Toxicokinetics of hydrolyzed fumonisin B1 after single oral or intravenous bolus to broiler chickens fed a control or a fumonisins-contaminated diet

The toxicokinetics (TK) of hydrolyzed fumonisin B-1(HFB1) were evaluated in 16 broiler chickens after being fed either a control or a fumonisins-contaminated diet (10.8 mg fumonisin B-1, 3.3 mg B(2)and 1.5 mg B-3/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 B-1(FB1), its partially hydrolyzed metabolites pHFB(1a)and pHFB(1b), 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 HFB(1)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. HFB(1)was shown to follow a two-compartmental pharmacokinetic model with first order elimination in broiler chickens after IV administration. Toxicokinetic parameters of HFB(1)demonstrated a total body clearance of 16.39 L/kg center dot h and an intercompartmental flow of 8.34 L/kg center dot h. Low levels of FB(1)and traces of pHFB(1b)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 HFB(1)could be detected in this study

Applied research note : biomonitoring of mycotoxins in blood serum and feed to assess exposure of broiler chickens

Because European maximum guidance values of mycotoxins are only available for feed, mycotoxin exposure in animals is mainly monitored by feed analysis. However, proper sample collection is needed to ensure reliable results because of uneven distributions and disproportional spread of mycotoxins in feed which can hamper the evaluation of mycotoxin exposure in animals. A cross-sectional study was performed on 40 randomly selected broiler farms in Belgium. During a farm visit at the animal's age of 28 d, a pooled feed sample at the beginning and the end of the feed line was collected. Feed samples were analyzed by a validated multimycotoxin LC-MS/MS method. Moreover, serum samples were collected from 10 randomly selected chickens per farm. Serum concentrations of mycotoxins and major in vivo phase I metabolites were analyzed quantitatively, whereas the presence of phase II metabolites was determined in a qualitative approach by an UPLC-HRMS method. Deoxynivalenol (DON) was the most frequently occurring mycotoxin, being present in 74% of the feed samples, with an average concentration of 270 +/- 171 mu g/kg and a maximum concentration of 751 mu g/kg in positive samples. Also the acetylated forms 3and 15-acetyldeoxynivalenol (3 and 15ADON) were present in half of the samples, however, at lower concentrations (8 +/- 3 mu g 3ADON and 10 +/- 7 mu g 15ADON/kg). Only in 17.5% of the farms, DON was detected in serum samples at a mean serum concentration and standard deviation (SD) of 11 +/- 19 ng/mL. The maximum serum concentration of 49 ng DON/ mL was detected in broilers which were fed a diet that was contaminated with 191 mu g DON/kg, whereas the maximum concentration of DON in feed was 751 mu g/kg. Besides, 3 and 15ADON were only detected in 10% of the serum samples (max. 1.3 ng/mL). Sulfate conjugates of DON were only detected in a few serum samples. Qualitative screening for phase II metabolites of other mycotoxins showed similar results. Overall, correlations between feed and serum concentrations of all mycotoxins were lacking (R-2 = 0.18 for DON)

Cytotoxic effects of alternariol, alternariol monomethyl-ether, and tenuazonic acid and their relevant combined mixtures on human enterocytes and hepatocytes

Alternariol (AOH), alternariol monomethyl-ether (AME), and tenuazonic acid (TeA) are major mycotoxins produced by fungi of the genus Alternaria and are common contaminants of food products such as fruits, vegetables, cereals and grains. Alternaria mycotoxins are known to cause relevant economic losses and to have a negative impact on human and animal health. EFSA stated in its scientific opinion that data on the toxicity of Alternaria mycotoxins in humans and livestock are generally lacking, precluding proper hazard characterization. This study aimed to fill some knowledge gaps by studying the in vitro cytotoxicity toward human intestinal epithelial cells (Caco-2) and hepatocytes (HepG2). Cytotoxic properties were assessed by flow cytometric analyses of remaining viable cells (i.e., propidium iodide negative) after mycotoxin exposure for 24-48 h versus solvent control. Treatment of cells with single doses of AOH, AME, and TeA resulted in a dose-dependent loss of cell viability for both cell lines. Half maximal effective concentrations (EC50) of the different mycotoxins were comparable for the two cell lines. On HepG2 cells, EC50 values varying between 8 and 16, 4 and 5, and 40 and 95 mu g/mL were calculated for AOH, AME, and TeA, respectively. On Caco-2 cells, EC50 values of 19 mu g/mL and varying between 6 and 23, and 60 and 90 mu g/mL were calculated for AOH, AME, and TeA, respectively. A general relative cytotoxicity ranking of about 1 = 1 >>> 3 was obtained for AOH, AME, and TeA, respectively. Treatment of both cell lines with combined binary and ternary mixtures of AOH, AME, and TeA in a 1:1:3 ratio, also showed a dose-dependent decrease in cell viability. For both cell lines, the binary combination of especially AME and TeA (1:3 ratio) but also of AOH and AME (1:1 ratio) significantly increased the cytotoxicity compared to the single compound toxicity, although mainly at the highest concentrations tested. The ternary combinations of AOH, AME, and TeA induced only a slight increase in cytotoxicity compared to the single mycotoxins, again at the highest concentrations tested