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PubMedDate not supplied

The connection between the Penicillia and Aspergilli and mycotoxins with special emphasis on misidentified isolates.

Species of Penicillium and Aspergillus are the most potent mycotoxin producers, but the connection between species and profiles of mycotoxins has been obscured by many misidentifications of fungal isolates, especially in Penicillium. Available producers of known mycotoxins in the two important genera were examined concerning identity and production of secondary metabolites using thin-layer chromatography and high performance liquid chromatography with diode array detection. 152 isolates of Penicillium were reclassified, leaving the connection between species and mycotoxin profiles much clearer in this genus. Earlier data on mycotoxin production by different taxa were confirmed by analyzing several isolates of each taxon.

Aspergillus↗

PubMed1989

Structure-activity relationships among mycotoxins.

Relationships between structural features and biological effects of mycotoxins are reviewed. Structure-activity relationships are characterized at the molecular, subcellular, cellular, or supracellular level. Major chemical and physicochemical factors responsible for bioactivity of mycotoxins are stressed. A variety of chemical families of mycotoxins are then discussed from the point of view of structure-activity relationships. The structurally related families comprise small lactones, macrocyclic lactones, isocoumarin derivatives, aflatoxins and related compounds trichothecenes, anthraquinones, indole-derived tremorgens and selected amino acid-derived mycotoxins such as sporidesmins and cyclosporines. Biological effects of mycotoxins include acute and chronic toxicity, antimicrobial activity, mutagenicity and genotoxicity, carcinogenicity and biochemical modes of action.

Animals↗

PubMed1987

Action of tremorgenic mycotoxins on GABAA receptor.

The effects of four tremorgenic and one nontremorgenic mycotoxins were studied on gamma-aminobutyric acid (GABAA) receptor binding and function in rat brain and on binding of a voltage-operated Cl- channel in Torpedo electric organ. None of the mycotoxins had significant effect on [3H]muscimol or [3H]flunitrazepam binding to the GABAA receptor. However, only the four tremorgenic mycotoxins inhibited GABA-induced 36Cl- influx and [35S] t-butylbicyclophosphorothionate [( 35S]TBPS) binding in rat brain membranes, while the nontremorgenic verruculotoxin had no effect. Inhibition of [35S]TBPS binding by paspalinine was non-competitive. This suggests that tremorgenic mycotoxins inhibit GABAA receptor function by binding close to the receptor's Cl- channel. On the voltage-operated Cl- channel, only high concentrations of verruculogen and verruculotoxin caused significant inhibition of the channel's binding of [35S]TBPS. The data suggest that the tremorgenic action of these mycotoxins may be due in part to their inhibition of GABAA receptor function.

Animals↗

PubMed1995

Mycotoxins: risk assessment and legislation.

Mycotoxins are naturally occurring toxic secondary metabolites of fungi that may be present in food products. Several mycotoxins have been associated with and implicated in human and animal disease. Mycotoxins encompass a wide spectrum of different chemicals and they may affect many target organs and systems, notably the liver, kidney, the nervous system, the endocrine system, and the immune system. Much of our concern is about chronic effects at low levels of exposure, and several mycotoxins have been classified by the International Agency for Research in Cancer as human carcinogens or potential human carcinogens. Although these toxicants can never be completely removed from the food supply, it is possible through risk assessment to define levels that are unlikely to be of health concern. Ideally the risk assessment involves a complete toxicological assessment, an epidemiological assessment and an exposure assessment. However, in the risk management of mycotoxins it may be deemed necessary to take action before all this information is available. In this presentation recent risk management of the fumonisins will be compared with the situation for aflatoxins.

Aflatoxins↗

PubMed2026

Integrated functional, metabolomic, and biotransformation profiling of mycotoxin hepatotoxicity in 2D and 3D human hepatic models.

Mycotoxins pose a major risk to food safety and human health, yet their hepatotoxic mechanisms remain incompletely characterized due to limitations in conventional in vitro models. In this study, we systematically compared mycotoxin-induced hepatotoxicity and metabolomic profiling across two human hepatic models cultured under 2D monolayer and 3D spheroid conditions. The various mycotoxins (Aflatoxin B1, Citrinin, Deoxynivalenol, Ochratoxin A, Patulin, and Zearalenone) exhibit distinct metabolic signatures, thereby serving as an appropriate panel for comprehensively evaluating diverse hepatotoxic mechanisms. Mycotoxin exposure induced concentration-dependent hepatotoxicity accompanied by functional impairment and structural disruption in hepatic models. Metabolomic profiling revealed distinctive regulatory patterns between 2D and 3D hepatic models, with 3D spheroids showing consistent down-regulation across multiple intracellular metabolic pathways and altered extracellular metabolite release, whereas 2D monolayers predominantly exhibited global metabolic activation. In silico-assisted MS/MS analysis further demonstrated that Phase I biotransformation was largely conserved across models, whereas Phase II conjugation reactions were more frequently detected and exhibited greater model specificity in 3D spheroids. Overall, these findings indicate that 3D hepatic spheroids capture more integrated and coordinated hepatotoxic and metabolic responses to mycotoxins compared with 2D monolayer systems. These distinctive regulatory dynamics support their value as a physiologically relevant platform for toxicity assessment and mechanistic investigation.

