T-2 toxin-3α-glucoside in broiler chickens : toxicokinetics, absolute oral bioavailability, and in vivo hydrolysis

Due to the lack of information on bioavailability and toxicity of Modified mycotoxins, current risk assessment on these modified forms assumes an identical toxicity of the modified form to their respective unmodified counterparts, Crossover animal trials were performed with intravenous and oral administration of T-2 toxin (T-2) and T-2 toxin-3 alpha-glucoside (T2-G) to broiler thickens. Plasma concentrations of T2-G, T-2, and main phase I metabolites were quantified Using a validated chromatography-tandem mass spectrometry method with a limit of quantitation for all compounds of 0.1 ng/mL. Resulting plasma concentration time profiles were processed via two-compartmental toxicokinetic models. No T-2 triol and only traces of HT-2 were detected in the plasma samples after both intravenous and oral administration. The results, indicate that T-2, has a low absolute oral bioavailability of 2.17 +/- 1.80%. For T2-G, an absorbed fraction of the dose and absolute oral bioavailability of 10.4 +/- 8.7% and 10.1 +/- 8.5% were observed, respectively. This slight difference is caused by a minimal (and neglectable) presystemic hydrolysis of T2-G to T-2, that is, 3.49 +/- 1.19%. Although low, the absorbed fraction of T2-G is 5 times higher than that of T-2. These differences in toxicokinetics parameters between T-2 and T2-G clearly indicate the flaw in assuming equal bioavailability and/or toxicity of modified and free mycotoxins in current risk assessments

Characterization of 27 mycotoxin detoxifiers and the relation with in vitro zearalenone binding

Addition of mycotoxin detoxifiers to feed is a common practice to counteract the deleterious effects of mycotoxins on animal health. Although a variety of this kind of feed additives is available on the market, little is known about their detailed composition and physico-chemical properties. This lack of knowledge might pose some difficulties for researchers and users to compare and evaluate the efficacy and safety of these additives. The present study describes the characterization of 27 commercially available mycotoxin detoxifiers collected from various sources in Flanders and The Netherlands. Characterization comprised XRD-profiling of the mineral content, determination of the cation exchange capacity and exchangeable cations, acidity, mineral fraction, humidity and swelling volume. The XRD- and mineral fraction data were analysed with principal component analysis and explorative cluster analysis which enabled the identification of three distinct groups: smectite based (n=19), non-smectite based (n=5) and organic based detoxifiers (n=4). In a second experiment, an in vitro zearalenone binding test was conducted using phosphate buffered saline at pH 2.5, 6.5 and 8.0. The zearalenone binding of the smectite based group was related to the physico-chemical properties using a multivariate linear regression model. The binding in the non-smectite based and organic based groups was analysed using a one-way ANOVA. A large variability in binding properties was present, especially in the smectite containing group. Additives with smectite-containing mixed-layered minerals and additives containing humic acids expressed the highest binding which amounted to over 90%. The retained multivariate linear model included exchangeable potassium (p≤0.05), moist content (p≤0.05) and mineral fraction (0.05≤p≤0.1), indicating a statistical relation of these parameters with the in vitro zearalenone binding

The impact of deoxynivalenol on pigeon health : occurrence in feed, toxicokinetics and interaction with salmonellosis

Seed-based pigeon diets could be expected to result in exposure of pigeons to mycotoxins such as deoxynivalenol (DON). Ingestion of low to moderate contamination levels of DON may impair intestinal health, immune function and/or pathogen fitness, resulting in altered host-pathogen interactions and thus different outcome of infections. Here we demonstrate that DON was one of the most frequently detected mycotoxins in seed-based racing pigeons feed, contaminating 5 out of 10 samples (range 177-1,466 mu g/kg). Subsequently, a toxicokinetic analysis revealed a low absolute oral bioavailability (F) of DON in pigeons (30.4%), which is comparable to other avian species. Furthermore, semi-quantitative analysis using high-resolution mass spectrometry revealed that DON-3 alpha-sulphate is the major metabolite of DON in pigeons after intravenous as well as oral administration. Following ingestion of DON contaminated feed, the intestinal epithelial cells are exposed to significant DON concentrations which eventually may affect intestinal translocation and colonization of bacteria. Feeding pigeons a DON contaminated diet resulted in an increased percentage of pigeons shedding Salmonella compared to birds fed control diet, 87 +/- 17% versus 74 +/- 13%, respectively. However, no impact of DON was observed on the Salmonella induced disease signs, organ lesions, faecal and organ Salmonella counts. The presented risk assessment indicates that pigeons are frequently exposed to mycotoxins such as DON, which can affect the outcome of a Salmonella infection. The increasing number of pigeons shedding Salmonella suggests that DON can promote the spread of the bacterium within pigeon populations

