Implications of Mycotoxins in Food Safety

Abstract

The chapter aims to address an overview of the implications of mycotoxins in food safety and the presence of mycotoxins in various foods. Nowadays, everyone wants safe food with a long shelf life. Food safety has become a major strategic issue worldwide and has attracted worldwide attention. Mycotoxins are widely found in food and feed, and dietary exposure to them can induce various types of adverse health effects in humans and animals. Contamination of food by fungi and mycotoxins results in loss of dry matter, quality and nutrition, and poses a significant danger to the food chain. Moreover, mycotoxin contamination decreases product quality and reduces export values, which can lead to significant economic losses for producing countries. Mycotoxin contamination directly reduces food availability and has its own contribution to hunger and malnutrition, and the consumption of food contaminated with mycotoxins has major repercussions on human health.

1. Introduction

Food security is the basis of human health and quality of life. Today, food safety has become a major strategic issue in the world and has attracted worldwide attention [1].

Food security is effectively realized when food pillars, including food availability, access to food, food use, and food stability are at levels that allow all people to have physical and economical access to affordable, safe, and nutritious food to meet the requirement for a living active and healthy. When one of these four pillars weakens, then a society undermines its food security [2].

Most countries have established laws and regulations to provide the population with safe food. A safe food according to the law is nontoxic, harmless, and in accordance with nutritional requirements. It will not cause an acute, chronic, and potential danger to human health, for example, during planting, breeding, processing, packaging, storage, transport, sales, consumption, and other food activities. According to mandatory standards and requirements, there should be no foods with potential harm or danger to human health, such as harmful or poisonous substances with hidden potential to cause harm to consumers, which can lead to death [3].

Even though we have so much information at our disposal, the situation regarding global food security is still grim. Worldwide, food security and safety issues have increased over the past two decades. These increases continually raise questions about whether these current regulatory and control systems are effective. Recently, the World Health Organization (WHO), the Codex Alimentarius Commission (CAC), and other organizations have developed new limits for the safety of the international food trade [3].

Food safety and quality are greatly influenced by the living conditions of pollution in different countries, as well as their economic development. Given the rapid socioeconomic changes of the last decade, worldwide, which promise a flourishing economic rise, food processing, food supply, and consumption patterns have undergone significant changes, increasing the number of outbreaks of food security problems. One of these problems, present worldwide, is given by mycotoxins [3].

Mycotoxins are one of the most important contributing factors to food loss, especially in developing countries, and have become a recurring challenge for food safety [4]. As a result, to date, serious concerns are raised by both consumers and health and nutrition professionals about the presence of mycotoxins in food [5]. Contamination of food by fungi and mycotoxins results in loss of dry matter, quality and nutrition, and poses a significant danger to the food chain [6].

Moreover, mycotoxin contamination decreases product quality and reduces export values, which can lead to significant economic losses for producing countries. Mycotoxin contamination directly reduces food availability and has its own contribution to hunger and malnutrition [4]. Drought stress, failure to implement good agricultural practices, poor postharvest practices, and insect infestation are factors that influence mycotoxin contamination [7, 8].

In addition, socio-economic factors, such as poor transport and trading systems, lack of awareness, and insufficient regulations and legislation, can also contribute to the risks of mycotoxin contamination [4].

Mycotoxin contamination can be mitigated to acceptable levels through an integrated management approach along value chains [2] good agricultural practices, biological control, sorting, electromagnetic radiation treatments, ozone fumigation, chemical control agents [2] plant growth [9], good manufacturing practices, Hazard Analysis Critical Control Point (HACCP), and others [4] are some of the methods used to reduce/prevent the risks of mycotoxin contamination.

Contamination of food and food by mycotoxins has a considerable impact on food insecurity, trade, economy, and public health [10].

Food safety and security are basic needs for consumers. The major goal of world organizations is to take action to ensure food safety and security. In addition to food, the consumer is also exposed to water through oral intake, to the environment through inhalation, and exposure of the skin and penetration through it. Consumption of foods contaminated with mycotoxins, mainly cereals and foods of animal origin, is the most important and common route of exposure. Mycotoxins found in animal feed can indeed be transported in animal tissues, especially the liver, kidneys, and eggs [11].

2. Generalities. short classification of the main mycotoxins involved in food safety

Mycotoxins contribute significantly to food loss in developing countries [2]. According to the Food and Agriculture Organization (FAO), about a third of total food is lost, totaling about 1.3 billion tons per year. It is also estimated that approximately five billion people worldwide are exposed to mycotoxins, such as aflatoxins. However, formulas for assessing the global economic impact of the presence of mycotoxins in food have been extremely difficult to develop [12]. Mycotoxins are a global public health problem, with spices, crops, meat, and dairy products being the main sources of mycotoxins [13].

The economic and social impact of these mycotoxins includes losses caused by death and disease of humans and animals, veterinary and medical costs, reduced animal productivity, loss of livelihoods, control measures, economic losses for farmers through food and feed losses, and waste due to contamination. The negative effects of mycotoxin exposure could be mitigated through the use of agricultural knowledge and public health practices, such as proper processing and storage of products [2, 12].

The problem of mycotoxins is of paramount importance because it can have carcinogenic, immunological, allergenic effects [14], toxigenic, nephrotoxic, hepatotoxic, immunosuppressive, mutagenic [15], estrogenic and teratogenic effects, depending on exposure levels [16], which are particularly relevant for human consumption of contaminated food [14].

Mycotoxins are secondary fungal metabolites, not essential for the normal growth and reproduction of a fungus, but capable of causing biochemical, physiological, and pathological changes in many species and pose a global threat to public health. Mycotoxins have harmful effects on both humans and animals. These effects include immune toxicity, carcinogenicity, neurotoxicity, teratogenicity, nephrotoxicity, indigestion, hepatotoxicity, developmental and reproductive toxicity, and more. Most mycotoxins can be found in various agricultural products, which are then processed, staple foods and often consumed, which are generally dependent on their composition—food matrix composition, water activity, relative humidity and moisture content of the product, pH, temperature, physical appearance, and degree of damage, as well as the presence of mold spores [17].

Mycotoxins are secondary metabolites toxic to humans and animals [16, 18]. Most of these toxins have relatively low molecular weights and are generally thermally stable demonstrating high levels of bioaccumulation [16, 19]. More than 400 types of mycotoxins have been identified, however, only about 10–15 are considered to be of public health interest [19], with aflatoxin (AF), deoxynivalenol (DON), ergot alkaloids, fumonisins (FB), ochratoxin A (OTA), patulin (PAT), zearalenone (ZEN), and trichothecenes (T-2 and HT-2), the most prominent due to their high incidence in food. OTA and AF can be produced by toxigenic fungi associated with dried meat products [2, 12, 16].

2.1 Aflatoxins (AF)

Aflatoxins (A-flavus-toxins) are considered the best known and most toxic mycotoxins. They are produced by certain species of molds of the genus Aspergillus, their growth being thus particularly favored at temperatures between 26°C and 38°C and with a moisture content of more than 18%. Six forms of aflatoxins are identified—aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1), aflatoxin G2 (AFG2), aflatoxin M1 (AFM1), and aflatoxin M2 (AFM2). They are reported in several crops, mainly maize, peanuts, pistachios, and cotton seeds. Aspergillus flavus is responsible for the production of aflatoxins B1 and B2, while Aspergillus parasiticus can produce aflatoxins B1, B2, G1, and G2, especially in storage time [17, 20, 21].

Aflatoxin B1 (AFB1) is considered the most potent natural carcinogen and is classified by the International Agency for Research on Cancer (IARC) group 1 as carcinogenic to humans. It is estimated that AFB1 causes up to 28% of all liver cancers, and has been associated with impaired immune system growth and dysfunction. AFB1 and its metabolites are excreted in urine, feces, and breast milk [22, 23].

