Deoxynivalenol and its masked forms: Characteristics, incidence, control and fate during wheat and wheat based products processing - A review

Trends in Food Science & Technology 71 (2018) 13–24

Contents lists available at ScienceDirect

Trends in Food Science & Technology journal homepage: www.elsevier.com/locate/tifs

Deoxynivalenol and its masked forms: Characteristics, incidence, control and fate during wheat and wheat based products processing - A review

MARK

Amin Mousavi Khaneghah, Ligia M. Martins, Aline M. von Hertwig, Rachel Bertoldo, Anderson S. Sant’Ana∗ Department of Food Science, Faculty of Food Engineering, University of Campinas, Campinas, SP, Brazil

A R T I C L E I N F O

A B S T R A C T

Keywords: Fusarium Grains Mycotoxins Fungi Storage Dough Pasta Bread

Background: Deoxynivalenol (DON) is a toxic secondary metabolite primarily produced by Fusarium graminearum and Fusarium culmorum that is common in grains, such as wheat and wheat-based products. Scope and approach: This review points out on the main DON-producing fungi, the factors affecting DON production, its toxicological aspects and preventive measures to avoid contamination of foods by DON. Further, the article discusses the fate of DON throughout the processing of wheat, bread, and pasta and finally critically assesses data on the impact of specific steps of processing on DON contents in wheat-based products. Key findings and conclusions: The proposed controls at pre- and post-harvest stages seem to comprise the most efficient strategies to manage the incidence of DON in wheat and wheat-based products. Prevention of plant infection by Fusarium species, managing crops and ensuring the rapid drying of wheat after harvest is the effective approaches for the elimination of DON contamination. There has been contradictory data in the literature on the fate of DON during wheat and wheat-based products processing Due to differences in processing, such as temperature, additives, processing time and loaf size in addition to the occurrence of modified (masked) forms of DON. Therefore, further research must be carried out aiming to reveal the formation and occurrence of modified forms of DON. These compounds can be formed throughout wheat processing, from pre-harvest to processing of wheat-based products, and for proper quantification, analytical methods able to quantify modified forms of DON are required.

1. Introduction Wheat (Triticum aestivum) is amongst the most common farmed plants worldwide, and wheat-based products can be categorized as the primary sources of calories and protein originated from vegetable sources for the human diet (Jones, 2005). Wheat grains are typically processed into flours, which are employed in the manufacturing of bread, pasta, and cookies, for culinary purposes or in other industrial sectors. Moreover, wheat is highly relevant from both economic and nutritional points of view, but it is susceptible to fungal contamination. Fungal disease of wheat may culminate in the reduction of grain quality and the production of toxic metabolites, the so-called mycotoxins (i.e., secondary metabolites with toxic properties that are formed by fungi) (Filtenborg, Frisvad, & Thrane, 1996). In another word, humans and animals can be threatened by natural toxicants that occur in food and feed. Mycotoxins are “secondary metabolites produced by a few fungal species belonging mainly to the Aspergillus, Penicillium and Fusarium genera”. They may be formed by these mycotoxigenic molds when

∗

growing in contaminated foods at different stages of, processing as well as during storage. Deoxynivalenol, trichothecenes, zearalenone, aflatoxins, patulin, fumonisin, ochratoxin, and ergotamine can be considered as the main types of mycotoxins which pose challenges to the safety of feed production and food processing due to consequence negatively effects on human health and the economy (Amirahmadi, Shoeibi, Rastegar, Elmi, & Mousavi Khaneghah, 2017; Campagnollo et al., 2016). Among them, the most common mycotoxin associated with wheat is deoxynivalenol (DON), which is also called vomitoxin (a type B trichothecene) (Sobrova et al., 2010). DON is produced mainly by Fusarium species such as F. graminearum (Gibberella zeae teleomorph) and F. culmorum. Both F. graminearum and F. culmorum are listed as pathogens for wheat that cause a disease named Fusarium head blight (FHB) which also identified as scab, leads to a reduced yield, lower grade and end-use quality of the wheat grains, as well as limiting crop rotation. The occurrence of FHB may result in accumulation of DON and other trichothecenes types in the plant, as affected by the chemotype of the fungus (Cirlini et al., 2014; Malbrán, Mourelos, Girotti,

