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"deoxynivalenol"
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Risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed
by
van Manen, Mathijs
,
Rose, Martin
,
van Egmond, Hans
in
15‐acetyl‐deoxynivalenol
,
3‐acetyl‐deoxynivalenol
,
Animal biology
2017
Deoxynivalenol (DON) is a mycotoxin primarily produced by Fusarium fungi, occurring predominantly in cereal grains. Following the request of the European Commission, the CONTAM Panel assessed the risk to animal and human health related to DON, 3‐acetyl‐DON (3‐Ac‐DON), 15‐acetyl‐DON (15‐Ac‐DON) and DON‐3‐glucoside in food and feed. A total of 27,537, 13,892, 7,270 and 2,266 analytical data for DON, 3‐Ac‐DON, 15‐Ac‐DON and DON‐3‐glucoside, respectively, in food, feed and unprocessed grains collected from 2007 to 2014 were used. For human exposure, grains and grain‐based products were main sources, whereas in farm and companion animals, cereal grains, cereal by‐products and forage maize contributed most. DON is rapidly absorbed, distributed, and excreted. Since 3‐Ac‐DON and 15‐Ac‐DON are largely deacetylated and DON‐3‐glucoside cleaved in the intestines the same toxic effects as DON can be expected. The TDI of 1 μg/kg bw per day, that was established for DON based on reduced body weight gain in mice, was therefore used as a group‐TDI for the sum of DON, 3‐Ac‐DON, 15‐Ac‐DON and DON‐3‐glucoside. In order to assess acute human health risk, epidemiological data from mycotoxicoses were assessed and a group‐ARfD of 8 μg/kg bw per eating occasion was calculated. Estimates of acute dietary exposures were below this dose and did not raise a health concern in humans. The estimated mean chronic dietary exposure was above the group‐TDI in infants, toddlers and other children, and at high exposure also in adolescents and adults, indicating a potential health concern. Based on estimated mean dietary concentrations in ruminants, poultry, rabbits, dogs and cats, most farmed fish species and horses, adverse effects are not expected. At the high dietary concentrations, there is a potential risk for chronic adverse effects in pigs and fish and for acute adverse effects in cats and farmed mink.
Journal Article
Natural Occurrence of Deoxynivalenol and Its Acetylated Derivatives in Chinese Maize and Wheat Collected in 2017
by
Liu, Yan
,
Yan, Pianpian
,
Liu, Shiqiao
in
15-acetyl-deoxynivalenol
,
3-acetyl-deoxynivalenol
,
Acetylation
2020
Deoxynivalenol (DON), along with 3-acetyl-deoxynivalenol (3-ADON) and 15-acetyl-deoxynivalenol (15-ADON), occur in grains and cereal products and is often hazardous to humans and livestock. In this study, 579 wheat samples and 606 maize samples intended for consumption were collected from China in 2017 and analyzed to determine the co-occurrence of type-B trichothecenes (DON, 3-ADON, and 15-ADON). All the wheat samples tested positive for DON, while 99.83% of the maize samples were DON-positive with mean DON concentrations of 165.87 and 175.30 μg/kg, respectively. Per the Chinese standard limits for DON, 3.63% of wheat and 2.97% of the maize samples were above the maximum limit of 1000 μg/kg. The DON derivatives (3-ADON and 15-ADON) were less frequently found and were present at lower levels than DON in wheat. 3-ADON and 15-ADON had incidences of 13.53% and 76.40%, respectively, in maize. By analyzing the distribution ratio of DON and its derivatives in wheat and maize, DON (95.51%) was the predominant toxin detected in wheat samples, followed by 3.97% for the combination of DON + 3-ADON, while DON + 3-ADON + 15-ADON and DON + 15-ADON were only found in 0.17% and 0.35% of wheat samples, respectively. Additionally, a large amount of the maize samples were contaminated with DON + 15-ADON (64.19%) and DON (22.11%). The samples with a combination of DON + 3-ADON and DON + 3-ADON + 15-ADON accounted for 1.32% and 12.21%, respectively. Only one maize sample did not contain all three mycotoxins. Our study shows the necessity of raising awareness of the co-occurrence of mycotoxin contamination in grains from China to protect consumers from the risk of exposure to DON and its derivatives.
Journal Article
Occurrence of Fusarium Mycotoxins and Their Modified Forms in Forage Maize Cultivars
by
Jensen, Tolke
,
Sönnichsen, Frank D.
