Special Issue "Biomonitoring of Mycotoxins"

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Mycotoxins".

Deadline for manuscript submissions: closed (31 May 2021).

Special Issue Editor

Dr. Carlo Brera
E-Mail
Guest Editor
Italian National Institute of Health (ISS), 00161 Rome, Italy
Interests: risk/exposure assessment of mycotoxins; biomonitoring studies; monitoring plans on mycotoxins
Special Issues and Collections in MDPI journals

Special Issue Information

The One Health approach linking the triad of environment–food–human beings is a promising frontier in getting information on the sources of the complex mixture of chemicals to which people are daily exposed.

With the aim to assess human exposure to contaminants and to raise the level of information on the association of their toxic effects on public health, human biomonitoring studies represent a valuable approach complementary to the classic estimates of exposure based on food consumption. Biomarkers have been employed as a tool for the assessment of the intake of a food contaminants over a number of years with success, since their measurement may give evidence of the consumption of contaminated food. Among contaminants, mycotoxins represent one of the most challenging burdens to the above-mentioned triad entailing environmental, agronomic, economic, health, and ethical aspects.

Biomonitoring studies on mycotoxins have been increasing considerably during the last 10 years. However, a lack of harmonization in the experimental settings and design, in the definition of performance criteria of analytical methods, and in the data collection is still present in combination with scarce information on the physiological data of excretion of validated biomarkers. These drawbacks make the exploitation of these data difficult in an exposure assessment context. Conversely, they have indubitable advantages for measuring exposure over time, for estimating exposure directly, and for assessing individual estimates (especially for specific subpopulations, e.g., vegetarians, Celiacs).

From the above, with the aim to contribute to making a step forward in the reliability of human and animal exposure assessment, this Special Issue will preferentially consider for publication recent papers on biomonitoring of mycotoxins dealing with the acquisition of crucial knowledge to improve the reliability of human and animal exposure assessment.

Dr. Carlo Brera
Guest Editor

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Keywords

  • Mycotoxins (or the single ones, aflatoxins, ochratoxin A, fumonisins, T2/HT2 toxins, zearalenone, deoxynivalenol)
  • Biomarkers
  • Biological fluids
  • Exposure assessment
  • Risk assessment

Published Papers (10 papers)

