The aim of this study was to characterize 27 feed additives marketed as mycotoxin binders and to screen them for their in vitro zearalenone (ZEN) adsorption. Firstly, 27 mycotoxin binders, commercially available in Belgium and The Netherlands, were selected and characterized. Characterization was comprised of X-ray diffraction (XRD) profiling of the mineral content and d-spacing, determination of the cation exchange capacity (CEC) and the exchangeable base cations, acidity, mineral fraction, relative humidity (RH) and swelling volume. Secondly, an in vitro screening experiment was performed to evaluate the adsorption of a single concentration of ZEN in a ZEN:binder ratio of 1:20,000. The free concentration of ZEN was measured after 4 h of incubation with each of the 27 mycotoxin binders at a pH of 2.5, 6.5 and 8.0. A significant correlation between the free concentration of ZEN and both the d-spacing and mineral fraction of the mycotoxin binders was seen at the three pH levels. A low free concentration of ZEN was demonstrated using binders containing mixed-layered smectites and binders containing humic acids.
The goal of this study was to determine the absolute oral bioavailability, (presystemic) hydrolysis and toxicokinetic characteristics of deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol in broiler chickens and pigs. Crossover animal trials were performed with intravenous and oral administration of deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol to broilers and pigs. Plasma concentrations were analyzed by using liquid chromatography-tandem mass spectrometry, and data were processed via a tailor-made compartmental toxicokinetic analysis. The results in broiler chickens showed that the absorbed fraction after oral deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol administration was 10.6, 18.2, and 42.2%, respectively. This fraction was completely hydrolyzed presystemically for 3-acetyldeoxynivalenol to deoxynivalenol and to a lesser extent (75.4%) for 15-acetyldeoxynivalenol. In pigs, the absorbed fractions were 100% for deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol, and both 3-acetyldeoxynivalenol and 15-acetyldeoxynivalenol were completely hydrolyzed presystemically. The disposition properties of 3-acetyldeoxynivalenol and 15-acetyldeoxynivalenol demonstrate their toxicological relevance and consequently the possible need to establish a tolerable daily intake.
Fusarium fungi frequently infest crops in temperate regions such as Western Europe and North America. They can produce a wide range of mycotoxins, including several extensively studied compounds such as trichothecenes, zearalenone and fumonisins. They are also capable of producing other less well-known mycotoxins like enniatins (ENNs) (enniatin (ENN) A, A1, B and B1) and beauvericin (BEA). ENNs are cyclic hexadepsipeptides consisting of alternating D-α-hydroxyisovaleric acids and L-methyl-amino acids. Over the last decade, ENNs were found to be common contaminants of grains, maize and other feedstuffs. Several in vitro toxicity studies elucidated their antibacterial, antifungal, antihelmintic, insecticidal and herbicidal potency. Also their cytotoxic effect on a variety of cell types was demonstrated previously. However, the biological activity of ENNs has only been tested in few in vivo studies, demonstrating low acute toxicity, and there are no cases of mycotoxicosis in humans and animals reported.The aim of present study was to reveal the toxicokinetic properties and absolute oral bioavailability of enniatin B1 in pigs. Five pigs were administered this Fusarium mycotoxin per os and intravenously in a two-way cross-over design. The toxicokinetic profile fitted a two-compartmental model. Enniatin B1 is rapidly absorbed after oral administration (T 1/2a = 0.15 h, T max = 0.24 h) and rapidly distributed and eliminated as well (T 1/2elα = 0.15 h; T 1/2elβ = 1.57 h). The absolute oral bioavailability is high (90.9%), indicating a clear systemic exposure. After intravenous administration, the mycotoxin is distributed and eliminated rapidly (T 1/2elα = 0.15 h; T 1/2elβ = 1.13 h), in accordance with oral administration.Future research should focus on elucidating the phase I and II metabolisation pathways of ENNs and the toxicity of these metabolites. Next, toxicokinetic studies of ENN B1, and other ENNs should be performed in other animal species to compare mycotoxin and species dependent differences in toxicity and sensitivity. Finally, the present study may serve as a model for humans, indicating that systemic exposure of ENNs after oral intake of contaminated food cannot be neglected.
The aim of present study was to reveal the toxicokinetic properties and absolute oral bioavailability of deoxynivalenol (DON) in turkey poults. Six turkey poults were administered this Fusarium mycotoxin per os and intravenously in a two-way cross-over design. Based on non-compartmental analysis, DON was absorbed rapidly (Tmax = 0.57 h) but incomplete, as the oral bioavailability was only 20.9%. Deoxynivalenol was rapidly eliminated as well, both after oral (T1/2elimination PO = 0.86 h) as well as intravenous (T1/2elimination IV = 0.62 h) administration. Furthermore, semi-quantitative analysis using high-resolution mass spectrometry revealed that DON-3α-sulfate is the major metabolite of DON in turkeys after intravenous as well as oral administration, with DON-3α-sulfate/DON ratios between 1.3-12.6 and 32.4-140.8 after intravenous and oral administration, respectively. Glucuronidation of DON to DON-3α-glucuronide is a minor pathway in turkey poults, with DON-3α-glucuronide/DON ratios between 0.009-0.065 and 0.020-0.481 after intravenous and oral administration, respectively. Only trace amounts of other metabolites were found including 10-DON-sulfonate, de-epoxydeoxynivalenol and 10-de-epoxydeoxynivalenol-sulfonate. In addition, a similar two-way cross-over study was performed in three broiler chickens, in order to compare the biotransformation of DON in both poultry species. High-resolution mass spectrometry revealed that DON-3α-sulfate was the major metabolite of DON in broiler chickens as well, with DON-3α-sulfate/DON ratios between 243-453 and 1365-29624 after intravenous and oral administration, respectively. These ratios indicate that broiler chickens metabolize DON even more extensively to the sulfate conjugate compared to turkey poults. Only trace amounts of other metabolites were detected in broiler chickens. In conclusion it can be stated that the toxicokinetic behavior of DON in broiler chickens and turkey poults is comparable (low absolute oral bioavailability, rapid absorption and elimination, extensive biotransformation to DON-3α-sulfate), however, relative differences in DON-3α-sulfate/DON ratios exist between both species which might explain the hypothesized difference in sensitivity of both poultry species to DON
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