Croubels, Siska

De Saeger, Sarah

Devreese, Mathias

Huybrechts, B

Meerpoel, Celine

Tangni, E

Vidal Corominas, Arnau

English

Ghent University Academic Bibliography

INCIDENCE OF CITRININ IN THE BELGIAN FEED CHAIN AND ITSTOXICOKINETIC PROFILE IN BROILER CHICKENSC. MEERPOEL1,2, A. VIDAL2, B. HUYBRECHTS3, E. TANGNI3, S. DE SAEGER2, M. DEVREESE1 AND S. CROUBELS11 Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium2 Department of Bioanalysis, Centre of Excellence in Mycotoxicology and Public Health, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium 3 Chemical and Physical Health Risks, Organic Contaminants and Additives, Sciensano, Tervuren, Belgium* Corresponding author: Celine.Meerpoel@UGent.be A scientific opinion on CITRININ (CIT) published by EFSA1 emphasized that- additional quantitative occurrence and toxicity data is needed;- the impact of uncertainties on the risk assessment is large;- more data regarding the toxicity and the occurrence of CIT in food and feed are needed to enablerefinement. In Belgium, a risk assessment will be performed in order to set legal limits for this toxin, by usingcollected occurrence and toxicity data of CIT.INTRODUCTION OBJECTIVESCONCLUSIONS AND FURTHER RESEARCHMATERIALS AND METHODSFeed Toxin % Positive samplesAverage concentration* (µg/kg)Max concentration (µg/kg)Chicken (n = 38)CIT 45% 1.95 ± 0.46 3.9 ± 0.92Pig (n = 52)CIT 51% 1.58 ± 0.37 3.70 ± 0.87 Table 2: Occurrence of CIT in Belgian chicken and pig feed. Concentrations are shown with respect to their measurementuncertainty. *Of samples above LOQ (1 µg/kg)Data analysisQuEChERSextraction methodXevo TQ-S mass spectrometeroperated in ESI-RESULTSACN precipitation Filtration (OstroTM)Method validation CIT/HO-CIT in feed and chicken plasmaFEED CHICKEN PLASMACIT CIT HO-CITRange 1 – 250 µg/kg 0.1 – 100 ng/mL 0.1 – 100 ng/mLApparent recovery 80-107% 80-107% 80-110%RSDR <5 % <20 % <20 %LOD 0.5 µg/kg 0.05 ng/mL 0.05 ng/mLLOQ 1 µg/kg 0.1 ng/mL 0.1 ng/mLTable 1: Method performance parameters of the developed LC-MS/MS method for analysis of CIT/HO-CIT in animal feed and chicken plasma.Occurrence CIT in FEEDPreliminary results toxicokinetic profile CIT in chicken plasmaCollection of samplesFEEDA total of 90 feed samples (broiler chicken and pig feed) were obtained from different Belgian feedproducing companies from March 2017 until June 2017.CHICKEN PLASMAA dose of 0.25 mg/kg body weight of CIT (in physiological saline) was administered intravenously to 1 broilerchicken (Ross 308, 4 weeks old, ♂). Blood (200 µL, leg vein) was collected at 0, 0.08, 0.16, 0.33, 0.66, 0.75, 1,2, 3, 4, 6, 24, 48 and 72 h after administration.The trial was approved by the Ethical Committee of the Faculties of Bioscience Engineering and VeterinaryMedicine from Ghent University (case no. EC 2017/105).Sample pretreatmentToxicokinetic study: Toxicokinetic parameters?Steady-state study: Carry-over to edible tissues? (Fig. 3)Post-mortem evaluation: Organ damage?MetID (HRMS): CIT phase I and phase II metabolites  CIT frequently occurs in Belgian feed, although in low concentration levels Limited data is available concerning its toxicity and toxicokinetics. Hence, further research is needed.CITCITn = 32CIT?n = 16CIT?CIT?Fig. 3: Presentation of experimental set-up for carry-over studyFig 1: Overview sample preparation for extraction of CIT in feed and chicken plasmaContactceline.meerpoel@ugent.bewww.vetftb.ugent.beUniversiteit Gent@ugentGhent UniversityFig 2. Plasma concentration−time profile of CIT and HO-CIT after single intravenous administration of 0.25 mg CIT /kg body weight to broiler chicken (n=1 ♂). The inserts are the chemical structures of (A) CIT and (B) HO-CIT.11010010000 10 20 30 40 50 60 70 80Plasma concentration (ng/mL)Time post administration (h)CITHO-CITABCompared to Devreese et al1. (2018), the preliminary elimination rate constant (Kel) of CIT in broiler chickens is inline with the Kel of ochratoxin A after IV administration of 0.25 mg/kg body weight (Table 3). More data from atoxicokinetic study with a sufficient number of animals (n = 8) should confirm this.C0(ng/L) AUC0-72h(h*ng/L) Kel(1/h) T1/2el(h) Vd(L/kg) Cl (L/h/kg)   OTA 910.52 ± 627.31 335.57 ± 79.30 0.045 ± 0.021 23.95 ± 15.27 19.85 ± 11.74 0.61 ± 0.12CIT 434.69 1920.80 0.04 17.68 3.32 0.13Table 3. Comparison of toxicokinetic parameters of CIT and OTA1 after intravenous administration of 0,25 mg/kg body weight tobroiler chickens (CIT: n = 1♂/OTA: n = 4 ♀/ 4♂),CIT?1 M. Devreese, S. Croubels, S. De Baere, R. Gehring, G. Antonissen, Comparative Toxicokinetics and Plasma Protein Binding of Ochratoxin A in Four Avian Species, J. Agric. Food Chem. 66 (2018) 2129–2135.. To collect occurrence data of CIT in feed in Belgium- an LC-MS/MS method was developed for analysis of CIT in feed (pig and chicken);- this validated method was applied on 90 Belgian feedstuffs. To collect toxicokinetic data of CIT and its metabolite dihydrocitrinone (HO-CIT) in broiler chickens- an LC-MS/MS method was developed for analysis of CIT and HO-CIT in chicken plasma;- a pilot toxicokinetic study was performed on 1 broiler chicken.The research was funded by the Belgian Federal Public Service of Health, Food Chain Safety and Environment through the contract RT 16/6308 CITRIRISK.CIT was detected in about half of the sampled feedstuffs (Table 2).

Incidence of citrinin in the Belgian feed chain and its toxicokinetic profile in broiler chickens

https://biblio.ugent.be/publication/8569762/file/8569764.pdf

Incidence of citrinin in the Belgian feed chain and its toxicokinetic profile in broiler chickens

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