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Research

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Article
Biomonitoring of Mycotoxins in Plasma of Patients with Alzheimer’s and Parkinson’s Disease
Toxins 2021, 13(7), 477; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13070477 - 10 Jul 2021
Viewed by 424
Abstract
Exposure to environmental contaminants might play an important role in neurodegenerative disease pathogenesis, such as Parkinson´s disease (PD) and Alzheimer´s disease (AD). For the first time in Spain, the plasmatic levels of 19 mycotoxins from patients diagnosed with a neurodegenerative disease (44 PD [...] Read more.
Exposure to environmental contaminants might play an important role in neurodegenerative disease pathogenesis, such as Parkinson´s disease (PD) and Alzheimer´s disease (AD). For the first time in Spain, the plasmatic levels of 19 mycotoxins from patients diagnosed with a neurodegenerative disease (44 PD and 24 AD) and from their healthy companions (25) from La Rioja region were analyzed. The studied mycotoxins were aflatoxins B1, B2, G1, G2 and M1, T-2 and HT-2, ochratoxins A (OTA) and B (OTB), zearalenone, sterigmatocystin (STER), nivalenol, deoxynivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, deepoxy-deoxynivalenol, neosolaniol, diacetoxyscirpenol and fusarenon-X. Samples were analyzed by LC-MS/MS before and after treatment with β-glucuronidase/arylsulfatase in order to detect potential metabolites. Only OTA, OTB and STER were detected in the samples. OTA was present before (77% of the samples) and after (89%) the enzymatic treatment, while OTB was only detectable before (13%). Statistically significant differences in OTA between healthy companions and patients were observed but the observed differences might seem more related to gender (OTA levels higher in men, p-value = 0.0014) than the disease itself. STER appeared only after enzymatic treatment (88%). Statistical analysis on STER, showed distributions always different between healthy controls and patients (patients’ group > controls, p-value < 0.0001). Surprisingly, STER levels weakly correlated positively with age in women (rho = 0.3384), while OTA correlation showed a decrease of levels with age especially in the men with PD (rho = −0.4643). Full article
(This article belongs to the Special Issue Biomonitoring of Mycotoxins)
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Article
Assessment of Mycotoxin Exposure in a Rural County of Chile by Urinary Biomarker Determination
Toxins 2021, 13(7), 439; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13070439 - 25 Jun 2021
Viewed by 680
Abstract
Aflatoxin B1 (AFB1), ochratoxin A (OTA), zearalenone (ZEN), and deoxynivalenol (DON) are frequent mycotoxins that may cause carcinogenic, mutagenic, estrogenic, or gastrointestinal effects. The aim of this study was to assess the exposure to and risk from AFB1, OTA, ZEN, and DON in [...] Read more.
Aflatoxin B1 (AFB1), ochratoxin A (OTA), zearalenone (ZEN), and deoxynivalenol (DON) are frequent mycotoxins that may cause carcinogenic, mutagenic, estrogenic, or gastrointestinal effects. The aim of this study was to assess the exposure to and risk from AFB1, OTA, ZEN, and DON in 172 participants of the Maule Cohort (MAUCO) by a biomarker analysis in urine and to associate their exposure with food consumption and occupation. Mycotoxins in the first morning urine were analyzed by solid-phase extraction and quantified by Ultra-High-Performance Liquid Chromatography with a mass–mass detector. Participants’ information regarding food consumption, occupation, and other characteristics was obtained from a baseline and 2-year follow-up survey of the cohort. The prevalence and mean levels of mycotoxins in the urine were as follows: DON 63%, 60.7 (±78.7) ng/mL; AFB1 8%, 0.3 (±0.3) ng/mL; α-zearalenol (α-ZEL) 4.1%, 41.8 (±115) ng/mL; β-ZEL 3.5%, 17.4 (±16.1) ng/mL; AFM1 2%, 1.8 (±1.0) ng/mL; OTA 0.6% (1/172), 1.3 ng/mL; and ZEN 0.6%, 1.1 ng/mL. These results were translated into exposures of DON, ZEN, and aflatoxins of public health concern. Participants who consumed coffee and pepper the day before had a significantly greater presence of DON (OR: 2.3, CI95 1.17–4.96) and total ZEL (OR: 14.7, CI95 3.1–81.0), respectively, in their urine. Additionally, we observed associations between the habitual consumption of beer and DON (OR: 2.89, CI95 1.39–6.42). Regarding the levels of mycotoxins and the amount of food consumed, we found correlations between DON and nuts (p = 0.003), total ZEL and cereals (p = 0.01), and aflatoxins with capsicum powder (p = 0.03) and walnuts (p = 0.03). Occupation did not show an association with the presence of mycotoxins in urine. Full article