Aflatoxins contamination has been demonstrated in cereals and cereal-based products [24, 25], organs, meat, pork products, and chicken eggs [26, 27]. In addition, aflatoxin M1 is released into milk through the milk glands of cattle fed aflatoxin B1—contaminated feed. Given the stability of the toxin during pasteurization and sterilization of milk and dairy products, even a relatively small amount of aflatoxin M1 can significantly affect human health [28].

2.2 Ochratoxins

The ochratoxin group includes ochratoxins A, B, C, and TA. An ochratoxin molecule is composed of dihydroisocoumarin and the L-β-phenylalanine component. The most toxic representative of the group is ochratoxin A (OTA), isolated from the mold of Aspergillus ochraceus [29].

The researchers’ reports showed that the genus Penicillium (P. verrucosum) and members of Aspergillus (A. carbonarius and A. ochraceus) are the main producers of the toxin. This toxin can be produced over a wide range of conditions in terms of humidity and temperature, the optimum humidity of crops, for its synthesis, is at least 16%, and the optimum temperatures are between 20 and 25°C [30].

Significant concentrations of ochratoxin A have been found in plant-based foods, such as wheat, corn, rye flower, buckwheat, and breakfast cereals, but the toxin can also be found in offal, meat, and meat products due to secondary contamination [31]. Sources in the literature have reported that the most substantial amounts of ochratoxin A can be found in organ-based meat products [32, 33]. In addition, significant amounts of this mycotoxin have been found in smoked meat products and other animal products [17, 31].

2.3 Zearalenone (ZEN)

The toxin F-2, the mycotoxin zearalenone, received this designation in 1962, after the Giberella zeae mold, from which it was isolated. The most important producers of zearalenone are the forms—Fusarium graminearum, Fusarium culmorum, Fusarium moniliforme, Fusarium roseum, and Fusarium tricinctum [17].

This mycotoxin is a nonsteroidal estrogen, and its chemical structure is that of resorcylic acid lactone [34]. Zearalenone production is increased especially in wetter, somewhat colder climates, with temperatures of 10–15°C. More than 150 zearalenone derivatives are currently known. The most toxic is considered α-zearalenone. More toxins up to 3–4 times compared to zearalenone. β-Zearalenone is thought to have an activity similar to that of zearalenone. This mycotoxin is thermally stable and stable in several types of solvents, such as ethyl acetate, acetonitrile, acetone, methanol, or chloroform. Zearalenone is insoluble in water but can be dissolved in alkaline water, alcohols, or ether. It is also insoluble in carbon tetrachloride and carbon [17].

Cold wet periods and the early onset of frost, followed by strong periods of sunshine, favor the infestation of crops with Fusarium spp. Before harvest, in this process, zearalenone is also produced [30].

It is commonly found in corn, but can also be found in wheat, barley, sorghum, and rye from countries around the world. Although at much lower concentrations, zearalenone has also been found in milk, meat, organs, and eggs from animals exposed to this mycotoxin through contaminated feed [17].

2.4 Fumonisins (FB)

Fumonisins are the group of mycotoxins produced by molds of the genus Fusarium and comprise fumonisins B1, B2, B3, and B4. The most toxic of these, fumonisin B1, is a propane-1,2,3-tricarboxylic acid diester. Molds that produce fumonisins in significant amounts are Fusarium verticillioides, Fusarium proliferatum, and Fusarium moniliforme. They are soluble in water, acetonitrile and methanol, thermally stable, and resistant to alkalis that are not photosensitive. The high temperatures used in food processing do not affect their stability.

Substantial amounts of this mycotoxin have been identified in foods intended for the human diet, but also in milk, meat, and eggs of animals feeding on feed contaminated with fumonisin B1, even if they were not found in concentrations harmful to human health. Recently, fumonisins B2 and B4 were produced by Aspergillus niger isolated from coffee and fumonisin B2 in A. niger from grapes. Fumonisin B2 is detected in coffee beans, wine, and beer [17, 35, 36].

Data from the literature have shown correlations between different diseases such as liver cancer in rats, esophageal cancer in humans, leukoencephalomalacia in horses or donkeys, pulmonary edema in pigs, and contamination with fumonisins. Fumonisin B1, according to IARC, is classified in group 2B as a potential carcinogen for humans [17, 36].

2.5 Deoxynivalenol (DON)

Deoxynivalenol (DON, vomitoxin), is a tetracyclic epoxy sesquiterpene and belongs to the group of trichothecene mycotoxins type B [37] and was first isolated from damaged barley grains in 1972. DON production is mainly attributed to molds Fusarium graminerarum and Fusarium culmorum and is enhanced by wetter climates (water activity of 0.97) at temperatures of 25–28°C [17]. DON is a small colorless powder that is soluble in polar solvents, such as water, methanol, ethanol, acetonitrile, and ethyl acetate. It remains stable during storage, grinding, and processing and is, at least to some extent, resistant to heat processing of both food and feed [38].

Among trichothecans, DON is the least toxic, but it is gaining importance due to its high prevalence in food around the globe. The man, who consumes contaminated grains, accuses acute nausea, vomiting, diarrhea, abdominal pain, headache, dizziness, and fever. In animals, acute exposure to DON leads to lower food intake (anorexia) and vomiting, while prolonged exposure may lead to lower yields and thymus, spleen, heart, and liver disease.

The main grains in which DON has been identified are wheat, corn, rye, oats, and barley. They are found, but less often in rice, triticale, or sorghum. Cereals can be contaminated with DON in the field, but also during storage. Consequently, deoxynivalenol can be found in the raw material, the finished food product based on cereals, but also in feed [39]. It has been suggested that DON may also be present in products of animal origin, such as meat and milk [40]. Its metabolites are rapidly excreted from the body, especially in urine, but also in milk, however, in much lower concentrations [17].

2.6 Patulin (PAT)

Molds of the genera Aspergillus, Byssochlamys, and Penicillium are responsible for the production of the mycotoxin patulin. It can be grown on cereals, fruits, vegetables, processed foods, or on different types of cheese. Penicillium expansum is the mold that produces this toxin; it is generally found in the soil and is the most important source of fruit patulin. Patulin, in terms of chemical composition, is a polyketide lactone, made up of a single small molecule. This molecule can be isolated as white or colorless crystals. Patulin is soluble in water, ethanol, methanol, acetone, or ethyl acetate/amyl. Patulin is less soluble in benzene or diethyl ether. This mycotoxin is stable in acidic solutions, but its sulfuric acid can degrade.

Once produced by the mold Penicillium expansum, the patulin most often reveals its presence in the form of a disease that affects apples after harvest (rot, rot) or during storage. This mycotoxin has been identified in apples, apple juice, pears, grapes, fodder, and flowers affected by brown rot. Given that consumers, but also producers tend to eliminate the rotten part of fruits or cereals before consumption or processing, the maximum allowed limit for food safety is not exceeded. In the case of cheese, cysteine in high concentrations interacts with patulin and deactivates it. In addition, it has been reported that patulin can be annihilated by fermentation and is, therefore, absent in fruit-based alcoholic beverages and fruit juice-based vinegar, but is present in apple wine (cider). Heat processing manages to moderately reduce the level of patulin; therefore, the patulin found in apple juice maintains its presence during the pasteurization process [17, 41].

2.7 Trichothecenes (T-2 and its main metabolite HT-2)

T-2 toxin together with HT-2, the most important metabolite in or, are produced by molds of the genus Fusarium and are trichothecene type A toxins. This mycotoxin is the basic representative of trichothecine, present in most situations when we talk about trichothecine. It was first identified in maize grown in France. It is a natural sesquiterpene and was isolated from the mold Fusarium tricinctum. After several studies, it was concluded that the T-2 toxin can be produced by several species of the genus Fusarium, such as Fusarium sporotrichioides, Fusarium langsethiae, and Fusarium poae.