Corresponding author. Rua Monteiro Lobato, 80, Cidade Universitária Zeferino Vaz, CEP: 13083-862, Campinas, SP, Brazil. E-mail address: [email protected] (A.S. Sant’Ana).

http://dx.doi.org/10.1016/j.tifs.2017.10.012 Received 15 April 2017; Received in revised form 12 October 2017; Accepted 23 October 2017 0924-2244/ © 2017 Elsevier Ltd. All rights reserved.

Trends in Food Science & Technology 71 (2018) 13–24

A.M. Khaneghah et al.

acute intoxication was established as 50 μg/kg body weight (JECFA, 2011). In order to represent the susceptibility of animals to DON, Pestka (2007) proposed a rank: “pigs > mice > rats > poultry ≈ ruminants.” The ingestion of DON can result in both acute and chronic toxic effects. The acute symptoms include abdominal discomfort, malaise, diarrhea, increased salivation, vomiting, and anorexia. The most frequently observed effects of chronic exposure to DON can be classified as altered nutritional efficiency, weight loss, and anorexia (Pestka, 2007). Nonetheless, sensitivity to DON can vary according to the metabolism, absorption, circulation, and elimination of DON by the organism (Sobrova et al., 2010). The toxicity of trichothecenes is related to the inhibition of protein synthesis in eukaryotes. When trichothecenes bind to the 60S of the ribosomes, as result of interaction with peptidyl transferase enzyme, inhibition of translation occurs (Sudakin, 2003). Moreover, activation of kinase proteins by trichothecenes can lead to the induction of apoptosis via the response to ribotoxic stress (Iordanov et al., 1997). The kinase proteins PKR (kinase protein activated by RNA) and HCK (hematopoietic cell kinase) are involved in the activation of (mitogens) MAPKs, consequently of transcription factor expression induced, gene expression and apoptosis increased. Leucocytes are the primary targets of trichothecenes and depending on the dose, frequency and exposure time; trichothecenes can cause immunosuppression or immune stimulation (Pestka, 2007). DON and its acetyl derivatives [3-acetyl-DON (3-Ac-DON) and 15acetyl-DON (15-Ac-DON)] were defined as Acute Reference Dose (ARfD) with eight μg/kg b × w, by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 2010 (European Food Safety Authority, 2013). Furthermore, the established limits by EC for DON in different categories of food products can be summarized as foodstuffs derived from barley, maize and wheat, (1000 μg/kg), bread, cereal snacks pastries, breakfast cereals and biscuits (500 μg/kg), pasta (dry) (750 μg/kg), processed cereal-based foods for toddlers and young children (200 μg/kg) (European Food Safety Authority, 2013).

Balatti, & Lori, 2014). Furthermore, due to plant responses, matrix effects and reactions occurred during food processing, modified and other configurations of DON can be formed in wheat and wheat-based products (Berthiller et al., 2013; Rychlik et al., 2014). The presence of these modified forms of DON (i.e., masked mycotoxin) has been raising significant concerns regarding the safety of contaminated products. Also, the masked mycotoxins may represent analytical challenges, as the native mycotoxin may not be detected while the modified mycotoxin still retains the toxicological effects (Galaverna, Dall’Asta, Mangia, Dossena, & Marchelli, 2009). Given the association of FHB and presence of DON, the consumption of contaminated wheat and wheat-based products, such as bread and pasta, appears to comprise a significant source of human exposure to DON. Also, DON is the primary compound responsible for economic losses due to the reduction of performance in animal husbandry (Morgavi & Riley, 2007). In implementing effective scientific-based control strategies to reduce consumers' and animal's exposure to DON, it is of foremost importance to know not only the real incidence of this mycotoxin in raw materials and final products but mainly the fate of this mycotoxin during wheat, bread, and pasta processing steps. Therefore, in this review, the characteristics of DON, toxicological-related aspects, primary producing fungi, masked forms and factors affecting DON production are examined. Besides, preventive measures to avoid DON production and the impact of wheat, bread and pasta processing on DON levels were also discussed. 2. Characteristics and toxicological aspects 2.1. DON DON [(3α,7α)-3,7,15-trihydroxy-12,13-epoxytrichothec-9-en-8one] (C15H20O6) has a molar mass of 296.3 g/mol and exists as colorless thin crystals that are solvable in polar organic solvents, such as aqueous solutions of chloroform, ethanol, acetonitrile, methanol and ethyl acetate. Some previous investigations have reported that DON is a stable compound at temperatures ranging from 170 to 350 °C (Generotti et al., 2015; Gärtner, Munich, Kleijer, & Mascher, 2008; Lancova et al., 2008; National Toxicology Program, 2009; Numanoglu, Uygun, Koksel, & Solfrizzo, 2010). However, a report from the World Health Organization states that “DON is stable at 120 °C, moderately stable at 180 °C and partially stable at 210°C” (WHO, 2001). It can be categorized in the group of trichothecenes, which are sesquiterpenoids containing a central nucleus of hexane cyclic rings and tetrahydropyran (Fig. 1, Table 1). Fusarium species could synthesize different sorts of mycotoxins such as mycoestrogens and trichothecenes. The four types of trichothecenes, which are types A, B, C, and D, with T-2 toxin and HT-2 (HT-2) synthesized by F. poae, F. langsethiae and F. sporotrichioides toxin being classified as a type A trichothecene. Type C and D trichothecenes are not related to wheat diseases (Foroud & Eudes, 2009). The most common forms of trichothecenes are deoxynivalenol (DON, type B along with nivalenol (NIV) and NIV by-products) by F. graminearum and F. culmorum (Liang et al., 2014; Pasquali & Migheli, 2014). DON was classified in group 3 by the International Agency for Research on Cancer (IARC), which means that this mycotoxin is not carcinogenic to humans (IARC, 1993; Ostry, Malir, Toman, & Grosse, 2017). The provisional maximum tolerable daily ingestion of DON is one μg/kg body weight (including DON acetylated derivatives, i.e., 3Ac-DON and 15-Ac-DON). In humans, the level improbable to cause

2.2. DON – modified forms Even though properties and toxicological effects of the native (free) form of DON have been well known, data on modified or matrix-associated forms of mycotoxins (masked mycotoxins) comprise a topic of increased interest (Berthiller et al., 2013; Rychlik et al., 2014). Because of their growing importance, a categorization consisting of four hierarchic levels has been suggested (Rychlik et al., 2014). The modified mycotoxins can be first divided into free, matrix-associated and modified forms. Matrix-associated mycotoxins can be found as complexes (dissolved or trapped) or covalently bound, while modification can be biologically or chemically driven. The third level in biological modification includes functionalization and conjugation, with the latter being powered by plants, animals, and fungi (fourth level). The third level of chemically modified mycotoxins includes thermally and nonthermally modified forms (Rychlik et al., 2014). The great concern over the natural occurrence of matrix-associated or modified mycotoxins in raw materials and food products are supported by the fact that their chemical behavior can pose challenges for analytical quantification while the structures can still retain toxic effects (Galaverna et al., 2009). These forms of mycotoxins could be potentially reactivated at specific conditions such as in gastrointestinal tract (Berthiller et al., 2013). For example, the ingestion of foods containing DON-3-Glc is of concern due to resistance properties of DON against the acidic conditions in the stomach and the action of digestive enzymes. The conversion of DON-3-Glc to DON due to the action of bacteria belonging to the Lactobacillus, Enterococcus, Enterobacter and Bifidobacterium genera (as normal microflora of gut) was demonstrated in vitro (Berthiller et al., 2011). Thus, the toxic effects associated with DON consumption can be worse than those estimated based on the

Fig. 1. Trichothecenes structure. (Schothorst & Jekel, 2001; with permission).

14

Trends in Food Science & Technology 71 (2018) 13–24

A.M. Khaneghah et al.

Table 1 Structure of trichothecenes (Schothorst & Jekel, 2001; with permission). Type

Trichothecene

R1

R2

R3

R4

R5

Elemental Formula

Molecular mass (amu)

A A A A B B B B

Diacetoxyscirpenol Neosolaniol T-2 Toxin HT-2 Toxin Deoxynivalenol 3-Acetyldeoxynivalenol Fusarenon X Nivalenol

OH OH OH OH OH OCOCH3 OH OH

OCOCH3 OCOCH3 OCOCH3 OH H H OCOCH3 OH

OCOCH3 OCOCH3 OCOCH3 OCOCH3 OH OH OH OH

H H H H OH OH OH OH

H OH OCOCH2CH(CH3)2 OCOCH2CH(CH3)2 =O =O =O =O

C19H26O7 C19H26O8 C24H34O9 C22H32O8 C15H20O6 C17H22O7 C17H22O8 C15H20O7

366 382 466 424 294 338 354 312

2.2.1. Detection methods Masked mycotoxins typically elude detection using standard chemical analytical techniques (Berthiller et al., 2013). The molecules exhibit unusual physicochemical behavior such as modified chromatographic behavior, which may be caused by the modification of an epitope recognized by antibodies used for detection. Besides, the behavior may change due to the effect of decreased extraction efficacy resulting from augmented polarity especially when a less polar solvent is used for the extraction of non-modified mycotoxins (Berthiller et al., 2013). The unavailability of commercial standards, also compounds the problem, making the identification and quantification of these compounds challenging. Consequently, the mycotoxin burden of screened food samples is underestimated when using conventional analytical techniques. Concerning the toxicological profiles of masked mycotoxins, the transformation processes that generate these compounds may significantly reduce their toxicity or lead to a total loss of toxicity. This reduction may be observed in situations where the molecules cannot be reactivated in the digestive tract of humans (Berthiller et al., 2013; Cirlini et al., 2012). Conversely, other modified forms of mycotoxins have been recognized to be partly or cleaved when passing through the gastrointestinal tract. Therefore, these forms may present the equivalent poisonous effects known for their parental mycotoxins. It is important to note that masked mycotoxins may also exhibit their toxicity, even though more research into their toxic potential is required (Cirlini et al., 2012; Gareis et al., 1990; Plasencia & Mirocha, 1991). Modifications of mycotoxins that reduce or eliminate toxicity may lead to an overestimation of mycotoxin contamination in tested food samples. This overestimation is since the modified mycotoxin is detected together with the unchanged mycotoxin, but it is not clarified that the analytical signal originated from a less toxic or non-toxic derivative. This is most pertinent for immunologic-based analytical approaches because epitopes recognized by antibodies and toxicity determinants destroyed by the modification may not be equal (Berthiller et al., 2013). Some studies presenting the techniques employed for detection of masked mycotoxins in cereal-based products are summarized in Table 2.

concentration of this mycotoxin in foods if its masked form can potentially be metabolized in the human body. Masked mycotoxins are mycotoxin derivatives which are generated via conjugation with sugars, amino acids, sulfate groups or other biological components (Berthiller, Dall'asta et al., 2009; Galaverna et al., 2009; Cirlini, Dall’Asta, & Galaverna, 2012; Rychlik et al., 2014). These modified mycotoxins are products of noncovalent, associative interactions between a ‘native’ mycotoxin and matrix macro constituents (Dall'Asta, Galaverna, Aureli, Dossena, & Marchelli, 2008; Dall'Asta, & Berthiller 2015). There are several mechanisms through which masked mycotoxins may emerge. They may be precursors, metabolites or degradation products of the ‘parent’ (or free) form of the mycotoxin, or they may be formed abiotically through chemical reactions of the parent toxin with the matrix (Dall'Asta et al., 2012). Masked mycotoxins may be further classified according to how the masked form relates to the parent form, in other words, whether the masked form exists as a covalent derivative of the parent toxin or the association between the parent toxin and matrix component is noncovalent. As metabolites, masked mycotoxins may originate from fungal, plants or mammalian metabolism. Certain mycotoxin conjugates are excreted directly by fungal species, although there is a paucity of data in this regard (Dall'Asta, & Berthiller 2015). The most common examples are 3acetyl deoxynivalenol (3-ADON) and 15-acetyl deoxynivalenol (15ADON) which have been detected in Fusarium-contaminated cereals (Berthiller, Schuhmacher, Adam, & Krska, 2009; Malachova et al., 2011). Both compounds ascend from 3,15-diacetyl deoxynivalenol (Kluger et al., 2013; Dall'Asta, & Berthiller 2015; Varga et al., 2015). The occurrence of 3-ADON and 15-ADON in cereals has been described in some studies (De Boevre et al., 2012; De Boevre et al., 2013; Nakagawa et al., 2011; Ok et al., 2011). Plants possess certain defense mechanisms which enable them to overcome or at least diminish the effects of xenobiotic compounds such as mycotoxins (Berthiller et al., 2013). Mycotoxin compounds are therefore converted into more polar metabolites that are carried into vacuoles for further storage or conjugated to cell wall components (Berthiller et al., 2013; Berthiller, Dall'asta et al., 2009; Berthiller, Schuhmacher et al., 2009; Gareis et al., 1990). Another mechanism through which mycotoxins may be chemically altered is via food production. Although mycotoxins are known for their thermal resistance, certain unit operations such as heating and fermentation have significant potential to modify mycotoxins (Dall’Asta, Galaverna, Dossena, Sforza, & Marchelli, 2009, pp. 385–397; Malacova et al., 2011; Berthiller et al., 2013; Karlovsky et al., 2016). Trichothecenes such as D3G have been found in malt and beer obtained from barley naturally infected with Fusarium (Kostelanska et al., 2009; Lancova et al., 2008). Oligoglycosides of DON, namely di-, tri- and tetra-glucosides, have also been detected in beer (Zachariasova, Vaclavikova, Lacina, Vaclavik, & Hajslova, 2012) and the occurrence of this compound in cereals has been confirmed as well. Further research regarding the modified forms of DON accumulated due to enzymes produced by starter cultures used for the production of beer and wine is highly desirable.

2.2.2. Incidence of masked form Only a few papers report the natural incidence of the modified forms of DON in wheat. Berthiller et al. (2005) analyzed five samples of wheat naturally contaminated with DON and its modified forms and obtained results ranging from 0.54 to 5.8, 0.05–0.20, < 0.01–0.5 and < 0.01–0.2 mg/kg for DON, DON- 3-glucoside, 3-ADON, and 15ADON, respectively. In a more recent study, Berthiller, Dall'asta et al., 2009, Berthiller, Schuhmacher et al., 2009 analyzed twenty-three samples of wheat from Austria, Germany, and Slovakia and found both DON and DON-3-glucoside in all analyzed samples ranging from 203 to 4130 ng/g and 76 and 1070 ng/g, respectively. A total of 359 wheat flour samples from China were analyzed by Li et al. (2016) and the results showed that DON was the most often detected mycotoxin (97.2%) while deoxynivalenol-3-glucoside (33.4%) was the third most frequent, with the average concentration in positive samples of 86.7 and 3.34 μg/kg, respectively. Nakagawa, He, Matsuo, Singh, and 15

Trends in Food Science & Technology 71 (2018) 13–24

Warth et al., 2015

Suman et al., 2013 Suman et al., 2013 Ovando-Martínez et al., 2013 Warth et al., 2015

Kostelanska et al., 2009 De Boevre et al., 2012

UPLC–TOFMS Waters Acquity UPLC-Quattro Premier XE MS LC–MS/MS LC–MS/MS LC and GC (LC-ESI)-MS/MS-based “dilute and shoot” (LC-ESI)-MS/MS-based “dilute and shoot”

UPLC-Orbitrap MS LCMS/MS

Berthiller, Dall'asta et al., 2009, Berthiller, Schuhmacher et al., 2009 Berthiller, Dall'asta et al., 2009, Berthiller, Schuhmacher et al., 2009 Kostelanska et al., 2011 Skrbic et al., 2011 LC-MS

LC-MS

Berthiller et al., 2005 Berthiller, Sulyok, Krska, & Schuhmacher, 2007 LCMS/MS LCMS/MS – – – –