(This article belongs to the Special Issue Biomonitoring of Mycotoxins)
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Article
Determination of Urinary Mycotoxin Biomarkers Using a Sensitive Online Solid Phase Extraction-UHPLC-MS/MS Method
Toxins 2021, 13(6), 418; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13060418 - 11 Jun 2021
Viewed by 765
Abstract
In the course of assessing the human exposure to mycotoxins, biomarker-based approaches have proven to be important tools. Low concentration levels, complex matrix compositions, structurally diverse analytes, and the large size of sample cohorts are the main challenges of analytical procedures. For that [...] Read more.
In the course of assessing the human exposure to mycotoxins, biomarker-based approaches have proven to be important tools. Low concentration levels, complex matrix compositions, structurally diverse analytes, and the large size of sample cohorts are the main challenges of analytical procedures. For that reason, an online solid phase extraction-ultra high-performance liquid chromatography-tandem mass spectrometry (online SPE-UHPLC-MS/MS) method was developed, allowing for the sensitive, robust, and rapid analysis of 11 relevant mycotoxins and mycotoxin metabolites in human urine. The included spectrum of analytes comprises aflatoxin M1 (AFM1), altenuene (ALT), alternariol monomethyl ether (AME), alternariol (AOH), citrinin (CIT) and its metabolite dihydrocitrinone (DH-CIT), fumonisin B1 (FB1), ochratoxin A (OTA), and zearalenone (ZEN) as well as α- and β-zearalenol (α- and β-ZEL). Reliable quantitation was achieved by means of stable isotope dilution, except for ALT, AME and AOH using matrix calibrations. The evaluation of method performance displayed low limits of detection in the range of pg/mL urine, satisfactory apparent recovery rates as well as high accuracy and precision during intra- and interday repeatability. Within the analysis of Zimbabwean urine samples (n = 50), the applicability of the newly developed method was shown. In addition to FB1 being quantifiable in all analyzed samples, six other mycotoxin biomarkers were detected. Compared to the occurrence rates obtained after analyzing the same sample set using an established dilute and shoot (DaS) approach, a considerably higher number of positive samples was observed when applying the online SPE method. Owing to the increased sensitivity, less need of sample handling, and low time effort, the herein presented online SPE approach provides a valuable contribution to human biomonitoring of mycotoxin exposure. Full article
(This article belongs to the Special Issue Biomonitoring of Mycotoxins)
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Article
Analysis of Multiple Mycotoxins in the Qatari Population and Their Relation to Markers of Oxidative Stress
Toxins 2021, 13(4), 267; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13040267 - 08 Apr 2021
Viewed by 517
Abstract
Mycotoxins are naturally occurring food toxins worldwide that can cause serious health effects. The measurement of mycotoxin biomarkers in biological fluids is needed to assess individuals’ exposure. The aim of this study was to investigate the incidence of mycotoxins in the Qatari population. [...] Read more.
Mycotoxins are naturally occurring food toxins worldwide that can cause serious health effects. The measurement of mycotoxin biomarkers in biological fluids is needed to assess individuals’ exposure. The aim of this study was to investigate the incidence of mycotoxins in the Qatari population. Serum samples from 412 adults and urinary samples from 559 adults were analyzed for the presence of mycotoxin biomarkers. Multimycotoxin approaches have been applied, using liquid chromatography mass spectrometry methods. Samples were further analyzed for the oxidative stress markers and compared with regard to the incidence of mycotoxins. The presence of mycotoxins was identified in 37% of serum samples and in less than 20% of urine samples. It was found that 88% of positive of the samples were positive for only one mycotoxin, while 12% of positive samples had two or more mycotoxins. Trichothecenes and zearalenone metabolites were most commonly detected mycotoxins, followed by aflatoxins, roquefortine C and mycophenolic acid. The presence of mycotoxins was found to positively correlate with oxidative stress markers. The obtained results illustrate the importance of mycotoxin biomonitoring studies in humans and the need to elucidate the underlying mechanisms of mycotoxin-induced toxicity. Full article
(This article belongs to the Special Issue Biomonitoring of Mycotoxins)
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Article