3D hepatic spheroids↗

PubMed2006

Survey of the mycobiota of Spanish malting barley and evaluation of the mycotoxin producing potential of species of Alternaria, Aspergillus and Fusarium.

The present work deals with the toxigenic mycobiota occurring in Spanish malting barley and the capability for producing mycotoxins by several important toxigenic fungi. One hundred and eighty seven samples of malting barley were gathered from Spanish breweries before processing. One hundred and fifty kernels per sample were surface-sanitized with a 2% sodium hypochlorite solution and incubated on three culture media. The most abundant fungi were species of Alternaria, Aspergillus, Penicillium and Fusarium, which were present in 93%, 82.3%, 57.8% and 27.8% of the samples, respectively. To evaluate their mycotoxin producing potential a number of isolates belonging to each genus, except Penicillium, were randomly selected and incubated on culture media known to be appropriate for production of mycotoxins. Alternariol and alternariol monomethyl ether were produced by 26.7% of Alternaria spp. isolates (all belonged to Alternaria alternata). All tested isolates of F. verticillioides produced fumonisin B(1) (FB(1)) and 61.3% of them produced fumonisin B(2) (FB(2)), whereas FB(1) was synthesized by 83.3% and FB(2) by 77.8% of F. proliferatum isolates. Twenty percent of the isolates of the Aspergillus flavus/A. parasiticus group had the capability to produce aflatoxin B(1) and aflatoxin B(2). Thirty out of 34 isolates of F. graminearum produced deoxynivalenol and zearalenone whereas the other 4 isolates produced nivalenol. Ochratoxin A was detected in 75% and 15% of isolates of Aspergillus section Nigri and A. ochraceus, respectively. This is the first survey carried out in Spain on the toxigenic mycobiota contaminating malting barley in breweries and the mycotoxin producing capacity of several species. The information obtained is useful for assessing the risk of mycotoxins in beer.

Alternaria↗

PubMed1999

Mycotoxin contamination of maize grains grown in Karnataka (India).

One hundred and ninety seven maize samples representing different cultivars, collected from different agroclimatic regions of Karnataka (India) were analysed for moisture content, mould incidence, ergosterol and extent of mycotoxin contamination. Moisture content determination by the hot-air oven method revealed significantly high levels of moisture content (15-18%) in 34 (17%) samples, which exceeded the permissible limit for safe storage. Ergosterol quantification by HPLC revealed the presence of ergosterol in many samples collected from rural areas of Karnataka irrespective of the moisture content. Mould enumeration based on blotter and agar plating methods revealed the association of 24 diverse species of both field and storage moulds belonging to 14 genera. Mycotoxins analyses using monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) and thin-layer chromatography (TLC) revealed mycotoxin contamination in 69 (34.8%) samples. Maize samples with a high incidence of diverse species of moulds and alarmingly high levels of mycotoxins in many samples indicate the need for proper surveillance and monitoring exclusively for the prevention of moulds and mycotoxins in maize produce in Karnataka before it reaches the consumer.

Aflatoxin B1↗

PubMed2001

Mycotoxins.

Horses consume feed grains and forages that can produce a range of mycotoxins resulting from mold invasion. Toxicosis of horses often occurs from fumonisins or aflatoxin in grains, from the tremorgenic mycotoxins in dallis grass, or from slaframine in red clover. Fumonisin toxicosis often is severe and fatal, and aflatoxin can be acute or chronic and debilitating. Other mycotoxins reported in horses may cause moderate to mild signs that regress when the contaminated feedstuff is removed. Overall, horses appear to have a relatively low prevalence of reported mycotoxicoses among domestic animals, but they are extremely sensitive to the fumonisins. Since there are no good therapies for mycotoxin poisoning, attention to providing high quality grains and forages to prevent mycotoxicoses is the most effective means for reducing the risk of mycotoxins in horses.

Animal Feed↗

PubMed2006

A practical approach for identifications based on mycotoxin characters of Penicillium.

The taxonomy of the penicillia is unstable particularly in the important antibiotic and mycotoxin-producing subgenus Penicillium. There are difficulties relating identifications to mycotoxin production. Also, the validity of dual nomenclature for pleomorphic fungi is under discussion increasingly. Patulin is an important mycotoxin produced by various fungi and has strict limits in the European Union. The mycotoxin and/or the isoepoxydon dehydrogenase (IDH) gene of the metabolic pathway have been assessed in 318 strains predominately of subgenus Penicillium. These data were used to classify the isolates. Subgenus Penicillium contained most of the IDH and patulin positives. The species and varieties in subgenus Penicillium which were associated with patulin detection can be reduced to one name, viz. Penicillium Pen p+ (p = patulin). This has been extended to other mycotoxin producing penicillia to indicate the scope of the scheme. The classification will lead to the number of taxa being reduced, while avoiding species names and hence dual nomenclature. Culture independent analysis of environmental samples is mentioned. The scheme could be used with advantage for other fungi.

DNA, Fungal↗

PubMed1993

Qualitative analysis of mycotoxins using micellar electrokinetic capillary chromatography.

Naturally occurring mycotoxins are separated using micellar electrokinetic capillary chromatography. Trends in the retention of these toxins, resulting from changes in mobile-phase composition and pH, are reported and presented as a means of alleviating coelution problems. Two sets of mobile-phase conditions are determined that provide unique separation selectivity. The facile manner by which mobile-phase conditions can be altered, without changes in instrumental configuration, allowed the acquisition of two distinctive, fully resolved chromatograms of 10 mycotoxins in a period of approximately 45 min. By adjusting retention times, using indigenous or added components in mycotoxin samples as normalization standards, it is possible to obtain coefficients of variation in retention time that average less than 1%. The qualitative capabilities of this methodology are evaluated by separating randomly generated mycotoxin-interferent mixtures. In this study, the utilization of normalized retention times applied to separations obtained with two sets of mobile-phase conditions permitted the identification of all the mycotoxins in five unknown samples without any misidentifications.

Chromatography↗

PubMed2005

Immunotoxicological risk of mycotoxins for domestic animals.

Mycotoxins are a group of structurally diverse fungal secondary metabolites that elicit a wide spectrum of toxicological effects. Of particular interest is the capacity of some mycotoxins to alter normal immune function when present in food at levels below observable overt toxicity. The sensitivity of the immune system to mycotoxin-induced immunosuppression arises from the vulnerability of the continually proliferating and differentiating cells that participate in immune-mediated activities and regulate the complex communication network between cellular and humoral components. Mycotoxin-induced immunosuppression may be manifested as depressed T- or B-lymphocyte activity, suppressed antibody production and impaired macrophage/neutrophil-effector functions. The immune system is primarily responsible for defence against invading organisms. Suppressed immune function by mycotoxins may eventually decrease resistance to infectious diseases, reactivate chronic infections and/or decrease vaccine and drug efficacy.

Animals↗

PubMedDate not supplied

Rationale for regulatory programmes for mycotoxins in human foods and animal feeds.

Currently, more than 50 countries have enacted or proposed regulations for mycotoxins in food and feed. There are various factors that may influence the establishment of tolerances for certain mycotoxins, such as the availability of toxicological data, the availability of data on dietary exposure, the distribution of mycotoxins over commodities, legislation of other countries with which trade contacts exist, and the availability of methods of analysis. In practice, only few countries have formally presented the rationale for the need to regulate, or for the selection of a particular maximum tolerated level, as a recent international enquiry demonstrated. Most of the limits for aflatoxins in food were based on rather vague statements of the carcinogenic risk for humans. There was a general consensus that exposure to a potential human carcinogen that could not be totally avoided should be limited to the lowest practical level. Several countries made a claim to a hazard evaluation (Belgium, Canada, India, The Netherlands, Switzerland, South Africa, United Kingdom, United States), although specifics were rather scarce. No rationales for setting limits for other mycotoxins were provided, except for Canada, where risk assessment was done for deoxynivalenol, zearalenone and ochratoxin A. It is apparent that in most countries either the scientific basis for regulation of mycotoxins is non-existent, or the science has not been fully utilized.

Aflatoxins↗

PubMedDate not supplied

Mycotoxins: regulations, quality assurance and reference materials.

