**3.3** *Fusarium* **toxins**

*Mycotoxins and Food Safety*

contaminated with aflatoxin [40].

**3.2 Ochratoxin A**

aflatoxin production at 24° C, and no production at temperatures below 13°C or above 42°C and relative humidity below 70% [30]. Heat processing, such as ultrahigh-temperature (UHT) treatment, pasteurization, roasting, and baking, and also cold storage do not affect aflatoxin in foods since they are fairly stable and resistant [31, 32]. Approximately more than 14 various chemical forms of AF are present in nature; however, the most dangerous ones are aflatoxins B1, B2, G1, and G2 [33]. The nomenclature of aflatoxins with these letters is based on the color they exhibit under ultraviolet radiation (B, blue, and G, green) [34]. Various food products especially grown in hot and humid regions of the world are susceptible to fungal invasion and aflatoxin production, including groundnuts, maize, various spices, tree nuts, cottonseed, pistachios, copra, wheat, rice, etc. [25]. AFB1 is converted into metabolized AFM1 and excreted in milk in both human and lactating animals [35]. The European Commission, Codex Alimentarius Commission, Germany, Turkey, Switzerland, France, Sweden, Belgium, Argentina, Iran, and Honduras have regulated an acceptable limit for AFM1 at 50 ng/L for infants, for raw, pasteurized, and UHT milk. On the other hand, the United States, Brazil, China, Bulgaria, Czech Republic, Kuwait, and Serbia have accepted 500 ng/L level for AFM1 [31]. Aflatoxin contamination causes huge economic and critical health problem due to their high toxicity. For example, aflatoxin contamination is estimated to cause damages to the corn industry in the United States ranging from US \$ 52.1 million to US \$ 1.68 billion [36]. They are carcinogenic, hepatotoxic, and teratogenic, decrease immune systems, poison the body through respiratory, and can directly affect the structure of DNA [37]. Of all the human health effects associated with aflatoxin exposure, the weight of evidence is strongest for aflatoxin-related liver cancer and secondarily of the synergism between aflatoxin exposure and chronic HBV infection in liver cancer risk [38]. In 1974, there was an outbreak of hepatitis due to aflatoxin in India, resulting in an estimated 106 deaths [22]. In 2004 the largest outbreak was ever recorded, where 317 people became ill and 125 people died because of consumption moldy maize which early harvested and stored improper harvested condition [39]. In 2013, countries in Europe, including Romania, Serbia, and Croatia, reported that nationwide milk was

Ochratoxin A (OTA) is a natural mycotoxin produced mainly by fungal type of *Aspergillus* and *Penicillium* under optimum environmental conditions and storage especially tropical and subtropical regions such as Eastern and South Europe, Canada, and South America [41, 42]. There are three types of ochratoxins, namely A, B, and C. Especially, OTA is known as the most common and important one for public and animal health. Although people are exposed to OTA by inhalation or dermal contact, various foods are the main source of exposure to OTA including maize, sorghum, wheat, rice, barley, rye, bread, oats, flour, pasta, grapes, infant cereals, apples, peaches, strawberries, pears, oranges, figs, mangoes, wine, tomatoes, coffee beans, watermelons, nuts, rapeseed, sesame seeds, spice, soybeans, cocoa, peanuts, chickpeas, milk and milk-based baby formulae, eggs, cheese, yam, potatoes, garlic, onions, fish, pork, poultry, jerky, and dried beans [43]. Recently, the presence of OTA has been detected in bottled water [44], plant food supplement, and food coloring agent [45]. According to the European Commission report, the estimated adult exposure to OTA is as follows: 44% cereals, 10% wine, 9% coffee, 7% beer, 5% cacao, 4% dried fruits, 3% meat, 3% spices, and 15% others [46]. For the first time in 1970, the presence of OTA was detected in human blood in Balkans [47]. In the review of Malir et al., published data on OTA in human blood samples from healthy persons were compiled, and concentrations higher than 1.0 g/L were observed in several countries [48].

