Matrix-associated mycotoxins that bind with macromolecular components through covalent or non-covalent interactions easily occur in various cereals, cereal-based products, and cereal-based feedstuff. ...They are "masked" by macro-components, causing the underestimation of total exposure risk of mycotoxins. Most of the current reports focus on the free and modified mycotoxins, while the matrix-associated forms are ignored but still can exert toxic effects after ingestion. In this paper, current researches and future prospects of matrix-associated mycotoxins are reviewed. Especially, a focus is set on the transformation of matrix-associated mycotoxins with their free forms during metabolism and food processing. Enzymes, temperature and pH levels during food processing can induce the interconversion of matrix-associated mycotoxins with free mycotoxins. Furthermore, the analytical methods targeted on matrix-associated mycotoxins are discussed. Due to the lack of efficient methods releasing the mycotoxins from matrix, the standard analytical methods has not developed so far. Also, we further analyzed the challenges of matrix-associated mycotoxins about variety, occurrence, toxicity and transformation, exposure assessment, which contributes to establish preventive measures to control their hazards for consumers. Overall, this overview is significant for perfecting risk assessment, as well as developing effective prevention and control actions to matrix-associated mycotoxins.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
•A compilation of in vivo studies about Fusarium mycotoxins in the last decade was performed.•The main Fusarium mycotoxins studied were identified.•The in vivo assays were classified regarding the ...proposed objective.•Aspects such as animal species, doses, application routine, exposure time, and results obtained were analyzed.
This review summarizes the information regarding the in vivo studies of Fusarium mycotoxins in the last decade. The most common studies are classified as subacute toxicity, subchronic toxicity, acute toxicity, toxicokinetic studies and teratogenicity in order of importance. The most used animals in in vivo studies are pigs, rats, chickens and mice. Fumonisin B1, deoxynivalenol, zearalenone, nivalenol and T-2 toxin are the most studied fusarotoxins. Studies with combinations of mycotoxins are also frequent, deoxynivalenol generally being one of them. The predominant route of administration is oral, administered mostly in the form of naturally contaminated feed. Other administration routes also used are intraperitoneal, intravenous and subcutaneous. In vivo research on Fusarium mycotoxins has increased since 2010 highlighting the need for such studies in the field of food and feed safety.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Mycotoxin contamination of cereal grains causes well-recognized toxicities in animals and humans, but the fate of plant-bound masked mycotoxins in the gut is less well understood. Masked mycotoxins ...have been found to be stable under conditions prevailing in the small intestine but are rapidly hydrolyzed by fecal microbiota. This study aims to assess the hydrolysis of the masked mycotoxin deoxynivalenol-3-glucoside (DON3Glc) by the microbiota of different regions of the porcine intestinal tract. Intestinal digesta samples were collected from the jejunum, ileum, cecum, colon, and feces of 5 pigs and immediately frozen under anaerobic conditions. Sample slurries were prepared in M2 culture medium, spiked with DON3Glc or free deoxynivalenol (DON; 2 nmol/ml), and incubated anaerobically for up to 72 h. Mycotoxin concentrations were determined using liquid chromatography-tandem mass spectrometry, and the microbiota composition was determined using a quantitative PCR methodology. The jejunal microbiota hydrolyzed DON3Glc very slowly, while samples from the ileum, cecum, colon, and feces rapidly and efficiently hydrolyzed DON3Glc. No further metabolism of DON was observed in any sample. The microbial load and microbiota composition in the ileum were significantly different from those in the distal intestinal regions, whereas those in the cecum, colon and feces did not differ.
Results from this study clearly demonstrate that the masked mycotoxin DON3Glc is hydrolyzed efficiently in the distal small intestine and large intestine of pigs. Once DON is released, toxicity and absorption in the distal intestinal tract likely occur
This study further supports the need to include masked metabolites in mycotoxin risk assessments and regulatory actions for feed and food.