In vivo contribution of deoxynivalenol-3-β-D-glucoside to deoxynivalenol exposure in broiler chickens and pigs: oral bioavailability, hydrolysis and toxicokinetics

Crossover animal trials were performed with intravenous and oral administration of deoxynivalenol-3-β-D-glucoside (DON3G) and deoxynivalenol (DON) to broiler chickens and pigs. Systemic plasma concentrations of DON, DON3G and de-epoxy-DON were quantified using liquid chromatography-tandem mass spectrometry. Liquid chromatography coupled to high-resolution mass spectrometry was used to unravel phase II metabolism of DON. Additionally for pigs, portal plasma was analysed to study presystemic hydrolysis and metabolism. Data were processed via tailor-made compartmental toxicokinetic models. The results in broiler chickens indicate that DON3G is not hydrolysed to DON in vivo. Furthermore, the absolute oral bioavailability of DON3G in broiler chickens was low (3.79 ± 2.68 %) and comparable to that of DON (5.56 ± 2.05 %). After PO DON3G administration to pigs, only DON was detected in plasma, indicating a complete presystemic hydrolysis of the absorbed fraction of DON3G. However, the absorbed fraction of DON3G, recovered as DON, was approximately 5 times lower than after PO DON administration, 16.1 ± 5.4 compared with 81.3 ± 17.4 %. Analysis of phase II metabolites revealed that biotransformation of DON and DON3G in pigs mainly consists of glucuronidation, whereas in chickens predominantly conjugation with sulphate occurred. The extent of phase II metabolism is notably higher for chickens than for pigs, which might explain the differences in sensitivity of these species to DON. Although in vitro studies demonstrate a decreased toxicity of DON3G compared with DON, the species-dependent toxicokinetic data and in vivo hydrolysis to DON illustrate the toxicological relevance and consequently the need for further research to establish a tolerable daily intake

Development and validation of an UPLC-MS/MS method for the determination of ionophoric and synthetic coccidiostats in vegetables

In poultry farming, anticoccidial drugs are widely used as feed additives for the prevention and treatment of coccidiosis. Because coccidiostats and veterinary medicines, in general, are often poorly absorbed, manure from treated animals may contain high concentrations of these compounds. Experimental studies have shown that the uptake of veterinary medicines by plants from soil containing contaminated manure may occur. This leads to several questions regarding the impact on the environment, resistance problems, and public health and allergy issues. This work describes the development of a quantification method for coccidiostats in vegetables. Vegetables were spiked at 100 mu g kg(-1) (dry weight) with coccidiostats (monensin, narasin, lasalocid A, salinomycin, diclazuril, and nicarbazin) in order to optimize the extraction and clean-up. Possible critical factors (e.g., extraction solvent) were statistically examined by linear regression with the use of Plackett-Burman and full factorial designs. Final extracts were analyzed with ultra-performance liquid chromatography tandem mass spectrometry operating in multiple-reaction monitoring mode. Both the synthetic and ionophoric coccidiostats could be determined in a single run with an analysis time of 5 min. The developed method was validated taking into account the requirements of the Commission Decision 2002/657/EC as a guideline. The method is regarded as applicable for its intended purposes with quantification limits between 0.30 and 2.98 mu g kg(-1). This method could be used to establish possible maximum residue limits for coccidiostats in vegetables, as already exist for eggs, meat, and milk