,
De Saeger, Sarah
in
3-acetyl-deoxynivalenol
,
Barley
,
Cereals
2021
Forage maize is often infected by mycotoxin-producing Fusarium fungi during plant growth, which represent a serious health risk to exposed animals. Deoxynivalenol (DON) and zearalenone (ZEN) are among the most important Fusarium mycotoxins, but little is known about the occurrence of their modified forms in forage maize. To assess the mycotoxin contamination in Northern Germany, 120 natural contaminated forage maize samples of four cultivars from several locations were analysed by liquid chromatography-high resolution mass spectrometry (LC-HRMS) for DON and ZEN and their modified forms deoxynivalenol-3-glucoside (DON3G), the sum of 3- and 15-acetyl-deoxynivalenol (3+15-AcDON), α- and β-zearalenol (α-ZEL, β-ZEL). DON and ZEN occurred with high incidences (100 and 96%) and a wide range of concentrations, reaching levels up to 10,972 and 3910 µg/kg, respectively. Almost half of the samples (46%) exceeded the guidance value in complementary and complete feeding stuffs for ZEN (500 µg/kg), and 9% for DON (5000 µg/kg). The DON related mycotoxins DON3G and 3+15-AcDON were also present in almost all samples (100 and 97%) with amounts of up to 3038 and 2237 µg/kg and a wide range of concentrations. For the ZEN metabolites α- and β-ZEL lower incidences were detected (59 and 32%) with concentrations of up to 423 and 203 µg/kg, respectively. Forage maize samples were contaminated with at least three co-occurring mycotoxins, whereby 95% of all samples contained four or more mycotoxins with DON, DON3G, 3+15-AcDON, and ZEN co-occurring in 93%, together with α-ZEL in 57% of all samples. Positive correlations were established between concentrations of the co-occurring mycotoxins, especially between DON and its modified forms. Averaged over all samples, ratios of DON3G/DON and 3+15-AcDON/DON were similar, 20.2 and 20.5 mol%; cultivar-specific mean ratios ranged from 14.6 to 24.3 mol% and 15.8 to 24.0 mol%, respectively. In total, 40.7 mol% of the measured DON concentration was present in the modified forms DON3G and 3+15-AcDON. The α-ZEL/ZEN ratio was 6.2 mol%, ranging from 5.2 to 8.6 mol% between cultivars. These results demonstrate that modified mycotoxins contribute substantially to the overall mycotoxin contamination in forage maize. To avoid a considerable underestimation, it is necessary to analyse modified mycotoxins in future mycotoxin monitoring programs together with their parent forms.
Journal Article
Mycotoxins in maize: mitigation actions, with a chain management approach
2020
Maize is the principal staple food/feed crop exposed to mycotoxins, and the co-occurrence of multiple mycotoxins and their metabolites has been well documented. This review presents the infection cycle, ecology, and plant-pathogen interactions of Aspergillus and Fusarium species in maize, and current knowledge on maize chain management to mitigate the occurrence of aflatoxins and fumonisins. Preventive actions include at pre-harvest, as part of cropping systems, at harvest, and at post-harvest, through storage, processing, and detoxification to minimize consumer exposure. Preventive actions in the field have been recognized as efficient for reducing the entrance of mycotoxins into production chains. Biological control of Aspergillus flavus has been recognized to minimize contamination with aflatoxins. Post-harvest maize grain management is also crucial to complete preventive actions, and has been made mandatory in government food and feed legislation.
Journal Article
Diametral influence of deoxynivalenol (DON) and deepoxy-deoxynivalenol (DOM-1) on the growth of Campylobacter jejuni with consequences on the bacterial transcriptome
by
Hess, Claudia
,
Schatzmayr, Dian
,
Grenier, Bertrand
in
Acclimation
,
Acclimatization
,
Animal Feed - microbiology
2024
Background
Deoxynivalenol (DON) is a type B trichothecene mycotoxin that is commonly found in cereals and grains worldwide. The presence of this fungal secondary-metabolite raises public-health concerns at both the agriculture and food industry level. Recently, we have shown that DON has a negative impact on gut integrity, a feature also noticed for
Campylobacter (C.) jejuni
. We further demonstrated that DON increased the load of
C. jejuni
in the gut and inner organs. In contrast, feeding the less toxic DON metabolite deepoxy-deoxynivalenol (DOM-1) to broilers reduced the
Campylobacter
load in vivo. Consequently, it can be hypothesized that DON and DOM-1 have a direct effect on the growth profile of
C. jejuni
. The aim of the present study was to further resolve the nature of this interaction in vitro by co-incubation and RNA-sequencing.