The optimal parameters for the development of this mycotoxin are at least 0.88 water activity and a temperature below 15°C, but can be produced between −2°C and 32°C [27, 42]. T-2 toxin is thought to be a powerful cytotoxin and immunosuppressant capable of causing acute intoxication and chronic disease in both humans and animals. Symptoms of acute intoxication include nausea, tremors, abdominal pain, diarrhea, and weight loss [17]. T-2 toxin inhibits protein synthesis, leading to side effects of DNA and RNA synthesis [27]. In addition, it has an adverse effect on the immune system, showing changes in the number of leukocytes and hypersensitivity [42].

Of all cereals, oats are the ones in which contamination with this mycotoxin occurs most frequently and in higher concentrations. Residues and metabolites of T-2 toxin have been found in milk, but not in significantly high concentrations [17, 43].

2.8 Ergot alkaloids

Ergot alkaloids are produced by multiple species of the genus Claviceps. Claviceps purpurea is the basic representative of the genus and is the most common in Europe. The most affected cereals are generally rye, wheat, oats, barley, triticale, and millet. Rye is the cereal where this fungus forms sclerotia (dark crescent-shaped bodies that describe the last stage of evolution of plant disease). Pure ergot alkaloids form colorless crystals soluble in organic solvents, such as acetonitrile and methanol, but also in mixtures of organic solvents and buffers. Some of the ergot alkaloids, especially those belonging to the group of simple lysergic acid derivatives, as well as ergoclavins, are soluble in water only to a certain extent. To the extent that more than 50 ergot alkaloids have been isolated from fungal sclerotia, attention has been paid to ergometrine, ergotamine, ergosine, ergocristine, ergocryptine (the latter being a mixture of α- and β-isomers), ergocornine, and their correspondent.

Many mass poisonings caused by the consumption of cereals, flowers, and bread contaminated with ergot alkaloids are recorded throughout human history. If contaminated cereals are consumed in small quantities, one can only expect indigestion, while higher consumption leads to ergotism, that is, the disease that manifests itself with hallucinations, pain, and severe vasoconstriction eventually leading to dry gangrene and numbness of the limbs. The worst-case scenario involves kidney and heart failure and fatal outcomes, while abortion can be induced in pregnant women. A close link between sclerotia content and ergot alkaloid levels has been established in different crops (barley, oats, rye, triticale, and wheat grains) [17, 44].

2.9 Beauvericin—BEA

Beauvericin is a cyclic hexadepsipeptide that is synthesized by various toxigenic fungi, including several species of Fusarium [45]. BEA can be produced by different species of Fusarium in different regions. For example, in the USA and South Africa, F. circinatum is the most important BEA-producing fungus, while in Europe, F. sambucinum and F. subglutinans are the most relevant [46]. As a mycotoxin, BEA is a relevant natural contaminant when referring to mycotoxins in cereals and cereal-based products [47]. BEA contamination is a reported food safety problem in Southern Europe [48]. BEA is toxic to human tissues and cells and has a cytotoxic effect at a lower concentration than that for aflatoxin B1 [49, 50].

2.10 α-Cyclopiazonic acid—CPA

Cyclopiazonic mycotoxin was first discovered in 1968. The species responsible for CPA production are Aspergillus (A. tamarii, A. oryzae, and A. flavus) and Penicillium (P. dipodomyicola, P. camemberti, P. griseofulvum, and P. commune). This mycotoxin has been reported in foods such as milk and cheese, oilseeds and nuts, cereals, dried figs, and meat products and has a toxicological effect. It was most commonly detected in products such as peanuts and corn. CPA is toxic to animals such as rats, pigs, guinea pigs, poultry, and dogs. After ingestion of feed contaminated with CPA, the tested animals show severe gastrointestinal disorders and neurological disorders. The affected organs were the liver, kidneys, heart, and digestive tract, which show degenerative changes and necrosis [23].

2.11 Citrinin—CIT

Citrinin is a polyketide mycotoxin, which contaminates food and is associated with various toxic effects. CIT is produced by several fungal strains belonging to the genera Penicillium, Aspergillus, and Monascus and is usually found together with another nephrotoxic mycotoxin, ochratoxin A. Although, it is clear that exposure to CIT can have toxic effects on the heart, liver, kidneys, and the reproductive system, the mechanism of CIT-induced toxicity remains largely elusive. The presence of CIT has been reported in fruits, fruit juices, beans, vegetables, red rice, herbs, spices, and spoiled dairy products [51].

2.12 Enniatin—ENN

Enniatins are a group of cyclic hexadepsipeptides, comprising 29 enniatin analogs, belonging to groups A and B. Of these analogs, the most commonly found in food (most commonly found in cereals and cereal products) and feed are A, A1, B, B1, although Enniatins B2, B3, and B4 are also found, especially in cereals. This heterogeneous group of mycotoxins is produced by several types of fungi belonging to the genus Fusarium—F. acuminatum, F. avenaceum, F. oxysporum, F. poae, F. sporotrichioides, F. sambucinum, and F. tricinctum [52, 53].

2.13 Alternaria toxins—ATs

Alternaria is one of the main mycotoxins with a mycotoxigenic effect found in cereals around the world. Although, cereals are constantly affected by Alternaria spp. and their toxins, little relevance is still given to the subject. Currently, tenuazonic acid in sorghum/millet baby foods is the only Alternaria toxin regulated by a government official (the Bavarian Food and Safety Authority) [54].

3. Mycotoxins identified in food

Mycotoxins are not only highly toxic but also widely distributed in various products, such as cereals [55, 56], nuts [57, 58], fruits, vegetables [59], corn [60], seaweed [61], wines [62], meat [12], eggs [63], dried fruits [64], coffee [65], milk [66], and so on. The Food and Agriculture Organization (FAO) has estimated that approximately 25% of world food crops are contaminated with mycotoxins each year [10].

Consumption of foods contaminated with mycotoxins could be the most important source of exposure to toxic mycotoxins, which can be mainly dangerous especially for children and infants [67]. Obviously, a wide mass of mycotoxins can be found in the same product, because a single species of fungus can produce several toxic metabolites, even several species of fungi can be present simultaneously and can produce different toxins [56]. For example, raw cereals are often contaminated with DON and NIV, and other mycotoxins such as AF, ZEN, and OTA are also detected in low-level raw cereals [68]. In addition, DON and ZEN are widespread especially in rice, and mycotoxins such as AF, OTA, and FB1 are also detected in rice [69]. Although mycotoxins are frequently coexisting, different samples may contain only the most common individual mycotoxin. For example, the most common mycotoxin in milk is AFM1, which is also known as “milk toxin.” Most investigations are aimed at detecting AFM1 in milk [70]. PAT is usually predominant in fruit-derived products [71]. In addition, the most common mycotoxin in wine is OTA [72]. Migration and environmental accumulation are the other important ways of exposure for people, with the exception of direct input. For example, Schenzel et al. reported that 3-acetyldeoxynivalenol, DON, NIV, and BEA were detected in Swiss Midland Rivers [73]. A number of researchers have also indicated that drinking water is an important matrix contaminated with mycotoxins [74] and the living environment of humans, these being a principal threat to public health.

The increasing spread of mycotoxins and the highly toxic effects have led to the establishment of organizations that aim to make regulations on the control of food contamination. For example, the FAO a scientific advisory board of the WHO and the Joint Committee of Experts on Food Additives (JECFA) have the responsibility to assess the risks of mycotoxins. In 2001, the Commission’s Scientific Committee for Food (SCF) initially set maximum levels for AF, OTA, and PAT in food (EU Regulation 466/2001) (EC, 2001). In addition, the IARC has classified mycotoxins into different categories according to human carcinogenic risk. In addition, the EC has set the maximum levels allowed for most mycotoxins in food by Commission Regulation No. EC 1881/2006, but also methods of sampling and analysis for their control with the help of EC 401/2006 to protect or reduce losses that occur in production and to protect human health. The EC has set maximum limits of 0.012 mg/kg for AFB1 in apricots, pistachios, and almonds; 0.00005 mg/kg for AFM1 in raw or heat-treated milk and dairy products; 0.05 mg/kg for PAT in fruit juices; 0.002 mg/kg for OTA in wine; 0.075 mg/kg for ZEN in cereals; 0.5 mg/kg for DON in bread; 10 mg/kg for the amount of AFG1, AFG2, AFB1, and AFB2 in nuts and peanuts; and maximum limits of 400 μg/kg for ZEN in refined maize germ oil [10].