Biomonitoring of Multiple Mycotoxins in Urine by GC–MS/MS: A Pilot Study on Patients with Esophageal Cancer in Golestan Province, Northeastern Iran
Toxins 2021, 13(4), 243; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13040243 - 29 Mar 2021
Viewed by 578
Abstract
A pilot study to investigate the occurrence of 10 mycotoxins (deoxynivalenol, DON; 3-acetyldeoxynivalenol, 3-ADON; 15-acetyldeoxynivalenol, 15-ADON; fusarenon-X, FUS-X; diacetoxyscirpenol, DAS; nivalenol, NIV; neosolaniol, NEO; zearalenone, ZON; zearalanone, ZAN; T-2 toxin, T-2; and HT-2 toxin, HT-2) in esophageal cancer patients was performed with the [...] Read more.
A pilot study to investigate the occurrence of 10 mycotoxins (deoxynivalenol, DON; 3-acetyldeoxynivalenol, 3-ADON; 15-acetyldeoxynivalenol, 15-ADON; fusarenon-X, FUS-X; diacetoxyscirpenol, DAS; nivalenol, NIV; neosolaniol, NEO; zearalenone, ZON; zearalanone, ZAN; T-2 toxin, T-2; and HT-2 toxin, HT-2) in esophageal cancer patients was performed with the urinary biomarkers approach in Golestan, Iran. Urine multimycotoxin analysis was performed by dispersive liquid–liquid microextraction and gas chromatography–tandem mass spectrometry (GC–MS/MS) analysis, and values were normalized with urinary creatinine (μg/g). Four mycotoxins, namely NEO (40%), HT-2 (17.6%), DON (10%), and HT-2 (5.8%), were detected in the analyzed urine samples. DON was only detected in the control group (5.09 μg/g creatinine), while T-2 (44.70 μg/g creatinine) was only present in the esophageal cancer group. NEO and HT-2 were quantified in both control and case groups, showing average of positive samples of 9.09 and 10.45 μg/g creatinine for NEO and 16.81 and 29.09 μg/g creatinine for HT-2, respectively. Mycotoxin co-occurrence was observed in three samples as binary (NEO/HT-2 and T-2/HT-2) and ternary (DON/NEO/HT-2) combinations, reaching total concentrations of 44.58, 79.13, and 30.04 µg/g creatinine, respectively. Further investigations are needed to explore a causal association between mycotoxin contamination and esophageal cancer. For this pilot study in Golestan, the low sample size was a very limiting factor. Full article
(This article belongs to the Special Issue Biomonitoring of Mycotoxins)
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Article
Assessment of Exposure to Mycotoxins in Spanish Children through the Analysis of Their Levels in Plasma Samples
Toxins 2021, 13(2), 150; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13020150 - 15 Feb 2021
Cited by 2 | Viewed by 621
Abstract
In this study, we present, for the first time in Spain, the levels of 19 mycotoxins in plasma samples from healthy and sick children (digestive, autism spectrum (ASD), and attention deficit hyperactivity (ADHD) disorders) (n = 79, aged 2–16). The samples were [...] Read more.
In this study, we present, for the first time in Spain, the levels of 19 mycotoxins in plasma samples from healthy and sick children (digestive, autism spectrum (ASD), and attention deficit hyperactivity (ADHD) disorders) (n = 79, aged 2–16). The samples were analyzed by liquid chromatography-mass spectrometry (triple quadrupole) (LC-MS/MS). To detect Phase II metabolites, the samples were reanalyzed after pre-treatment with β-glucuronidase/arylsulfatase. The most prevalent mycotoxin was ochratoxin A (OTA) in all groups of children, before and after enzyme treatment. In healthy children, the incidence of OTA was 92.5% in both cases and higher than in sick children before (36.7% in digestive disorders, 50% in ASD, and 14.3% in ADHD) and also after the enzymatic treatment (76.6 % in digestive disorders, 50% in ASD, and 85.7% in ADHD). OTA levels increased in over 40% of healthy children after enzymatic treatment, and this increase in incidence and levels was also observed in all sick children. This suggests the presence of OTA conjugates in plasma. In addition, differences in OTA metabolism may be assumed. OTA levels are higher in healthy children, even after enzymatic treatment (mean OTA value for healthy children 3.29 ng/mL, 1.90 ng/mL for digestive disorders, 1.90 ng/mL for ASD, and 0.82 ng/mL for ADHD). Ochratoxin B appears only in the samples of healthy children with a low incidence (11.4%), always co-occurring with OTA. Sterigmatocystin (STER) was detected after enzymatic hydrolysis with a high incidence in all groups, especially in sick children (98.7% in healthy children and 100% in patients). This supports glucuronidation as a pathway for STER metabolism in children. Although other mycotoxins were studied (aflatoxins B1, B2, G1, G2, and M1; T-2 and HT-2 toxins; deoxynivalenol, deepoxy-deoxynivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol; zearalenone; nivalenol; fusarenon-X; neosolaniol; and diacetoxyscirpenol), they were not detected either before or after enzymatic treatment in any of the groups of children. In conclusion, OTA and STER should be highly considered in the risk assessment of mycotoxins. Studies concerning their sources of exposure, toxicokinetics, and the relationship between plasma levels and toxic effects are of utmost importance in children. Full article
(This article belongs to the Special Issue Biomonitoring of Mycotoxins)
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Article
Presence of 19 Mycotoxins in Human Plasma in a Region of Northern Spain
Toxins 2020, 12(12), 750; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12120750 - 27 Nov 2020
Cited by 3 | Viewed by 636
Abstract
This study was conducted to investigate human exposure to 19 compounds (mycotoxins and their metabolites) in plasma samples from healthy adults (n = 438, aged 19–68 years) from Navarra, a region of northern Spain. Samples were analyzed by LC-MS/MS, before and after enzymatic [...] Read more.
This study was conducted to investigate human exposure to 19 compounds (mycotoxins and their metabolites) in plasma samples from healthy adults (n = 438, aged 19–68 years) from Navarra, a region of northern Spain. Samples were analyzed by LC-MS/MS, before and after enzymatic hydrolysis for the detection of possible glucuronides and/or sulfates (Phase II metabolites). The most prevalent mycotoxin was ochratoxin A (OTA), with an incidence of 97.3%. Positive samples were in the concentration range of 0.4 ng/mL to 45.7 ng/mL. After enzymatic treatment, OTA levels increased in a percentage of individuals, which may indicate the presence of OTA-conjugates. Regarding ochratoxin B, it has also been detected (10% of the samples), and its presence may be related to human metabolism of OTA. Sterigmatocystin was detected with a high incidence (85.8%), but only after enzymatic hydrolysis, supporting glucuronidation as a pathway of its metabolism in humans. None of the other studied mycotoxins (aflatoxins B1, B2, G1, G2 and M1; T-2 and HT-2 toxins; deoxynivalenol, deepoxy-deoxynivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol; zearalenone; nivalenol; fusarenon-X; neosolaniol; and diacetoxyscirpenol) were detected in any of the samples, neither before nor after enzymatic treatment. To the best of our knowledge, this is the first report carried out in Spain to determine the exposure of the population to mycotoxins and some of their metabolites using plasma, and the obtained results justify the need for human biomonitoring and metabolism studies on mycotoxins. Full article
(This article belongs to the Special Issue Biomonitoring of Mycotoxins)
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Article
Biomonitoring of Aflatoxin B1 and Deoxynivalenol in a Rural Pakistan Population Using Ultra-Sensitive LC-MS/MS Method
Toxins 2020, 12(9), 591; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12090591 - 12 Sep 2020
Viewed by 2354
Abstract
There are limited data on exposure to mycotoxins in Pakistan. Here, we measured exposure to deoxynivalenol (DON), a common contaminant of wheat, and aflatoxin B1 (AFB1), a known contaminant of rice, using biomarkers of exposure. Wheat (n = 195) [...] Read more.
There are limited data on exposure to mycotoxins in Pakistan. Here, we measured exposure to deoxynivalenol (DON), a common contaminant of wheat, and aflatoxin B1 (AFB1), a known contaminant of rice, using biomarkers of exposure. Wheat (n = 195) and rice (n = 62) samples were analyzed for AFB1 and DON levels, and the corresponding urinary biomarkers were analyzed in urine samples from a rural population (n = 264, aged 4–80 years, male 58%) using ultra-sensitive liquid chromatography–tandem mass spectrometry. AFB1 was detected in 66% of rice (5.04 ± 11.94 µg/kg) and 3% of wheat samples. AFM1 (hydroxylated form of AFB1) was detected in 69% of urine samples, mean 0.023 ± 0.048 ng/mL and DON was detected in 20% of urine samples, mean 0.170 ± 0.129 ng/mL. The maximum probable daily intake for DON derived from the urinary biomarker was 59.8 ng/kg b.w./day, which is below the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives’ tolerable daily intake (1000 ng/kg b.w./day). However, for aflatoxin, the derived margin of exposure (MoE) of (13.2) was well below the safe MoE (10,000) suggested by the European Food Safety Authority. The calculated aflatoxin-associated cancer risk of 0.514/105 individuals/year suggests that measures should be taken to reduce the AFB1 contamination in food, particularly rice, in Pakistan. Full article
(This article belongs to the Special Issue Biomonitoring of Mycotoxins)
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Review