Results
The co-incubation of
C. jejuni
with DON resulted in significantly higher bacterial growth rates from 30 h of incubation onwards. On the contrary, the co-incubation of
C. jejuni
with DOM-1 reduced the CFU counts, indicating that this DON metabolite might contribute to reduce the burden of
C. jejuni
in birds, altogether confirming in vivo data. Furthermore, the transcriptomic profile of
C. jejuni
following incubation with either DON or DOM-1 differed. Co-incubation of
C. jejuni
with DON significantly increased the expression of multiple genes which are critical for
Campylobacter
growth, particularly members of the Flagella gene family, frr (ribosome-recycling factor), PBP2 futA-like (Fe
3+
periplasmic binding family) and PotA (ATP-binding subunit). Flagella are responsible for motility, biofilm formation and host colonization, which may explain the high
Campylobacter
load in the gut of DON-fed broiler chickens. On the contrary, DOM-1 downregulated the Flagella gene family and upregulated ribosomal proteins.
Conclusion
The results highlight the adaptive mechanisms involved in the transcriptional response of
C. jejuni
to DON and its metabolite DOM-1, based on the following effects: (a) ribosomal proteins; (b) flagellar proteins; (c) engagement of different metabolic pathways. The results provide insight into the response of an important intestinal microbial pathogen against DON and lead to a better understanding of the luminal or environmental acclimation mechanisms in chickens.
Journal Article
Plant defense compound triggers mycotoxin synthesis by regulating H2B ub1 and H3K4 me2/3 deposition
2021
• Fusarium graminearum produces the mycotoxin deoxynivalenol (DON) which promotes its expansion during infection on its plant host wheat. Conditional expression of DON production during infection is poorly characterized.
• Wheat produces the defense compound putrescine, which induces hypertranscription of DON biosynthetic genes (FgTRIs) and subsequently leads to DON accumulation during infection. Further, the regulatory mechanisms of FgTRIs hypertranscription upon putrescine treatment were investigated.
• The transcription factor FgAreA regulates putrescine-mediated transcription of FgTRIs by facilitating the enrichment of histone H2B monoubiquitination (H2B ub1) and histone 3 lysine 4 di- and trimethylations (H3K4 me2/3) on FgTRIs. Importantly, a DNA-binding domain (bZIP) specifically within the Fusarium H2B ub1 E3 ligase Bre1 othologs is identified, and the binding of this bZIP domain to FgTRIs depends on FgAreA-mediated chromatin rearrangement. Interestingly, H2B ub1 regulates H3K4 me2/3 via the methyltransferase complex COMPASS component FgBre2, which is different from Saccharomyces cerevisiae.
• Taken together, our findings reveal the molecular mechanisms by which host-generated putrescine induces DON production during F. graminearum infection. Our results also provide a novel insight into the role of putrescine during phytopathogen–host interactions and broaden our knowledge of H2B ub1 biogenesis and crosstalk between H2B ub1 and H3K4 me2/3 in eukaryotes.
Journal Article
Glucuronidation of deoxynivalenol (DON) by different animal species: identification of iso-DON glucuronides and iso-deepoxy-DON glucuronides as novel DON metabolites in pigs, rats, mice, and cows
2017
The
Fusarium
mycotoxin deoxynivalenol (DON) is a frequent contaminant of cereal-based food and feed. Mammals metabolize DON by conjugation to glucuronic acid (GlcAc), the extent and regioselectivity of which is species-dependent. So far, only DON-3-glucuronide (DON-3-GlcAc) and DON-15-GlcAc have been unequivocally identified as mammalian DON glucuronides, and DON-7-GlcAc has been proposed as further DON metabolite. In the present work, qualitative HPLC–MS/MS analysis of urine samples of animals treated with DON (rats: 2 mg/kg bw, single bolus, gavage; mice: 1 mg/kg bw, single i.p. injection; pigs: 74 µg/kg bw, single bolus, gavage; cows: 5.2 mg DON/kg dry mass, oral for 13 weeks) revealed additional DON and deepoxy-DON (DOM) glucuronides. To elucidate their structures, DON and DOM were incubated with human (HLM) and rat liver microsomes (RLM). Besides the expected DON/DOM-3- and 15-GlcAc, minor amounts of four DON- and four DOM glucuronides were formed. Isolation and enzymatic hydrolysis of four of these compounds yielded iso-DON and iso-DOM, the identities of which were eventually confirmed by NMR. Incubation of iso-DON and iso-DOM with RLM and HLM yielded two main glucuronides for each parent compound, which were isolated and identified as iso-DON/DOM-3-GlcAc and iso-DON/DOM-8-GlcAc by NMR. Iso-DON-3-GlcAc, most likely misidentified as DON-7-GlcAc in the literature, proved to be a major DON metabolite in rats and a minor metabolite in pigs. In addition, iso-DON-8-GlcAc turned out to be one of the major DON metabolites in mice. DOM-3-GlcAc was the dominant DON metabolite in urine of cows and an important DON metabolite in rat urine. Iso-DOM-3-GlcAc was detected in urine of DON-treated rats and cows. Finally, DON-8,15-hemiketal-8-glucuronide, a previously described by-product of DON-3-GlcAc production by RLM, was identified in urine of DON-exposed mice and rats. The discovery of several novel DON-derived glucuronides in animal urine requires adaptation of the currently used methods for DON-biomarker analysis.