3.1 Mycotoxins in cereals

Cereals are perhaps the most consumed categories of products worldwide by humans because they are an important source of energy, vitamins, minerals, and fiber [75]. These products can come with different mushrooms from the farm, after harvest, or during storage. Most mycotoxins found in cereals are influenced by poor storage conditions, temperature, climate, drought, or insect damage [76]. The physicochemical composition of cereals, including water activity or pH, can influence the development of mycotoxins [58, 77].

3.2 Mycotoxins in wheat

Wheat contributes to a wide range of bakery products, such as bread, breakfast cereals, biscuits, cakes, pasta, and other cereal-based products. Therefore, the level of contamination of wheat with mycotoxins is essential in the food and feed chain. According to existing studies on wheat seeds, the major occurrence of mycotoxins was DON, ZEN, AFB1, OTA, HT-2/T-2, AF, and FUM, respectively. According to the EC regulation, the recommended limit for wheat mycotoxins is 4 μg/kg for AF, 2 μg/kg for AFB1, 1250 μg/kg for DON, 5 μg/kg for OTA, and 100 μg/kg for ZEN [78].

Of the studies on mycotoxins in wheat grains, 16.6% were reported to exceed EU-recommended limits. The most common were AF with a percentage of 50%, of which 40% were AFB1, followed by ZEN WITH 22.2%. In the case of DON, the highest value, 17,753 μg/kg, was reported in China [79], and in the wheat samples from Qatar Hassan et al. reported DON values of 0.1 μg/kg [78]. For ZEN the highest values were reported in India [80], and the lowest values in Qatar [81]. In the case of AF the highest values, 9 μg/kg, were reported for wheat samples from Qatar [81], the maximum level allowed for the EU being 4 μg/kg, and in wheat samples from Greece AF was not detected [82].

Topi et al. analyzed 10 Fusarium toxins in 71 wheat samples in Albania. The analytical procedure consisted of simple one-step sample extraction, followed by the determination of toxins using liquid chromatography coupled with tandem mass spectrometry. Fusarium toxins were found in 23% of the wheat samples analyzed. In the wheat samples, the only Fusarium mycotoxin detected was deoxynivalenol (DON), present in 23% of the samples, with a concentration of 1916 g/kg, exceeding the maximum level allowed by the EU (1250 g/kg) [83].

According to Malir et al., the most common mycotoxins in wheat flour are aflatoxins B1, B2, G1, G2, ochratoxin A, and deoxynivalenol [84].

3.3 Mycotoxins in corn

Corn seeds are often contaminated with Fusarium verticillioides and Fusarium proliferatum that produce FUMs toxin. However, other mycotoxins have been found in corn along with FUMs [78]. The highest contamination rate was related to AFB1, ZEN, and DON, respectively. The European Commission (EC) has defined the maximum concentration of mycotoxins in maize. When maize is used for human consumption, these maximum quantities are 4000 μg/kg for FUMs, 1750 μg/kg for DON, 350 μg/kg for ZEN, 5 μg/kg for OTA, 2 μg/kg for AFB1, 10 μg/kg for AFs, and 100 μg/kg for T-2 + HT-2 [10]. In the study conducted by Aristil et al., 87.5% of the samples detected with AFB1, the AF level was higher than the allowed level. This value was 80%, 66.6% for AF and OTA, respectively. For other mycotoxins, the values ​​detected were often lower than the maximum EC values. Existing research has shown that the highest prevalence of AFB1 was in Haiti with 188 44 μg/kg [85], Kenya with 76.2 μg/kg [86], and Serbia with 44 μg/kg [87]. Kos et al. reported a high average prevalence of DON (963 μg/kg), ZEN (163 μg/kg) in Serbia [88]. The high OTA content (1662 μg/kg) is reported in Vietnam [89], and Skendi et al. in Greece reported the lowest OTA levels (0.7 μg/kg) [82]. According to studies by Bertuzzi et al. in Italy [85], the highest FUM content was 43,296 μg/kg [90]. Corn is used as a raw material for flour, breakfast cereals, popcorn, popcorn, and various other foods [78]. Consequently, maize is a good host for mycotoxins, such as AFB1, OTA, ZEN, and DON, and requires continuous monitoring. The presence of these mycotoxins represents a real danger for the entire food chain due to the high consumption of corn [91].

Topi et al. analyzed 10 Fusarium toxins in 45 maize samples from Albania. Fusarium toxins were found in 78% of the maize samples analyzed. In 76% of the corn samples, fumonisins B1 (FB1) and B2 (FB2) were found with concentrations between 59.9 and 16.970 g/kg. The amount of FB1 and FB2 exceeded the maximum level allowed by the EU (4000 g/kg) in 31% of the maize samples [83].

According to Zinedine et al., the most common mycotoxins in cornflakes and corn-based foods are fumonisins and beauvericin [92].

3.4 Mycotoxins in rice

The mycotoxins identified in rice seeds based on prevalence were AFB1, ZEN, DON, FUM, AF, OTA, and HT-2/T-2 toxins [78].

According to the maximum number of mycotoxins allowed by the EC for rice seeds, the following values ​​are given—4 μg/kg for AF, 2 μg/kg for AFB1, 5 μg/kg for OTA, 100 μg/kg for ZEN, and 1250 μg/kg for DON. Of the studies analyzed, exceedances of the EC standard limit for AF and AFB1 (50%), FUM (25%), DON (16.6%), ZEN (11.1%) were reported. Values exceeding the maximum limits allowed by the EU were also reported in a study conducted in Somalia, where 330 μg/kg AFB1 and 4361 μg/kg FUM were detected in the rice samples [93]. The level of FUM and HT-2/T-2 toxins in all rice samples was below the EU maximum. In China, the maximum allowable level for DON in rice samples is reported at 1607 μg/kg [78].

Several authors have reported that the most common mycotoxins in rice are total aflatoxins, aflatoxin B1, ochratoxin A, and beauvericin [94, 95].

3.5 Mycotoxins in barley, sorghum, oats, and rye

DON was an abundant mycotoxin in barley samples collected from different countries, followed by ZEN and T-2/HT-2 toxins. A study conducted in Canada showed that 56% of cold-season barley presented to the mycotoxin-contaminated industry whose DON concentration in some samples exceeded the regulatory level (1250 μg/kg) [96]. According to several studies conducted in Argentina [97], the Czech Republic [98], and Brazil [99], the main mycotoxin of the genus Fusarium reported in barley samples was DON. In a study conducted in Turkey, in the analyzed barley samples ZEN was not detected, and DON did not exceed the maximum level allowed by the EU (138–973 μg/kg) [100]. DON, FUMs, T-2/HT-2 reported in 50%, 25%, and 50% of barley samples from the Qatar food market with average values ​​of 0.048 mg/kg, 0.553 mg/kg, and 0.067 mg/kg [81].

The most common mycotoxins in sorghum are FUM, AFB1, and ZEN [101]. According to a study conducted in Togo, FUM was detected in 67% of the samples and AFB1 in 25% [102]. In another study conducted in Somalia, the maximum allowable limits for FUM (FB1 and FB2) and AFB1 were exceeded in the sorghum analysis samples [93]. In a study conducted in Tunisia, in the analyzed sorghum samples, the presence of mycotoxins AFB1, OTA, and ZEN was reported, with values between 0.03–31.7 μg/kg, 1.04–27.8 μg/kg, and 3.75–64, 52 μg/kg, respectively [103].