The genus Fusarium includes numerous toxigenic species that are pathogenic to plants or humans, and are able to colonize a wide range of environments on earth. The genus comprises around 70 ...well-known species, identified by using a polyphasic approach, and as many as 300 putative species, according to phylogenetic species concepts; many putative species do not yet have formal names. Fusarium is one of the most economically important fungal genera because of yield loss due to plant pathogenic activity; mycotoxin contamination of food and feed products which often render them unaccep for marketing; and health impacts to humans and livestock, due to consumption of mycotoxins. Among the most important mycotoxins produced by species of Fusarium are the trichothecenes and the fumonisins. Fumonisins cause fatal livestock diseases and are considered potentially carcinogenic mycotoxins for humans, while trichothecenes are potent inhibitors of protein synthesis. This chapter summarizes the main aspects of morphology, pathology, and toxigenicity of the main Fusarium species that colonize different agricultural crops and environments worldwide, and cause mycotoxin contamination of food and feed.
The development of liquid chromatography-mass spectrometry (LC-MS)/mass spectrometry (MS) methods for the simultaneous detection and quantification of a broad spectrum of mycotoxins has facilitated ...the screening of a larger number of samples for contamination with a wide array of less well-known "emerging" mycotoxins and other metabolites. In this study, 83 samples of feed and feed raw materials were analysed. All of them were found to contain seven to 69 metabolites. The total number of detected metabolites amounts to 139. Fusarium mycotoxins were most common, but a number of Alternaria toxins also occurred very often. Furthermore, two so-called masked mycotoxins (i.e., mycotoxin conjugates), namely deoxynivalenol-3-glucoside (75% positives) and zearalenone-4-sulfate (49% positives), were frequently detected. Although the observed median concentrations of the individual analytes were generally in the low μg/kg range, evaluating the toxicological potential of a given sample is difficult. Toxicity data on less well-known mycotoxins and other detected metabolites are notoriously scarce, as an overview on the available information on the most commonly detected metabolites shows. Besides, the possible synergistic effects of co-occurring substances have to be considered.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Emerging
and
mycotoxins gain more and more interest due to their frequent contamination of food and feed, although in vivo toxicity and toxicokinetic data are limited. Whereas the
mycotoxins ...beauvericin, moniliformin and enniatins particularly contaminate grain and grain-based products,
mycotoxins are also detected in fruits, vegetables and wines. Although contamination levels are usually low (µg/kg range), higher contamination levels of enniatins and tenuazonic acid may occasionally occur. In vitro studies suggest genotoxic effects of enniatins A, A1 and B1, beauvericin, moniliformin, alternariol, alternariol monomethyl ether, altertoxins and stemphyltoxin-III. Furthermore, in vitro studies suggest immunomodulating effects of most emerging toxins and a reproductive health hazard of alternariol, beauvericin and enniatin B. More in vivo toxicity data on the individual and combined effects of these contaminants on reproductive and immune system in both humans and animals is needed to update the risk evaluation by the European Food Safety Authority. Taking into account new occurrence data for tenuazonic acid, the complete oral bioavailability, the low total body clearance in pigs and broiler chickens and the limited toxicity data, a health risk cannot be completely excluded. Besides, some less known
toxins, especially the genotoxic altertoxins and stemphyltoxin III, should be incorporated in risk evaluation as well.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Mycotoxins are secondary metabolites of fungi poisonous for humans or animals which can be found on a great variety of food and feed commodities. Food is not necessarily safe just because the ...presence of well-known mycotoxins has been ruled out, as they might still be there in disguise. Mycotoxins may also occur in conjugated form, either soluble (masked mycotoxins) or incorporated into/associated with/attached to macromolecules (bound mycotoxins). These conjugated mycotoxins can emerge after metabolization by living plants, fungi and mammals or after food processing. Awareness of such altered forms of mycotoxins is increasing, but reliable analytical methods, measurement standards and occurrence and toxicity data are still lacking. In this paper currently known conjugated mycotoxins, their formation and determination are reviewed. For the latter, liquid chromatography-(tandem) mass spectrometry or ELISA methods are employed with or without conversion to the parent mycotoxins. Sample preparation to transform the bound forms into soluble forms can involve enzymatic or acidic/alkaline treatment. Especially mycotoxins which are in contact with living plants in the field are prone to be metabolized. This transformation process is not only important regarding food safety but also for the resistance of plants towards fungal-induced diseases, such as Fusarium head blight of wheat.