Journal Article
Deoxynivalenol and its toxicity
2010
Deoxynivalenol (DON) is one of several mycotoxins produced by certain Fusarium species that frequently infect corn, wheat, oats, barley, rice, and other grains in the field or during storage. The exposure risk to human is directly through foods of plant origin (cereal grains) or indirectly through foods of animal origin (kidney, liver, milk, eggs). It has been detected in buckwheat, popcorn, sorgum, triticale, and other food products including flour, bread, breakfast cereals, noodles, infant foods, pancakes, malt and beer. DON affects animal and human health causing acute temporary nausea, vomiting, diarrhea, abdominal pain, headache, dizziness, and fever. This review briefly summarizes toxicities of this mycotoxin as well as effects on reproduction and their antagonistic and synergic actions.
Journal Article
Deoxynivalenol and Its Modified Forms: Are There Major Differences?
by
Braber, Saskia
,
Garssen, Johan
,
Alizadeh, Arash
in
15-acetyl-deoxynivalenol
,
3-acetyl-deoxynivalenol
,
Caco-2 Cells
2016
Considering the diverse toxic effects of the Fusarium toxin deoxynivalenol (DON), its common occurrence in wheat-based products, and its stability during processing, DON constitutes an increasing health concern for humans and animals. In addition to the parent compound DON, human and animal exposure encompasses the acetylated fungal metabolites 3-acetyl-deoxynivalenol (3ADON) and 15-acetyl-deoxynivalenol (15ADON) as well as the plant-derived DON-glucoside (DON3G) and the bacterial product de-epoxy-DON (DOM-1). In the current study we used the well-established Caco-2 cell model to compare the effects of these naturally occurring forms of DON on cell viability and markers of barrier integrity, as well as on the release of the pro-inflammatory chemokine chemokine CXC motif ligand (CXCL8). Results show that 3ADON is less potent in inducing adverse effects on barrier integrity when compared to DON, whereas 15ADON appears to be slightly more potent than DON. In contrast, DON3G and DOM-1 exerted no measurable adverse effects on the intestinal barrier. It was also demonstrated that galacto-oligosaccharides (GOS) are able to protect epithelial cells against DON and its acetylated forms, which suggests that GOS are beneficial food additives in the protection of vulnerable segments of the human population against adverse effects of DON and its derivatives.
Journal Article
Deoxynivalenol Decontamination in Raw and Germinating Barley Treated by Plasma-Activated Water and Intense Pulsed Light
2019
The contamination of barley kernel by
Fusarium
fungi constitutes a serious problem for malting-related industries. Deoxynivalenol (DON) is a secondary metabolite produced by
Fusarium
fungi. DON can affect dopaminergic receptors in the human brain; it may cause symptoms such as vomiting, diarrhea, headache, and fever. The aims of this study were to evaluate the DON destruction effect of the intense pulsed light (IPL) and plasma-activated water (PAW) treatments in raw and germinating barley and assess the feasibility for disinfection in the malt industry. Both non-thermal methods degraded DON concentration in germinating barley. IPL treatment significantly reduced (
p
< 0.05) the DON level of germinating barley samples by 35.5% after 180 pulses in 60 s, and the PAW treatment effectively degraded the DON level by 34.6% in germinating barley in the first 5 min. However, higher barley quality remained for PAW treatment (germination rate: 81–100%) than for the IPL treatment (germination rate: 41–60%). For the raw barley samples, although significant reduction (30.9%) was achieved after 180 pulses of IPL treatment, noticeable quality (germination rate: 20–40%) alteration was observed. Significantly less DON degradation was achieved by the PAW treatment on raw barley than the germinating barley for all times. Overall, these findings suggested that PAW and IPL might potentially be used to reduce DON levels in some malt-related industry applications, and PAW was recommended as a better method than IPL to maintain the barley quality.
Journal Article