Toxicokinetics of Hydrolyzed Fumonisin B1 after Single Oral or Intravenous Bolus to Broiler Chickens Fed a Control or a Fumonisins-Contaminated Diet

Gunther Antonissen,Dian Schatzmayr,Siska Croubels,Barbara Novak,Siegrid De Baere,Mathias Devreese,Danica Den Hollander

doi:10.3390/toxins12060413

Abstract

The toxicokinetics (TK) of hydrolyzed fumonisin B1 (HFB1) were evaluated in 16 broiler chickens after being fed either a control or a fumonisins-contaminated diet (10.8 mg fumonisin B1, 3.3 mg B2 and 1.5 mg B3/kg feed) for two weeks, followed by a single oral (PO) or intravenous (IV) dose of 1.25 mg/kg bodyweight (BW) of HFB1. Fumonisin B1 (FB1), its partially hydrolyzed metabolites pHFB1a and pHFB1b, and fully hydrolyzed metabolite HFB1, were determined in chicken plasma using a validated ultra-performance liquid chromatography–tandem mass spectrometry method. None of the broiler chicken showed clinical symptoms of fumonisins (FBs) or HFB1 toxicity during the trial, nor was an aberration in body weight observed between the animals fed the FBs-contaminated diet and those fed the control diet. HFB1 was shown to follow a two-compartmental pharmacokinetic model with first order elimination in broiler chickens after IV administration. Toxicokinetic parameters of HFB1 demonstrated a total body clearance of 16.39 L/kg·h and an intercompartmental flow of 8.34 L/kg·h. Low levels of FB1 and traces of pHFB1b were found in plasma of chickens fed the FBs-contaminated diet. Due to plasma concentrations being under the limit of quantification (LOQ) after oral administration of HFB1, no toxicokinetic modelling could be performed in broiler chickens after oral administration of HFB1. Moreover, no phase II metabolites, nor N-acyl-metabolites of HFB1 could be detected in this study.

Highlights

Fumonisins (FBs) are secondary fungal metabolites of Fusarium verticillioides, F. proliferatum or other Fusarium species, that resemble each other structurally [1,2]
FB2 and 3 differ structurally from Fumonisin B1 (FB1) in the in the number and position of hydroxyl groups, since a free hydroxyl group is lacking on either number and position of hydroxyl groups, since a free hydroxyl group is lacking on either the C-10 or the C-10 or the C-5
hydrolyzed fumonisin B1 (HFB1) is generally known to be less toxic than its parent toxin FB1 [26,27], and poultry species are known to be able to tolerate high doses of FB1, especially regarding performance response, with no effect on growth of broiler chickens up to 75–100 mg FB1 /kg feed [15]

Summary

Introduction

Fumonisins (FBs) are secondary fungal metabolites of Fusarium verticillioides, F. proliferatum or other Fusarium species, that resemble each other structurally [1,2]. Toxins 2020, 12, 413; doi:10.3390/toxins12060413 www.mdpi.com/journal/toxins prevalent and toxic analogue, toxicological assessment. FB1 isofa and toxic analogue, toxicological assessment of FBs hasofmostly been donebeen for FB 1. Diester of propane-1,2,3-tricarboxylic acid (TCA), which has a long aminopolyol side-chain, namely propane-1,2,3-tricarboxylic acid (TCA), which has a long aminopolyol side-chain, namely 2-amino2-amino-12,16-dimethyl-3,5,10,14,15-pentahydroxyeicosane [3].FB FB from 2 and FB. FB2 and 3 differ structurally from FB1 in the in the number and position of hydroxyl groups, since a free hydroxyl group is lacking on either number and position of hydroxyl groups, since a free hydroxyl group is lacking on either the C-10 or the C-10 or the C-5

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