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Mycotoxins are toxic, secondary metabolites produced by fungi. They occur in a wide variety of food and feed commodities, and are of major public health concern because they are the most hazardous of ...all food and feed contaminants in terms of chronic toxicity. In the past decades, it has become clear that in mycotoxin-contaminated commodities, many structurally related compounds generated by plant metabolism, fungi or food processing coexist with their free mycotoxins, defined as modified mycotoxins. These modified xenobiotics might endanger animal and human health as they are possibly hydrolysed into their free toxins in the digestive tract of mammals, and may consequently contribute to an unexpected high toxicity. As modified toxins represent an emerging issue, it is not a surprise that for most toxicological tests data are scarce to non-existent. Therefore, there is a need to elucidate the disposition and kinetics of both free and modified mycotoxins in mammals to correctly interpret occurrence data and biomonitoring results. This review emphasizes the current knowledge on the metabolism of modified mycotoxins using in vitro and in vivo models.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A sensitive and reliable multi-mycotoxin-based method was developed to identify and quantify several carcinogenic mycotoxins in human blood and urine, as well as edible animal tissues, including ...muscle and liver tissue from swine and chickens, using liquid chromatography–tandem mass spectrometry (LC–MS/MS). For the toxicokinetic studies with individual mycotoxins, highly sensitive analyte-specific LC–MS/MS methods were developed for rat plasma and urine. Sample purification consisted of a rapid ‘dilute and shoot’ approach in urine samples, a simple ‘dilute, evaporate and shoot’ approach in plasma samples and a ‘QuEChERS’ procedure in edible animal tissues. The multi-mycotoxin and analyte-specific methods were validated in-house: The limits of detection (LOD) for the multi-mycotoxin and analyte-specific methods ranged from 0.02 to 0.41 μg/kg (μg/L) and 0.01 to 0.19 μg/L, respectively, and limits of quantification (LOQ) between 0.10 to 1.02 μg/kg (μg/L) and 0.09 to 0.47 μg/L, respectively. Apparent recoveries of the samples spiked with 0.25 to 4 μg/kg (μg/L) ranged from 60.1% to 109.8% with relative standard deviations below 15%. The methods were successfully applied to real samples. To the best of our knowledge, this is the first study carried out using a small group of patients from the Chinese population with hepatocellular carcinoma to assess their exposure to carcinogenic mycotoxins using biomarkers. Finally, the multi-mycotoxin method is a useful analytical method for assessing exposure to mycotoxins edible in animal tissues. The analyte-specific methods could be useful during toxicokinetic and toxicological studies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Cereal grains and their processed food products are frequently contaminated with mycotoxins. Among many, five major mycotoxins of aflatoxins, ochratoxins, fumonisins, deoxynivalenol, and zearalenone ...are of significant public health concern as they can cause adverse effects in humans. Being airborne or soilborne, the cosmopolitan nature of mycotoxigenic fungi contribute to the worldwide occurrence of mycotoxins. On the basis of the global occurrence data reported during the past 10 years, the incidences and maximum levels in raw cereal grains were 55% and 1642 μg/kg for aflatoxins, 29% and 1164 μg/kg for ochratoxin A, 61% and 71,121 μg/kg for fumonisins, 58% and 41,157 μg/kg, for deoxynivalenol, and 46% and 3049 μg/kg for zearalenone. The concentrations of mycotoxins tend to be lower in processed food products; the incidences varied depending on the individual mycotoxins, possibly due to the varying stability during processing and distribution of mycotoxins. It should be noted that more than one mycotoxin, produced by a single or several fungal species, may occur in various combinations in a given sample or food. Most studies reported additive or synergistic effects, suggesting that these mixtures may pose a significant threat to public health, particularly to infants and young children. Therefore, information on the co-occurrence of mycotoxins and their interactive toxicity is summarized in this paper.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK