The term mycotoxin designates a chemically diverse group of secondary fungal metabolites ^[1][2][3][1,2,3], mainly produced by species of the Aspergillus, Penicillium or Fusarium genus ^[4][5][4,5]. Depending on classification, 300–400 mycotoxins are known today [6]. Contamination may occur in the field as well as during (improper) storage and is largely dependent on environmental factors ^[7][8][7,8]. When ingested by humans or animals above a certain concentration, mycotoxins will cause a toxic response referred to as mycotoxicosis ^[1][4][5][1,4,5]. The symptoms elicited by mycotoxin consumption range from reduced animal productivity (reduced body weight gain, reduced fertility) and immune suppression [9], resulting in increased susceptibility to diseases and parasites to overt disease and death. Clinical symptoms of mycotoxin intoxication include diarrhea, liver and kidney damage, pulmonary edema, vomiting, hemorrhaging and tumours ^[1][7][1,7]. Under field conditions, mycotoxins usually occur in concentrations leading to reduced animal performance and/or immune suppression without causing any obvious clinical symptoms ^[5][8][5,8]. It is important to emphasise that it is very common for an array of mycotoxins to occur together at low concentrations. This is on the one hand due to the ability of various fungi to simultaneously produce a variety of mycotoxins ^[10][11][10,11] and on the other hand due to the fact that any given commodity is likely to be infected with different types of fungi. Moreover, compound feed is made up of a number of different commodities contributing to the final mycotoxin profile.

In the feed manufacturing process, only a limited number of mycotoxins are subject to regular testing and legal regulations/guidance ^[12][13][12,13], namely aflatoxins (AF), deoxynivalenol (DON), zearalenone (ZEN), fumonisins (FB) and ochratoxin A (OTA).

2. Aflatoxins

Aflatoxins (B₁, B₂, G₁ and G₂) are considered to be the group of mycotoxins of greatest concern from a global perspective [4]. They are primarily produced by Aspergillus flavus, A. parasiticus and, in rare cases, by A. nomius [14]. AFB₁, the most abundant and most toxic aflatoxin [15], is often referred to as the most potent naturally occurring carcinogen [4]. It is classified as a Group 1 human carcinogen by the International Agency for Research on Cancer (IARC) [16]. Lactating animals fed AFB₁ contaminated diets will produce milk contaminated with its monohydroxylated derivative AFM₁ [15], classified as 2B, possibly carcinogenic to humans [16]. Aflatoxin production occurs primarily in regions with tropical or subtropical climates. Hence, from a European perspective, imported feed such as peanut cake, palm kernel, copra and corn gluten meal (depending of origin) is considered to be the most common source of exposure [15]. However, the EFSA report also cites findings from Italy reporting the detection of AFB₁ in maize originating from the Po valley after a growth period characterized by high temperatures, drought and strong insect damage. As a result, regional milk samples collected after this particular harvest were found to be contaminated with AFM₁ concentration exceeding EU limitations. The incident occurred in 2003 and is discussed in more detail in the section on mycotoxin occurrence in Europe. The main target organ of aflatoxin toxicity is the liver [15]. Long term exposure of animals to subacutely toxic levels of AFs is associated with liver lesions and/or tumours [17], inferior egg shell and carcass quality, increased disease susceptibility [5], reduced feed efficiency [18], and teratogenicity [1].

3. Deoxynivalenol

Deoxynivalenol (DON) belongs to the trichothecene group and, albeit being one of its least acutely toxic members, is of particular interest owing to its high prevalence [19]. More precisely DON is classified as type-B trichothecene [20]. It is produced by Fusarium culmorum and F. graminearum ^[10][19][10,19]. DON contamination is observed worldwide, with cereal crops such as wheat, maize or barley being most frequently affected [20]. Furthermore, silage contamination is regularly observed [21]. Cold and wet weather conditions favour DON production [19] and it was found that the timing of the rainfall is more influential than the amount of precipitation ^[20][22][20,22]. In animal husbandry, DON, also known as vomitoxin, is primarily known for causing feed refusal and emesis in pigs [7]. This mycotoxin also alters the immune response ^[9][23][9,23] and the intestinal functions [24]. DON may be produced together with two acetylated derivatives, 3-AcDON and 15-AcDON, that have differential toxicity on pig intestine [25]. Poultry are not as sensitive to DON [26] and feed refusal is only observed at very high concentrations (16–20 mg/kg feed) [20]. Ruminants are the least sensitive animal species to DON, a fact that is attributed to the capacity of rumen microflora to detoxify this mycotoxin [19].

4. T-2 Toxin and HT-2 Toxin

T-2 and HT-2 toxin are two of the most toxic members of the trichothecene group. They belong to the type A-trichothecenes and are produced by F. sporotrichioides, F. poae and other Fusarium species ^[27][28][27,28]. Oats and oat products were found to be particularly prone to contamination with high levels of T-2 and HT-2 [29] followed by barley [27]. Toxicity data on T-2 and HT-2 are notoriously scarce compared to the other mycotoxins addressed in this resviearchw. They were found to impair protein synthesis and exert immunotoxic, haematotoxic and myelotoxic effects ^[29][30][29,30]. Dietary exposure to T-2 and HT-2 was reported to weaken acquired immune response in pigs [31] and cause oral lesions in poultry ^[32][33][32,33]. Feed intake depression and reduced weight gain have been observed in both species ^[32][33][34][32,33,34]. Higher T-2/HT-2 concentrations were furthermore found to negatively influence egg production and egg shell thickness in laying hens ^[35][36][35,36]. Pigs are most sensitive to T-2/HT-2, followed by poultry. Ruminants are again protected by their microflora and found to be least sensitive to these toxins [29]. A comprehensive review on the occurrence of T-2/HT-2 in Europe was provided by van der Fels-Klerx [27]. As a matter of fact, reports on T-2 and HT-2 occurrence are largely restricted to Europe, most often coming from the northern parts of the continent like Scandinavia or the UK ^[27][28][27,28]. When guidance values were set for the other major mycotoxins in feed in 2006 by the European Commission data on T-2/HT-2 were deemed too scarce for setting scientifically sound guidance values and further monitoring was recommended [13]. In a recent opinion piece, the EFSA panel on contaminants in the food chain (CONTAM) concluded that based on available data the animal health risk from dietary exposure to T-2/HT-2 was low [29].

5. Zearalenone

Like DON, zearalenone (ZEN) is produced by fungi of the Fusarium genus. F. culmorum, F. graminearum and F. heterosporum are among the species found to produce ZEN [10]. Again the risk of contamination is highest in cereal crops [37] but silages, forage, and straw are also likely to contain ZEN ^[7][21][7,21]. Acute toxicity of ZEN is low and adverse effects observed are caused by its ability to interact with the estrogen receptor [37]. Consequently ZEN is mainly associated with fertility problems and hyper estrogenic symptoms such as swelling of the vulva and uterus enlargement ^[1][5][38][1,5,38]. Female swine are most sensitive to ZEN exposure [37] whereas poultry are found to be very tolerant [38]. It is very unlikely that naturally contaminated feedstuff contains ZEN at concentrations sufficiently high to cause adverse effects in poultry. Data on dairy cows is limited but also suggests low responsiveness to ZEN [37].

6. Fumonisins

Fumonisins are also counted among the Fusarium mycotoxins. In feed crops they are most commonly produced by F. proliferatum and F. verticillioides. Of the numerous fumonisin analogues known, the B series (FB₁, FB₂, and FB₃) is the most important regarding occurrence and toxicity. FB₁ is of greatest concern, as it is the most prevalent and the most toxic of the fumonisins [39]. It has been classified as 2B, possibly carcinogenic to humans [40]. Fumonisin contamination is commonly associated with maize and maize products ^[39][41][39,41]. In a wider context the classification of fumonisins as Fusarium mycotoxins is no longer valid as recently black aspergilli, most notably A. niger, were also found capable of producing fumonisins [42]. They were reported to cause severe contamination of dried grapes with FB_1–4 and other fumonisin isomers [43]. Fumonisin contaminated feed will cause severe diseases like pulmonary edema in swine and leukoencephalomalacia in horses [44]. Furthermore, fumonisins were found to be immunosuppressive ^[5][45][46][5,45,46], hepatotoxic, and nephrotoxic [1]. Fumonisins, DON and ZEN are considered to be the most important exponents of the Fusarium mycotoxins with regard to animal health implications ^[41][47][41,47] and associated economic loss [48]. Although fumonisin contamination is not very common in crops other than maize, Fusarium mycotoxins in general are often found to occur together in contaminated cereals ^[20][41][47][20,41,47]. In most cases, the resulting toxic effects will be additive combinations of the mycotoxins’ individual toxicities but synergistic interactions have been observed ^[47][49][47,49].

7. Ochratoxin A

Ochratoxin A (OTA) contamination is predominantly associated with insufficient drying or improper storage. It is found all over the world. In temperate regions, OTA contamination is mostly due to Penicillium verrucosum infection while Aspergillus species such as A. carbonarius account for OTA production in warmer regions ^[50][51][50,51]. As for feed ingredients, OTA is most frequently found in cereals but is also known to contaminate soy beans and peanuts. Since fungal growth often occurs at localised hot spots (i.e., an area of elevated water activity) in the stored grain, OTA distribution in contaminated feed lots tends to be very heterogeneous. This fact poses a particular challenge when testing for OTA contamination [50]. Ochratoxin A has been classified as possibly carcinogenic to humans (Group 2B) [52]. The primary target organ for OTA toxicity is the kidney [51]. OTA contamination has been linked to outbreaks of nephropathy in pigs and poultry. It is furthermore associated with immunosuppression, reduced growth rate and increased mortality ^[50][51][50,51]. Owing to their rumen microflora’s ability to degrade OTA to the less toxic ochratoxin α, ruminants are less sensitive to OTA. However, negative effects on milk production have been described [51]. With regards to OTA residues in animal derived food, specialities made from porcine blood are of most concern. Accumulation in kidney and liver was also observed although at a lesser extent. However, it is estimated that animal derived foodstuff only accounts for 3%–10% (depending on eating habits) of human dietary exposure to OTA in Europe [50].