In a study conducted in Nigeria, all sorghum samples analyzed were contaminated with FUM and AF. OTAs have also been identified in some samples [104]. In a study conducted in Switzerland, on oats, by Schöneberg et al., the majority of mycotoxins identified were T-2/HT-2 [105]. In another study conducted in India, the analyzed oat samples were contaminated with ZE in the proportion of 84%, identifying values between 5.31 and 389 μg/kg [80]. In the US study by Jin et al., 75% of the rye samples were contaminated with DON, reporting values below 1.0 mg/kg, but showed an increase through the malting process [106].

According to Meca et al., the most common mycotoxins in barley are deoxynivalenol and beauvericin [107]. The most mycotoxins in cereal porridge are aflatoxins B1, B2, G1, G2 and deoxynivalenol and in breakfast cereals are aflatoxins B1, B2, G1, G2 [108].

3.6 Mycotoxins in fruits, vegetables, and preparations thereof

Fruits and vegetables are extremely sensitive to fungal infestation due to their high water content and abundance of nutrients. They can decompose at any stage of the growth, harvesting, and storage processes, resulting in the production and accumulation of various mycotoxins [109].

Previous work has shown that mycotoxins that contaminate fruits and vegetables mainly include the toxin Alternaria [110], OTA [111], PAT [109, 112], and trichothecenes [113].

Although consumers can cut the rotten parts of fruits and vegetables before consumption, several mycotoxins, especially those mentioned above, may be present in the rest of the parts [113, 114], indicating that the removal of rotten parts cannot completely eliminate mycotoxin contamination.

A study of 20 samples of sweet peppers from two varieties showed that mycotoxins from Fusarium species involved in the internal rot of fruit migrate from contaminated peppers to initially healthy peppers. B fumonisins (1, 2, and 3) and beauvericin were identified after 10 days of incubation in a closed container and 20°C sweet pepper temperature conditions. Fumonisins B (1, 2, and 3) have been identified in lesions and around the tissue, indicating their migration to healthy parts. The values identified were between 690 and 104,000 μg/kg in lesions for fumonisin B (1) and outside the maximum lesion 556 μg/kg. For the other fumonisins, lower values were obtained in the lesions—10,900 μg/kg for fumonisin B (2) and 1287 μg/kg for fumonisin B (3). In the case of beauvericin, it was identified only in lesions, in a proportion of 95%, with values between 67 and 73,800 μg/kg [114]. A similar study was conducted for the analysis of eight mycotoxins (Alternaria toxins, ochratoxin A, patulin, and citrinin) on apple fruits, sweet cherries, tomatoes, and oranges [113].

H. Dong et al. analyzed seven mycotoxins (AOH, AME, TeA, TEN, OTA, PAT, and DON) from cherry tomatoes and two green leafy plants (salad and pakchoi) provided by Food Science and Technology—Guangzhou Harmony, China, and strawberries and tomatoes were bought from the strawberry fields and markets located in Guangzhou, China. All samples were freshly collected and checked for intact and no rotten visible parts. Mycotoxins were not detected in any of the fresh samples. During long storage, TeA was identified for tomatoes and AME and AOH for strawberries. Increased concentrations were observed with storage time. Studies have shown that optimal storage conditions for fresh fruits and vegetables, which include proper packaging and low temperature, help, delay the formation of mycotoxins [59].

Fruits and pomegranate juice from Greek markets were studied by Myresiotis et al. Three Alternaria mycotoxins (alternariol, alternariol monomethyl ether, and tentoxin) were determined, and in fresh samples, they were not identified. However, in the case of artificial inoculation of pomegranate fruits with various species of Alternaria alternata, concentrations between 0.3 and 50.5 μg/g were detected, the tentoxin not being detected [111].

A larger study of pomegranate fruits in Greece and Cyprus was presented by Kanetis et al. The fruits were studied before and after harvest. The results show that the rot of pomegranate fruits before harvesting was mainly caused by species of the genera Aspergillus (Aspergillus niger and Aspergillus tubingensis) and Alternaria (A. alternata, Alternaria tenuissima, and Alternaria arborescens) [115].

And the postharvest fruit spoilage was mainly caused by Botrytis spp. and to a lesser extent by isolates of Pilidiella granati and Alternaria spp. Production of alternariol (AOH), alternative monomethyl ether (AME), and tentoxin (TEN) was estimated among Alternaria isolates, while production of OTA and fumonisin B2 (FB2) was assessed in identified black asparagus. In total, in both countries, 89% of Alternaria isolates produced AOH and AME in vitro, while TEN was produced by 43.9%. The data presented imply that the mycotoxin species Alternaria and Aspergillus not only constitute a significant subgroup of the fungal population associated with the rotting of pomegranate fruits responsible for fruit deterioration but also present a potential risk factor for the health of consumers of basic products of pomegranate [115].

Apples, represented by the varieties Fuji, Golden Delicious, Granny Smith, and Red Delicious, in the study conducted by Ntasiou et al. are most affected by mycotoxins—AOH, AME, and TEN [116]. According to Munitz et al. isolated mycotoxins with the potential to be present in blueberries are FB1, FB2, FB3, ZEA, DON, AOH, AME, AFB1, AFB2, AFG1, HT-2, and T-2 [117].

3.7 Mycotoxins in baby food

There is a growing interest in baby food. According to the study conducted by Sarubbi et al., patulin is detected very often in baby food in Italy. According to EC regulation 1881/06, the maximum permitted limit of patulin in baby food is 10 μg/kg or 10 μg/l. A total of 80 homogenized baby foods were analyzed to assess children’s exposure to patulin by consuming these products. Experimental tests revealed significant differences between products from organic production and those from traditional production in all categories analyzed. Tomato concentrates showed an average patulin concentration of 7.15 ng/ml of the product; tomato sauce for baby food of 5.23 ng/ml; tomato sauce 4.05 ng/ml; homogenized pear of 0.79 ng/ml, homogenized apple of 0.85 ng/ml. The low incidence of patulin, or low concentrations, in Italian products, is a quality parameter for fruits and their derivatives [112].

The most common mycotoxins in baby food and baby fruits are aflatoxins B1, B2, G1, G2 patulin, and beauvericin [84, 118].

3.8 Mycotoxins in spices

Abrunhosa et al. report the presence in the spice of several mycotoxins such as ochratoxin A, sum of aflatoxin B1, aflatoxin B2, aflatoxin G1, and aflatoxin G2 [119].

3.9 Mycotoxins in wine

Fungal diseases in the vineyard reduce the quality of grapes and affect their volatile profile. Therefore, it influences the taste, aroma, and color of both the juice and the wine. The most common mycotoxins in stubble are aflatoxins, alternariol, OTA, tenuazonic acid, citrinin, patulin, or fumonisin B2.

The countries that provide the most information about wine mycotoxins are the largest wine producers in Europe—France, Italy, and Spain. The most common and worrying mycotoxin in grapes is OTA, produced by Aspergillus carbonarius. The most important factors regarding the determination of the contamination once identified are the climate, the most important factor, and the high temperatures. The highest concentrations of OTA have been identified in southern Europe, where it is warmest. Accurate fungal identification and detection of mycotoxins in fungi are important and practical methods need to be considered. Both white and red wines, dry, sweet, or hardened can be contaminated with mycotoxins. According to reported studies, it seems that OTA appears more often in red and sweet wines, compared to white ones [120].

According to Oteiza et al. mycotoxins such as PAT and OTA were identified in fruit juices and wines collected in Argentina between 2005 and 2013. PATs were identified in 1997 from 5958 samples, with concentrations ranging from 3.0 to 19,622 μg/l, and 510 samples showed PAT levels above 50 μg/l. A total of 1401 with concentrations between 0.15 and 3.6 μg/l. These mycotoxins identified in fruit juices and wines are influenced by fruit type, product type, and year of production [62].

Jesus et al. in their study noticed that the most common mycotoxin in wines in the United States is OTA [121].