References Method Of Measurement Limit of quantification (μg/ kg) Limit of detection (μg/ kg)

2

5

Fusarium species, chiefly F. graminearum and F. culmorum have a significant role in mycotoxin production in wheat and wheat-based products. Although both F. graminearum and F. culmorum seem to be able to infect cereals and cause FHB, F. graminearum is considered more virulent (Miller, 1995). FHB is prevalent in regions with excessive rain and mild temperatures (Wegulo, 2012), with its incidence being positively and linearly connected with DON concentrations in wheat (Wegulo, 2012). A visible characteristic of FHB is a mass of white or reddish spores that could be appeared in some parts of grains and finally affect commodity. A grain with youthful appearance can also be infected, particularly if the infection occurs at the end of grain development (Wegulo, 2012). The transporting of pathogens by seeds can be explained in different ways, for example, by contaminating the seeds either superficially or by colonizing their internal tissues. In this way, the ascospores of Fusarium can easily be dispersed over long distances (Kobayasti & Pires, 2011). It was demonstrated that both, F. graminearum ascospores and macroconidia can infect wheat (Miller, 1995). Ascospore dispersion has been associated with relatively high humidity, which, under favorable conditions, will result in macroconidia formation (Miller, 1995). Conversely, F. culmorum is widely distributed in soil, remaining viable for 2–4 years in the ground in the form of chlamydospores, which can penetrate seeds during germination through lesions in the root or stomas (Scherm et al., 2013). F. graminearum and F. culmorum produce different sets of metabolites, being classified into different chemotypes. Currently, the described four chemotypes for F. graminearum and F. culmorum can be summarized as NIV chemotype, which produces nivalenol and its acetylated forms; 3-ADON chemotype produces deoxynivalenol and 3acetyldeoxynivalenol, while 15-ADON chemotype produces deoxynivalenol and 15-acetyldeoxynivalenol (Ward, Bielawski, Kistler, Sullivan, & O'Donnell, 2002). A fourth chemotype (named “unknown”) refers to the species able to synthesize both NIV and DON (NIV/DON chemotype) (Quarta et al., 2006;; Ward et al., 2002). F. graminearum isolates may produce any of the four sets of metabolites (Ward et al.,

DON-3-Glc DON-3-Glc DON-3-Glc Deoxynivalenol-3-sulfate

Deoxynivalenol-15-sulfate

Bread Minicake Red Spring Wheat Wheat

Wheat

Austria

11 11 – 10 4 4 – 3

– 16 – 8 DON-3-Glc DON-3-Glc Malt Wheat

Italy Italy USA Austria

5 5 1 DON-3-Glc DON-3-Glc Wheat Wheat

Czech Republic Serbia and Czech Republic Czech Republic Belgium

10 4 DON-3-β-D-glucoside Maize

Austria

10 4 Austria Wheat

DON-3-glucosides Zearalenone-4-glucoside or DON-3glucoside DON-3-β-D-glucoside Wheat and maize Cereals

Austria Austria

Masked Mycotoxin

Country

Kushiro (2017) analyzed DON and its modified forms in wheat germplasm and found that DON concentration varied from 131 to 6337 ng/g while the DON-3-O-glucoside concentration ranged from 24 to 2683 ng/g. To comprehend the mechanism of production and to detect modified forms of DON, several papers analyze samples artificially infected by Fusarium spp. or DON and its precursors (Amarasinghe, Simsek, Brûlé-Babel, & Fernando, 2016; Berthiller et al., 2005; Nakagawa et al., 2017; Warth et al., 2015). A study with 84 samples of durum wheat in Argentina showed that all samples were positive for DON (average 1750 μg/kg), 94% for DON-3-glucoside (< LOQ-850 μg/ kg) and 49% for acetylated derivates of DON (< LOQ-190 μg/kg) (Palacios et al., 2017). Several modified forms of DON have been reported (Rychlik et al., 2014) such as 3-acetyl-DON (3-ADON), 15-acetyl-DON (15-ADON) and 3, 15-diacetyl-DON (3, 15-diADON), as DON acetyl derivatives. Deoxynivalenol-3-β-D-glucoside (DON-3-glucoside), DON-3-sulfate, DON15-sulfate, deoxynivalenol-15-β-d-glucopyranoside (DON-15-glucoside), DON-15-O-β-D-glucoside (D15G) and 15-acetyl-DON-3-sulfate (15-ADON3S) have also been reported as conjugated forms of DON (Warth et al., 2015; Suman, Bergamini, Castellani, & Manzitti, 2013; Rasmussen et al., 2012; Berthiller et al., 2005; Schmeitzl et al., 2015). Therefore, proper exposure and risk assessment models that will support decision-making should not only rely on the occurrence and quantification of food processing unit operations on DON but also on the modified forms of DON (acetyl derivatives and conjugated forms). Surely, the consideration of modified forms of DON in DON exposure and risk assessment models must be supported by previous studies on their relevance for public and animal health. 3. DON-producing fungi, FHB and Fusarium chemotypes

