Investigation of age-related differences in toxicokinetic processes of deoxynivalenol and deoxynivalenol-3-glucoside in weaned piglets.
Deoxynivalenol
Deoxynivalenol-3-glucoside
Pig
Plasma protein binding
Toxicokinetics
Weaning
Journal
Archives of toxicology
ISSN: 1432-0738
Titre abrégé: Arch Toxicol
Pays: Germany
ID NLM: 0417615
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
20
08
2019
accepted:
04
12
2019
pubmed:
14
12
2019
medline:
24
2
2021
entrez:
14
12
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31834428
doi: 10.1007/s00204-019-02644-x
pii: 10.1007/s00204-019-02644-x
doi:
Substances chimiques
Blood Proteins
0
Glucosides
0
Trichothecenes
0
deoxynivalenol-3-glucoside
0
deoxynivalenol
JT37HYP23V
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
417-425Subventions
Organisme : H2020 Food
ID : H2020-MYCOKEY-GA 678781
Pays : International
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