3.10 Mycotoxins in beer

Beer is the most consumed alcoholic beverage in the world. Its mycotoxin contamination is a public health concern, especially for heavy drinkers.

Many studies have been published on the fate of mycotoxins in beer production, analyzing the general production process or only part of it and highlighting the physical parameters that lead to variations in mycotoxin concentration [122, 123, 124].

Many studies on beer have focused their investigation on DON, which is the most abundant mycotoxin and is the biggest public health problem related to beer consumption [125].

According to EC regulation 1881/2006 and Commission Recommendation, 2013/165/EU, the maximum allowed levels of mycotoxins in the European Union for 13 compounds are regulated. In the case of beer, we refer to cereal products for which the following limits have been established—for AFB1—2 μg/kg, for total AF—4 μg/kg, for ZEN—75 μg/kg, for DON—750 μg/kg, for OTA—5 μg/kg, and for FUMB1 + FUMB2—400 μg/kg. These limits are considered of great importance because beer has high acceptability worldwide, is consumed in large quantities, and avoids the accumulation of mycotoxins, especially for loyal consumers. Mycotoxin contamination can occur at different stages of brewing. Some of them can be transferred from cereals to malt and then to beer due to their high thermal stability (AF, ZEN, and DON) and water solubility of mycotoxins (DON and FUM) [124, 126].

Whatever the origin, numerous surveys on the occurrence of mycotoxins in beer have been conducted worldwide to date, analyzing different styles of brewing. Many surveys of beer are specific to mycotoxin, looking for the appearance and exposure of humans to various Fusarium mycotoxins found in beer. Others are specific to the style of beer, grouping the beer samples according to the production style applied to the malted barley from which they are made [99, 126].

DON and its derivatives, together with AF, FB, ZEA, T-2, and HT-2 are the most studied mycotoxins in beer and barley, respectively. Among the technological processes, the most relevant stages in the beer production process that have an inhibitory effect on mycotoxins are soaking, baking, mixing, fermentation, and clarification. In these stages, mycotoxins are removed with drainage water, used grain and fermentation residues, diluted or destroyed as a result of heat treatment, or adsorbed on the surface.

Germination has no effect on the level of DON in beer but promotes its transformation into its glycosylated derivative (DON-3-Glc). During mixing, enzymes not only stimulate the release of conjugated DON from protein structures but also decrease the initial toxin concentration due to dilution. This step can be a source of contamination with AF and FUM due to corn-free malt adjuvants that are used for the purpose of high levels of fermentable sugars. Even if during cooking there is the possibility of adding to the hop contaminated with mycotoxins, the amount is too small to be significant for the final product. In general, about 60% of ZEN is eliminated with used grains.

To avoid massive economic losses, during the technological process of obtaining beer, various processes are applied to eliminate mycotoxins or prevent contamination with them, such as lactic acid bacteria during malting and beer, ozonation, special yeast strains (known to bind mycotoxins), hot barley grains, water treatment or fungicidal failures in the field [124].

Several authors reported that the most common mycotoxins in malt are aflatoxins B1, B2, G1, G2, OTA, PAT, and DON, and in beer are OTA, DON, and sterigmatocystin [90, 127, 128, 129].

3.11 Mycotoxins in coffee, cocoa, and chocolate

According to a meta-analysis by Khaneghah et al. out of 3182 centralized samples from 36 articles, the prevalent and global level of OTA was 53.0% (95% CI: 43.0–62.0) and 3.21 μg/kg (95% CI: 3.08–3.34 μg/kg), respectively. The correlations and the increase of the concentrations of these mycotoxins in the coffee beans were identified, together with the increase of the poverty, but also with the fluctuation of the precipitations from the whole year studied. The lowest concentrations (0.35 μg/kg) of OTA in coffee were reported in Taiwan, and the highest concentrations (79.0 μg/kg) were reported in Turkey [65]. Of the 26 samples of coffee beans and coffee products, 18% were identified with ENN, the average concentration of enniatin was 1901–1901 (g/kg) [130].

According to Batista et al., OTA is the most common mycotoxins in Arabica coffee beans [131]. The same mycotoxins are reported in cocoa beans [132].

In a study of chocolate for sale in Brazil, OTA and AF were identified [133]. Similar results were reported by Kabak et al. for chocolate produced in Turkey [134].

3.12 Mycotoxins in water

Several studies report the presence of mycotoxins in portable water, groundwater, and wastewater. The most common are ZEN, aflatoxin B1, B2, G1, and OTA [135, 136, 137, 138].

3.13 Mycotoxins in nuts

In the study conducted by Alcántara-Durán et al. on mycotoxins in peanuts, pistachios, and almonds, the lowest concentration level was between 0.05 and 5 μg/kg, being lower than the maximum levels established by current legislation [57].

Another mycotoxin identified in pistachios is aflatoxin B1 (AFB1). Rastegar et al. investigated the effectiveness of the frying process by incorporating lemon juice and/or citric acid on the reduction of AFB1 in contaminated pistachios (AFB1 at two levels of 268 and 383 ng/g). Although frying for 1 hour at 120°C, 50 g of pistachios in 30 ml of lemon juice, 6 g of citric acid, and 30 ml of water, led to a good degradation (93.1%) of AFB1, this treatment changed the desired physical properties. In the case of frying for one hour at 120°C, with 15 ml of lemon juice, 2.25 g of citric acid, and 30 ml of water reduced by 49.2% the level of AFB1, from the initial value, without any visible changes of the pistachio in terms of appearance. Thus, a synergistic effect can be observed regarding the degradation of AFB1 between lemon juice, respectively citric acid and heating. In this situation, we can conclude that in the case of pistachios contaminated with AFB1, they can be degraded by frying with lemon juice and citric acid [58].

According to Abrunhosa et al., the most common mycotoxins in pistachios are aflatoxins B1, B2, G1, G2; in peanuts are aflatoxins B1, B2, G1, G2, OTA, and in almonds are aflatoxins B1, B2, G1, G2 [119].

3.14 Mycotoxins in meat

Consumption of dried meat products is increasing, but these products are highly perishable, and when contaminated with fungi, they pose a risk of human exposure to mycotoxins, and therefore, a global public health problem [139]. Dried meat is composed mostly of muscle tissue in which the physicochemical properties of their surface, such as low water activity, neutral to low pH, and nutrient content, cause the microbial population to grow in external layers of these products [140]. Changes in the low activity of water in these products can influence the metabolism of fungi favoring the biosynthesis of mycotoxins [141].

Xerophilous species of Aspergillus, Eurotium, and Penicillium have been shown to grow on the surface of dried meat products in different parts of the world, partly due to the tolerance of these microorganisms at low pH and high salt concentrations [142]. Moreover, the maturation time of the product also influences the growth of microorganisms on the surface of these products.

San Daniele ham, for example, contains NaCl concentrations that vary between 10 and 20% of the dry matter and its maturation lasts between 13 and 18 months [14]. Although these salt levels are impossible for many microorganisms to grow, the long maturation period facilitates the growth of microorganisms well adapted to this environment [143]. In addition, abnormal variations in temperature and humidity commonly encountered in the production of traditional products during the pre-ripening, ripening, and drying stages influence the growth of microorganisms [14, 144].

Regarding toxigenic fungi, four aflatoxins, namely B1, B2, G1, and G2, are considered to be some of the most important mycotoxins in dried meat. Aflatoxin B1 is the most common and has a higher toxigenic potential compared to other aflatoxins [12].

In addition to AF, OTA is an important mycotoxin that has been found in dried meat [30]. OTA was first isolated in 1965 from a culture of Aspergillus ochraceus [18]. OTA can be transferred from food contaminated with mycotoxin [12].

OTA mycotoxin has been identified in Italian salamis [145] and AFB1 and AFB2 in Egyptian salamis [146]. OTA has also been found in blood sausages, liver-type sausages in Germany [147], Parma ham in Denmark [148], and dried Iberian ham in Spain [144, 149].

