://doi.org/10.1007/s00204-022-03337-8