**48**

*Fusarium* toxins are secondary metabolites synthesized by toxigenic molds including *Fusarium oxysporum*, *F. culmorum*, *F. roseum*, and *F. graminearum* [50]. Fumonisins (FBs), zearalenone (ZEA), trichothecenes, deoxynivalenol (DON), and nivalenol (NIV) are the most common *Fusarium* mycotoxin groups [51]. Recently fusaproliferin (FUS), beauvericin (BEA), enniatins (ENNs), and moniliformin (MON) are discovered but less studied [52]. *Fusarium* disease outbreak on cereal products such as wheat, barley, and maize causes worldwide economic losses due to yield loss and reduced grain quality, for example, losses in the United States of \$ 1–20 million in a normal year and \$31–46 million in a year [53]. *Fusarium* mycotoxin has both acute and chronic toxic effects and been shown to cause a wide variety of toxic effects in animals [54]. Spontaneous outbreaks of *Fusarium* mycotoxicosis have been reported in Europe, Asia, Africa, New Zealand, and South America. Moreover, chronic intake of these mycotoxins is reported on a regular and more widespread basis due to their global occurrence [55]. *Fusarium* mycotoxin limits specified in unprocessed cereals, milling products, and cereal foodstuffs are 200–1750 μg/kg for DON, 20–400 μg/kg for ZEN, and 200–4000 μg/kg for the sum of B1 + B2 fumonisins (FB1 + FB2 combined) according to the European Commission (19 December 2006).

#### *3.3.1 Fumonisin*

Fumonisins are generated by various fungal species such as *Fusarium verticillioides* and *F. proliferatum* also by *A. niger* and were discovered in 1988 in South Africa [56, 57]. Nowadays 28 types of fumonisin have been identified that are divided into four groups, fumonisins A (A1, A2, and A3), fumonisins B (B1, B2, and B3), fumonisins C (C4, C3, and C1), and fumonisins P (P1, P2, and P3), but the most important group of fumonisins is the B group, which contains fumonisins B1 (FB1), B2 (FB2), B3 (FB3) [58].

The International Agency for Research on Cancer (IARC) identified FB1 as possibly carcinogenic to humans (group 2B). Recent studies reported that FB1 causes an increased prevalence of esophageal and liver cancer in humans [59]. Furthermore, this mycotoxin has been found to have toxic effects against several organs (nervous and cardiovascular systems, liver, lung, kidney) in animals [60]. Fumonisins are largely found in corn and corn-based foods and also FB1 in rice, beer, sorghum, cowpea seeds, triticale, beans, asparagus, and soybeans [61].

#### *3.3.2 Zearalenone (ZEA)*

Zearalenone (ZEA), known as an estrogenic mycotoxin, is a secondary metabolite produced by *Fusarium* species such as *F. graminearum*, *F. culmorum*, *F. cerealis*, *F. equiseti*, *F. crookwellense*, and *F. semitectum* (mainly *F. culmorum* and *F. graminearum*) [62]. The main contamination source of ZEA is cereal-based foods such as maize, sorghum, wheat, rice, barley, oats, and also nuts, soybean, and sesame [63].

Several in vivo studies found that ZEA disrupts hormonal balance due to its similarity to naturally occurring estrogens [64]. The mycotoxin has high affinity for estrogen receptors, causing reproduction and fertility disorders in mammals [65]. In addition, it is known that progressive exposure to endocrine-modulatory compound has been linked with carcinogenesis in human [64]. According to the European Food Safety Authority (EFSA) report in 2014, the bioavailability of toxin is up to 80% in human and animals such as rats, rabbits, and pigs [66]. Moreover, recent works report ZEA is metabolized in the liver and has shown hepatotoxic, immunotoxic, carcinogenic, and nephrotoxic effect in animal tests [67–69]. As this mycotoxin possesses such consumer health risks, the European Union (EU) has prescribed the limits of ZEA (20–350 μg/kg) for various processed and unprocessed cereals [66].