In a study in Cairo, burgers and sausages had the highest number of mushrooms compared to fresh meat and canned food. This contamination may be related to the addition of AFB1-contaminated spices to burgers [13].

Among the various forms of direct or indirect human exposure to mycotoxins, such as the intake of contaminated meat products, the relationship with human feed should be considered [12].

In a study of 115 chicken samples collected from central Punjab, Pakistan, the presence of AF, OTA, and ZEN was analyzed. The results showed that 35% of chicken samples were found contaminated with AF, and the maximum level of AFB1 was 7.86 μg/kg and total AF was 8.01 μg/kg found in the hepatic part of the chicken. Furthermore, 41% of chicken samples were found to be contaminated with OTA and a maximum level of 4.70 μg/kg was found in the hepatic part of the chicken meat. A total of 52% of chicken samples were found to be contaminated with ZEN and a maximum level of 5.10 μg/kg. The occurrence and incidence of AF, OTA, and ZEN in chicken meat are alarming and can cause health hazards and have called for the need for continuous monitoring of these toxins in chicken meat [16]. In 70 chicken tissue samples (liver, heart, and pipette) collected from the markets of Jiangsu, Zhejiang, and Shanghai (China) the main mycotoxins observed were DON, 15-AcDON, and ZEN [11].

In a study conducted by Rodrigues, they observed that the most common mycotoxin in Portuguese ham of pork, goat, and sheep is OTA [150].

3.15 Mycotoxins in milk and dairy products

In a study by Ezekiel et al. on mycotoxins in breast milk, complementary foods and urine obtained from 65 infants aged 1–18 months in Ogun State, Nigeria, it was observed that complementary foods were contaminated with six types of mycotoxins, including fumonisins identified in 14 of the 42 samples, with a concentration between 8 and 167 μg/kg and aflatoxins identified in 14 of the 42 samples, with a concentration between 1.0 and 16.2 μg/kg. In four out of 22 breast milk samples, aflatoxin M1 was detected, in addition to six other classes of mycotoxins. And for the first time, dihydrocitrinone was detected in six of the 22 samples studied with a concentration between 14.0 and 59.7 ng/L and sterigmatocystin in a sample of the 22 samples studied with a concentration of 1.2 ng/L. Mycotoxins were detected in 64/65 of urine samples, with seven distinct classes of mycotoxins observed demonstrating ubiquitous exposure. Two metabolites of aflatoxin (AFM1 and AFQ1) and FB1 were detected in samples 6/65, 44/65, and 17/65, respectively. The frequency of detection, the average concentrations, and the appearance of mixtures were usually higher in the urine at nonexclusive breastfeeding, compared to breastfed infants.

In conclusion, the study provides new information on mycotoxin exposure in children in a country at high risk of mycotoxin without adequate food safety measures. Although a small set of samples, it highlights the significant transition to higher levels of mycotoxin exposure in infants as complementary foods are introduced, providing an impetus to alleviate this critical early period and encourage breastfeeding [151, 152].

Other authors also reported the presence of mycotoxins in breast milk such as aflatoxin M1, beauvericin, dihydrocitrinone, alternariol monomethyl ether, enniatin A, enniatin B, ochratoxin A, ochratoxin alpha, ochratoxin B, and sterigmatocystin [153, 154].

In milk powder, the most common mycotoxins reported were aflatoxins B1, B2, G1, G2 [84], in milk aflatoxin M1 [154, 155]. Aflatoxin M1 is also found in cheese [156] or yogurt [119].

Mannami et al. conducted a study on 67 samples of liquid milk (46 pasteurized and 21 UHT) randomly collected during 2019 from supermarkets and dairy stores in four Moroccan cities (Casablanca (n = 27), El Jadida (n = 10), Fez (n = 18), and Meknès (n = 12)). The results showed that out of the 67 samples analyzed, AFM1 was identified in nine samples, while 58 samples (86.6%) had AFM1 below the detection limit. According to Moroccan regulations, the maximum limit allowed by AFM1 is 50 ng/l, and it can be observed that a single pasteurized milk sample exceeds the maximum limit allowed by 77 ng/l, by AFM1. According to Codex Alimentarius standards, where the maximum permitted limit is 500 ng/l, all milk samples studied fall within these limits [157].

A study by Marimón Sibaja et al. carried out between 2003 and 2018 in Latin America on aflatoxin (AFM1) from 3547 milk samples and 969 milk products showed that 67% of milk samples were contaminated with AFM1 and had a concentration between 0.001 and 23.10 μg/kg, and 63% of the dairy samples were contaminated with AFM1 and had a concentration between 0.001 and 18.12 μg/kg. According to these studies, referring to AFM1, the highest estimated daily doses were reported for Mexico (20.9 ng/kg body weight/day), Brazil (2.4 ng/kg body weight/day), Colombia (1.2 ng/kg body weight/day), and Costa Rica (1.0 ng/kg body weight/day). During the 15 years of the study, all average values calculated for Latin American countries exceeded the maximum limits allowed by FAO and WHO (0.058 ng/kg body weight per day) [158].

3.16 Mycotoxins in eggs

In a study of 80 egg samples (farm eggs and domestic eggs) collected from the central areas of Punjab, Pakistan, the presence of AF, OTA, and ZEN was analyzed. The results showed that 28% of the samples were found contaminated with AF, and the maximum level of AFB1 was 2.41 μg/kg and the total AF was 2.97 μg/kg. More than 35% of samples were found to be contaminated with OTA and a maximum level of 1.46 μg/kg. A total of 32% of samples were found to be contaminated with ZEN and a maximum level of 2.23 μg/kg. The occurrence and incidence of AF, OTA, and ZEN in chicken meat are alarming and can cause health hazards and have called for the need for continuous monitoring of these toxins in chicken meat [16].

In 152 egg samples collected from the markets of Jiangsu, Zhejiang, and Shanghai (China) the main mycotoxins observed were DON, 15-AcDON, and ZEN [11]. Makun et al. showed that 85% of eggs tested in Nigeria were contaminated with DON at concentrations between 0.6 and 17.9 ng/g [159].

4. Toxic effects on human health caused by ingestion of mycotoxins

Mycotoxins are a public health concern, mainly due to their multiple types and prevalence that can lead to adverse effects due to chronic exposure even when contaminating food at low levels. If ingested, mycotoxins can cause episodes of acute or chronic diseases, such as various types of cancer, food poisoning, liver disease, various hemorrhagic syndromes, immune and neurological disorders in humans [160]. In addition, mycotoxin contamination of food has been linked to cytotoxicity or even genotoxicity [161], which can also induce toxic effects on the liver and kidneys, immune reproduction and fetal toxicity, and teratogenicity and carcinogenicity [162]. Moreover, exposure to a mycotoxin diet has been associated with an increased incidence of esophageal and gastric carcinomas in certain regions of China [163]. Therefore, mycotoxin contamination is a long-term hidden danger to human health, and relentless efforts have been devoted to mycotoxin investigation [10].

In recent years, large-scale poisoning incidents and international trade disputes caused by fungal contamination are extremely common. For example, severe outbreaks of aflatoxinosis have been reported in Kenya, India, and Malaysia, killing hundreds of people. In the United States, mycotoxin corn infection is a chronic economic and health problem. The European Union’s food and feed rapid alert system has placed mycotoxins in second place based on the total number of hazard notifications [10].

Table 1 summarizes the structures of common mycotoxins and the toxic effects they cause on human health. For example, AF toxicity can cause the infant to deform by crossing the placental barrier [183]. In 2018, McMillan et al. confirmed that AF could cause other effects, such as anemia, immunosuppression, and reduced growth rate [165]. In addition, the International Agency for Research on Cancer (IARC) has indicated that exposure to AF may impair renal function in addition to having strong hepatotoxic effects (IARC group 1) (group 1 means carcinogenic to humans), and the same effects have been reported for sterigmatocystin [55]. TA, a toxin produced by Alternaria alternate, has been considered the Alternaria mycotoxin with the highest acute toxicity. Referring to human toxicities, TA has been blamed for the onyalai outbreak, a human hematological disease that occurs in Africa [181].