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Review
Development and Limitations of Exposure Biomarkers to Dietary Contaminants Mycotoxins
Toxins 2021, 13(5), 314; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13050314 - 28 Apr 2021
Viewed by 804
Abstract
Mycotoxins are toxic secondary fungal metabolites that frequently contaminate cereal crops globally, presenting exposure hazards to humans and livestock in many settings. The heterogeneous distribution of mycotoxins in food restricts the usefulness of food sampling and intake estimates for epidemiological studies, making validated [...] Read more.
Mycotoxins are toxic secondary fungal metabolites that frequently contaminate cereal crops globally, presenting exposure hazards to humans and livestock in many settings. The heterogeneous distribution of mycotoxins in food restricts the usefulness of food sampling and intake estimates for epidemiological studies, making validated exposure biomarkers better tools for informing epidemiological investigations. While biomarkers of exposure have served important roles for understanding the public health impact of mycotoxins such as aflatoxins (AF), the science of biomarkers must continue advancing to allow for better understanding of mycotoxins’ roles in the etiology of disease and the effectiveness of mitigation strategies. This review will discuss mycotoxin biomarker development approaches over several decades for four toxins of significant public health concerns, AFs, fumonisins (FB), deoxynivalenol (DON), and ochratoxin A (OTA). This review will also highlight some knowledge gaps, key needs and potential pitfalls in mycotoxin biomarker interpretation. Full article
(This article belongs to the Special Issue Biomonitoring of Mycotoxins)
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Review
Mycotoxins—Biomonitoring and Human Exposure
Toxins 2021, 13(2), 113; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13020113 - 03 Feb 2021
Cited by 3 | Viewed by 739
Abstract
Mycotoxins are secondary metabolites produced by fungal species that commonly have a toxic effect on human and animal health. Different foodstuff can be contaminated and are considered the major source of human exposure to mycotoxins, but occupational and environmental exposure can also significantly [...] Read more.
Mycotoxins are secondary metabolites produced by fungal species that commonly have a toxic effect on human and animal health. Different foodstuff can be contaminated and are considered the major source of human exposure to mycotoxins, but occupational and environmental exposure can also significantly contribute to this problem. This review aims to provide a short overview of the occurrence of toxigenic fungi and regulated mycotoxins in foods and workplaces, following the current literature and data presented in scientific papers. Biomonitoring of mycotoxins in plasma, serum, urine, and blood samples has become a common method for determining the exposure to different mycotoxins. Novel techniques are more and more precise and accurate and are aiming toward the simultaneous determination of multiple mycotoxins in one analysis. Application of liquid chromatography (LC) methodologies, coupled with tandem mass spectrometry (MS/MS) or high-resolution mass spectrometry (HRMS) has become a common and most reliable method for determining the exposure to mycotoxins. Numerous references confirm the importance of mycotoxin biomonitoring to assess the exposure for humans and animals. The objectives of this paper were to review the general approaches to biomonitoring of different mycotoxins and the occurrence of toxigenic fungi and their mycotoxins, using recent literature sources. Full article
(This article belongs to the Special Issue Biomonitoring of Mycotoxins)
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