Product

Table 2 Some of the used techniques for detection of masked mycotoxins in cereal based products.

A.M. Khaneghah et al.

16

Trends in Food Science & Technology 71 (2018) 13–24

A.M. Khaneghah et al.

Table 3 Incidence of DON in wheat and wheat-based products.a Matrix

N (n)

Country

Year

Method

LOD (μg/Kg)

LOQ (μg/ Kg)

Mean (range) μg/Kg

Reference

Wheat

113 (75)

Brazil

ic-ELISA

177.1

–

1894.9 (206.3–4732.3)

Dos Santos et al., 2013

Wheat

41 (24)

South Korea

HPLC

2.2

4.4

32.7 (14.3–353.6)

Ok et al., 2009

Wheat Wheat Wheat

57 (16) 51 (33) 81 (9)

Italy Croacia Marrocos

2008/ 2009 2007/ 2008 – – –

LC-MS/MS ELISA LC

5 20.5 13

10 – 40

10.96 (9.6–99.6) 223 (115–278) 502.1 (ND - 1310)

Wheat Wheat Wheat Wheat Wheat Pizza Vienna Bread French Bread Sliced Bread Bread Bread Bread

96 (81) 152 (125) 147 (104) 26 (19) 26 (5) 8 46 64 72 (12) 31 (31) 75 (21) 9 (3)

Germany Slovakai Slovakai Romania Romania Argentina Argentina Argentina Spain Spain Spain China

GC-MS ELISA ELISA ELISA ELISA GC GC GC LC-DAD GC-MS GC-MS GC-ECD

1 200 200 110 110 6.9 4 4 – – 7.3 8

– – – 220 220 13.8 8 8 30 18 12.2 21

1632 (4–20538) 930 300 2263.1 (294–3390) 763.6 (254–1440) (8–85) (5–149) (7–271) 68 246 42.5 (ND-146.6) 1860 (750–3450)

Juan, Ritieni, & Mañes, 2013 Pleadin et al., 2013 Ennouari, Sanchis, Marín, Rahouti, & Zinedine, 2013 Müller & Schwadorf, 1993 Sliková et al., 2013 Sliková et al., 2013 Alexa et al., 2013 Alexa et al., 2013 Pacin, Resnik, & Martinez, 2011 Pacin et al., 2011 Pacin et al., 2011 Cano-Sancho et al., 2013 Cano-Sancho et al., 2013 Gonzáles-Osnaya et al., 2011 Fan, Zhang, Zhou, Chen, & Wang, 2009

Bread

8 (3)

South Korea

HPLC

2.2

4.4

19.6 (37.5–78.1)

Ok et al., 2009

Bread Pasta Pasta Pasta Pasta

101 (93) 12 70 (52) 75 (47) 23 (19)

Germany Argentina Spain Spain China

GC-MS GC GC-ECD GC-MS GC-ECD

7 3.1 – 6.1 8

23 6.2 42 9.1 21

155 (15–690) 79 226 137.1 (10.9–623.3) 2360 (70–7520)

Schollenberger et al., 2005 Pacin et al., 2011 Cano-Sancho et al., 2013 Gonzáles-Osnaya et al., 2011 Fan et al., 2009