Some 60 countries have currently enacted or proposed regulations for control of mycotoxins (primarily the aflatoxins) in food and animal feed. Various factors influence the establishment of limits for certain mycotoxins, but there is no consistent rationale for setting limits or for enforcement control. The enforcement of the regulations requires monitoring of suspected commodities. Many laboratories perform large numbers of determinations of mycotoxins, in particular aflatoxins, and consider their results to be reliable. Nevertheless, it often happens that laboratories find quite different analytical results on samples that have been especially homogenized for interlaboratory studies. The application of Quality Assurance principles contributes to the reliability of mycotoxin measurements. Quality Assurance is focused on the organizational process and the conditions under which laboratory studies are planned, performed, monitored, recorded, reported and archived. This is, in itself, an important contribution to the scientific value of a study. A Quality Assurance programme should include various elements, including (certified) reference materials, if available. Certified reference materials are stable, homogeneous products with certified values of the analyte(s) of interest. Various certified reference materials for mycotoxins have been prepared by the European Commission's Community Bureau of Reference, in co-operation with several European laboratories (aflatoxin M1 in milk powder, aflatoxins B1 B2, G1, and G2 in peanut butter, aflatoxin B1 in peanut meal and compound feed, deoxynivalenol in wheat and maize flour). Other reference materials are in a well-advanced development stage (ochratoxin A in wheat flour and pig kidney, fumonisins B1 and B2 in maize).

Food Contamination↗

PubMed1996

Survey of ethnic foods for mycotoxins.

A survey has been carried out in the UK to determine the levels of mycotoxins in a range of ethnic foods. The survey involved analysis of 121 samples of ethnic foods, purchased from specialist shops, for aflatoxins, ochratoxin A and the Fusarium mycotoxins (fumonisins, zearalenone and trichothecenes). The samples were of cereal and cereal product, fats and oils, nuts and nut products, seeds, spices and herbs, pickles, sauces and a variety of canned vegetable and/or pickle products. Low concentrations of mycotoxins were present in many samples analysed. The types and levels of mycotoxins present varied with the type of sample. The most common contaminants were the trichothecenes and ochratoxin A. Trace levels of aflatoxins, ochratoxin A, zearalenone, fumonisins and trichothecenes were detected in samples containing cereal, such as rice, noodles, corn flour and pitta bread. Trace levels of aflatoxins and zearalenone were detected in a sample of chili oil and ochratoxin A in a sample of sesame oil. Only one sample of nut (almond) contained aflatoxin while aflatoxins, ochratoxin A, zearalenone and deoxynivalenol (a trichothecene) were detected in various seeds. Aflatoxins, ochratoxin A and fumonisins were found in chili paste and zearalenone and ochratoxin A in curry pastes. The highest mycotoxin levels and frequency of occurrence were in chili powder, curry powder and ginger.

Chromatography, High Pressure Liquid↗

PubMed2006

The incidence of fungi and mycotoxins in South Africa wheat and wheat-based products.

This investigation was undertaken to survey the fungal and mycotoxin contamination of South African wheat ranging from that growing in the field to processed wheat products. Samples of wheat were taken from various growing areas in South Africa and screened for fungi and mycotoxins, using a range of methodologies, including chromatography, immunoaffinity/fluorimetry, and cytotoxicity testing. Similar samples were taken from supermarkets and retail outlets in South Africa and analyzed in a similar manner. The result showed that a range of fungi and mycotoxins could be detected in wheat in all these sample types. The major fungal contaminants were Fusarium spp. and their attendant mycotoxins, in particular deoxynivalenol, which is in keeping with the observations made in the rest of the world. An interesting observation was that samples of wheat taken from the field with heavy Fusarium contamination were contaminated with fumonisin B1, which is not normally associated with this crop. Of more concern were the low but persistent levels of mycotoxins and fungi in wheat-based products sold directly to the public.

Consumer Product Safety↗

PubMed2005

Effect of mycotoxins on some activities of isolated human neutrophils.

Activities of mycotoxins--citrinin, ochratoxin B, rubratoxin B, and zearalenol beta--that affected superoxide anion (O2-) production were studied on human neutrophils with regard to hypochlorous acid (HOCl) generation, nitric oxide (NO) formation, and chemotaxis of isolated cells. At the doses of 10(-8), 10(-6), 10(-4), or 10(-2) mg/mL, in stimulated cells the mycotoxins inhibited HOCl production proportionally to that of O2- because HOCl production is directly dependent on O2- generation. But unlike the others, zearalenol beta decreased HOCl production much more than one of O2-, indicating an effect also on myeloperoxidase secretion. All mycotoxins inhibited NO generation but only at the dose of 10(-2) mg/mL. Formyl-met-leu-phe-induced chemotaxis of neutrophils was deeply affected as well, as all mycotoxins at all doses used decreased it. All considered effects were not dose-dependent, likely connected to high variability of individual sensitivity to these compounds and because they already are present in blood introduced with foods. These activities of neutrophils confirm and extend the danger for immune systems by mycotoxins also in very small quantities, since the smaller concentrations we used are easily reachable in blood.