Mycotoxins	Toxic effect	Reference work
Aflatoxin B1	Development of hepatocellular carcinoma. Cancer and affects the child’s development	[164]
	Anemia, immunosuppression, causing reduction growth rate	[165]
Ochratoxin A	Carcinogenic, teratogenic, immunotoxicity, nephrotoxicity, and neurotoxicity	[10, 166]
Zearalenone	Endometrial cancer	[167]
	Disorders of the hormonal balance of the body; prostate, ovarian, cervical, or breast cancers	[168]
Deoxynivalenol	Emesis, anorexia, growth retardation, immunotoxicity, reproduction, and development resulting from maternal toxicity. Altered neuroendocrine signaling, proinflammatory gene induction, disruption of the growth hormone axis, and altered gut integrity	[169]
	Nausea, vomiting, diarrhea, abdominal pain, headache, dizziness, fever, and effects on reproduction	[170]
Fumonisin B2	Teratogenic, hepatotoxic, and nephrotoxic	[161]
T-2 toxin	A latent inhibitor of mitochondrial function and protein synthesis	[171]
	Causing low growth and side effects on the thymus, spleen, heart, and liver	[172]
Beauvericin	Induction of apoptosis, increases the concentration of cytoplasmic calcium	[173]
Patulin	Impairment of some of the physiological parameters that characterize the intestinal barrier function	[174]
Citrinin	Impaired renal function in addition to strong hepatotoxic effects	[10]
α-Cyclopiazonic acid	Weight loss, nausea, diarrhea, dizziness, muscle necrosis, seizures	[175]
Enniatin B	Cytotoxic effect for different cell lines and reduces the motility of wild boar sperm	[176]
Alternariol	DNA damage	[177]
	Genotoxic in bacteria and mammalian cells in vitro	[10]
Sterigmatocystin	Genotoxic cytotoxic effects	[178]
	Induction of DNA damage in HepG2 cells	[179]
Fusaric acid	Modification of neurotransmitter levels by inhibition of dopamine hydroxylase and modulation of tyrosine hydroxylase	[180]
Tenuazonic acid	Inhibition of protein biosynthesis; causing precancerous changes in the esophageal mucosa of mice	[181]
Mycophenolic acid	Nausea, vomiting, stomach cramps, and diarrhea; infections hematological complications (anemia, leukopenia, neutropenia); cytostatic effects on lymphocytes	[182]

Table 1.

Toxic effects caused by the main mycotoxins.

In recent years, large-scale poisoning incidents and international trade disputes caused by fungal contamination are extremely common. For example, severe outbreaks of aflatoxinosis have been reported in Kenya, India, and Malaysia, killing hundreds of people. In the United States, corn mycotoxin infection is a chronic economic and health problem [10]. The European Union’s food and feed rapid alert system has placed mycotoxins in second place in terms of the total number of hazard notifications.

CIT affects kidney function but has been shown to be less toxic than OTA. The latter has carcinogenic, neurotoxic, immunotoxic, and teratogenic effects, exerting nephrotoxicity. According to IARC group 2B (group 2B means possible human carcinoma) both OTA and fumonisins have carcinogenic effects on kidney cells) [10]. It is called vomitoxin because it can lead to some typical acute effects, including nausea, vomiting, abdominal pain, diarrhea, headache, dizziness, or fever, which has also been linked to outbreaks of gastroenteritis in animals and humans. In addition, DON acts as a potent inhibitor of protein synthesis and stimulates the pro-inflammatory response, resulting in the impairment of multiple physiological functions. NIV has been demonstrated with immunotoxicity, hematotoxicity, myelotoxicity, and developmental and reproductive toxicity [169]. T-2 is a latent inhibitor of mitochondrial function and protein synthesis. Moreover, T-2 has toxic effects on the skin and mucous membranes [171].

Long-term ingestion of PAT has shown immunotoxicity, mutagenicity, and neurotoxicity in animals [112]. Trichothecenes are a large family of structurally related mycotoxins among which DON is the most common worldwide [184]. DON has high immunotoxic and immunosuppressive effects against a variety of animal and human cells [88].

DAS exerts acute and chronic effects on humans and animals, such as hematotoxicity, growth retardation, lung disorders, immunotoxicity, and cardiovascular effects [26]. In addition, Vidal et al. linked DAS toxicity to distal tubular epithelial necrosis in the kidney [184]. Fumonisins cause a lot of negative effects on humans and animals, such as teratogenic, hepatotoxic and nephrotoxic, esophageal cancer, liver cancer, and neural tube defects [161]. Belhassen et al. confirmed that ZEN stimulates the growth of human breast cancer cells [185], but IARC classified ZEN in group 3 (IARC) (group 3 does not mean carcinogenic effects on humans). In addition, ZEN has strong estrogenic activity and may be an essential etiological agent of infant intoxication, leading to premature enlargement of puberty and breast enlargement. Moreover, IARC reported that FUS-X mainly affects organs that have actively dividing cells, including hematopoietic tissue, spleen, and thymus, as well as exerts intestinal inflammation, inhibits protein synthesis, and induces apoptosis. However, the toxicity of mycotoxins is not stationary, which changes during metabolism in humans and animals [10]. In addition, the assessment of adverse health effects is complicated by multiple exposures to various mycotoxins that can lead to synergistic or antergic toxic effects [186]. Furthermore, the susceptibility of animals and humans varies according to species, age, nutrition, duration of exposure, and other factors [187]. Therefore, the synergistic or antergic toxic effects of different mycotoxins should attract more attention, which is also a new topic in mycotoxin toxicity research.

In addition, a wide range of masked mycotoxins that have been produced by plant phase II metabolism may co-appear as contaminants in addition to parent compounds in food samples. The group of masked mycotoxins comprises both conjugated extractable and related varieties. Bound mycotoxins are attached to carbohydrates or proteins by covalence or non-covalence, which cannot be detected directly and must be released from the matrix by chemical or enzymatic treatment before detection [188]. Regarding the toxicity of masked mycotoxins, on the one hand, these mycotoxins can degrade in free states in the digestive tract of humans and animals, releasing their prototypes of toxins, thus increasing exposure to toxins and posing a greater threat to human health. On the other hand, changes in mycotoxin molecules that reduce or eliminate toxicity can lead to an apparent overestimation of mycotoxin contamination. Thus, it is necessary to understand the fate of masked mycotoxins during food processing and digestion. Khaneghah et al. conducted a comprehensive review of changes in DON masked forms and their occurrence in combination with culmorin in grain-based products [189]. They also comprehensively exposed the characteristics, incidence, control, and fate of DON and its masked forms [190]. However, there are only limited data reported on the occurrence of masked mycotoxins in food, as well as information on the transformation, stability, and release of masked mycotoxins in the food chain. Moreover, masked mycotoxins easily escaped conventional detection due to the biotransformation of their structures, leading to underreporting [191]. In view of the above, it is essential to pay more attention to the subsequent investigation of masked mycotoxins, in particular their occurrence, exposure, toxicity, and nontarget screening.

5. Conclusions

The purpose of this chapter was to analyze the significant types of mycotoxins in food that are consumed directly or indirectly by humans. Studies show that contamination of various mycotoxins is still high in developing countries and remains the main concern in these regions. In recent years, most reports of contamination have been reported for maize, wheat, and rice, respectively. AFB1 are considered the most dangerous mycotoxins and have a high prevalence in cereals that in most studies exceeded the EC permitted limit. DON, ZEN, and FUM are the other significant mycotoxins in cereals, such as barley, sorghum, and oats.

The high stability of mycotoxins during the production, distribution, storage, and processing of cereals was aimed at the contamination of mycotoxins in cereals. Therefore, the development of practical control and management strategies is essential to ensure consumer safety.