Chemotaxis, Leukocyte↗

PubMed2006

Toxigenic Fusarium spp. as determinants of trichothecene mycotoxins in settled grain dust.

Trichothecenes are immunosuppressive mycotoxins produced mainly by Fusarium spp. and often are detected as natural contaminants of grain and other agricultural products. Exposure to trichothecenes through inhalation during grain work may represent possible health risks for grain farmers. We aimed, therefore, to investigate the level of Fusarium spp. and trichothecenes in settled grain dust collected during work on 92 Norwegian farms. Mycotoxins were determined by gas chromatography-mass spectrometry, whereas the Fusarium spp. were identified and quantified both by species-specific semiquantitative polymerase chain reaction (PCR) and by cultivation. All potential trichothecene-producing molds in the grain dust were quantified using a PCR assay specific for tri5, the gene coding for trichodiene synthase that catalyzes the first step in the trichothecene biosynthesis. We performed correlation analysis between mold-DNA and mycotoxins to assess whether the PCR-detected DNA could be used as indicators of the mycotoxins. The methodological problem of detecting small amounts of airborne mycotoxins during grain work may then be avoided. Whereas the trichothecene-producing Fusarium species in grain dust could not be identified or quantified to a sufficient extent by cultivation, all investigated Fusarium spp. could be specifically detected by PCR and quantified from the DNA agarose gel band intensities. Furthermore, we observed a strong correlation between the trichothecenes HT-2 toxin (HT-2) or T-2 toxin (T-2) and DNA specific for tri5 (r = 0.68 for HT-2 and r = 0.50 for T-2; p < 0.001), F. langsethiae (r = 0.77 for HT-2 and r = 0.59 for T-2; p < 0.001), or F. poae (r = 0.41 for HT-2 and r = 0.35 for T-2; p < 0.001). However, only a moderate correlation was observed between the trichothecene deoxynivalenol (DON) and the combination of its producers, F. culmorum and F. graminearum (r = 0.24, p = 0.02), and no significant correlation was observed between DON and tri5. PCR clearly improved the detection of toxigenic Fusaria as potential sources of health risks for farmers inhaling grain dust during work, but the use of Fusarium-DNA as indicators for trichothecenes should be used cautiously.

DNA, Fungal↗

PubMed2004

Effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on growth and immunological parameters of broiler chickens.

An experiment was conducted to investigate the effects of feeding grains naturally contaminated with Fusarium mycotoxins on growth and immunological parameters of broiler chickens. Three hundred sixty, 1-d-old male broiler chicks were fed 1 of 4 diets containing grains naturally contaminated with Fusarium mycotoxins for 56 d. The diets included (1) control; (2) low level of contaminated grains (5.9 mg/kg deoxynivalenol (DON), 19.1 mg/kg fusaric acid (FA), 0.4 mg/kg zearalenone, and 0.3 mg/kg 15-acetyldeoxynivalenol; (3) high level of contaminated grains (9.5 mg/kg DON, 21.4 mg/kg FA, 0.7 mg/kg zearalenone, and 0.5 mg/kg 15-acetyldeoxynivalenol); and (4) high level of contaminated grains + 0.2% polymeric glucomannan mycotoxin adsorbent (GM polymer). Body weight gains and feed consumption of chickens fed contaminated grains decreased linearly with the inclusion of contaminated grains during the grower phase (d 21 to 42). Efficiency of feed utilization, however, was not affected by diet. Production parameters were not significantly affected by the supplementation of GM polymer to the contaminated grains. Peripheral blood monocytes decreased linearly in birds fed contaminated grains. The feeding of contaminated diets linearly reduced the B-cell count at the end of the experiment, whereas the T-cell count on d 28 responded quadratically to the contaminated diets. The feeding of contaminated diets did not significantly alter serum or bile immunoglobulin concentrations, contact hypersensitivity to dinitrochlorobenzene, or antibody response to SRBC. Supplementation with GM polymer in the contaminated diet nonspecifically increased white blood cell count and lymphocyte count, while preventing mycotoxin-induced decreases in B-cell counts. It was concluded that broiler chickens are susceptible during extended feeding of grains naturally contaminated with Fusarium mycotoxins.

Animal Feed↗