Wheat flakes Wheat flour

27 (20) 37 (16)

Spain South Korea

GC HPLC

– 2.2

41 4.4

190 18.8 (3.1–172.9)

Cano-Sancho et al., 2013 Ok et al., 2009

Wheat bran Bolo

37 (23) 6 (3)

Spain China

HPLC GC-ECD

100 8

300 21

1463 (ND - 6178) 620 (170–1350)

Vidal, Marín, Ramos, Cano-Sancho, & Sanchis, 2013 Fan et al., 2009

Cookies Cookies

26 36 (29)

Argentina China

GC GC-ECD

2.8 8

5.6 21

(11–85) 2790 (80–11380)

Pacin et al., 2011 Fan et al., 2009

Cookies

8 (3)

South Korea

HPLC

2.2

4.4

9.4 (22.6–35.2)

Ok et al., 2009

1987 2010 2011 2010 2011 – – – – – – 2006/ 2007 2007/ 2008 1999 – – – 2006/ 2007 – 2007/ 2008 2012 2006/ 2007 – 2006/ 2007 2007/ 2008

a Non-available; N: number of samples; n: number of positive samples; LOD: limit of detection; LOQ: limit of quantification; CG: gas chromatography; ECD: electron capture detector; MS: mass spectrometry; LC: liquid chromatography; DAD: diode array detector; HPLC: High-performance liquid chromatography; ELISA: enzyme linked immune sorbent assay.

Aldred, & Magan, 2005; Pitt & Hocking, 2009). Nevertheless, the adaptation of F. graminearum to lower temperatures due to genetic modifications or climatic changes has been reported (Scherm et al., 2013). In contrast, F. culmorum can grow at a temperature up to 0 °C, with an optimum growth about 25 °C. The minimum water activity (aw) for growth is 0.87 at 20–25 °C and pH 6.5 (Sanchis & Magan, 2004). Other relevant factors affecting DON production include temperature and moisture. F. graminearum and F. culmorum can grow and produce DON optimally at 25 °C Hope et al. (2005). Despite this, F. graminearum seems to be more competitive, presenting a faster growth rate and a greater tolerance for growth in a larger aw range. The minimal aw for DON production by F. graminearum and F. culmorum is 0.9 (Pitt & Hocking, 2009). DON is synthesized through the condensation of three units of mevalonate originating from trans-farnesyl pyrophosphate (FPP) that undergo cyclization to produce tricodiene, the precursor of trichothecenes (Blackwell, Miller, & Greenhalgh, 1985). Fifteen genes located at three loci on diverse chromosomes encode the involved enzymes and regulatory proteins in DON biosynthesis. A group of 12 Tri genes is placed at one locus, whereas Tri1-Tri16 and Tri101 are located at the remaining loci (Merhej, Richard-Forget, & Barreau, 2011). For DON biosynthesis, the Tri5 gene encodes trichothecene synthase, which catalyzes the reaction required to form trichothecene which followed by nine performed reactions by encoded enzymes by the Tri4, Tri101,

2002), while F. culmorum produces DON or nivalenol and their acetylated forms (Pitt & Hocking, 2009). The different chemotypes may occur in the same geographical site; however, finally one of them will be the predominant (Panthi, 2012). Besides, geographic distribution regarding the occurrence of chemotypes seems to be dependent upon the continent and even regions within a country (Panthi, 2012). Seasonal variations regarding the incidence/predominance of the different chemotypes of Fusarium have also been described (Jennings, Coates, Turner, Chandler, & Nicholson, 2004). The information of the chemotype occurring in a region is crucial due to observed differences toxicological between DON and NIV (Desjardins & Proctor, 2007), as well as fungi aggressiveness for plant infection (Panthi, Hallen-Adams, Wegulo, Hernandez Nopsa, & Baenziger, 2014). This knowledge might also be crucial considering the risk management strategies to be applied aiming to lessen human and animal exposure to DON and its modified forms.

4. DON biosynthesis and important factors in DON production by Fusarium Environmental and genetic features are involved in the forming of mycotoxins by fungi. With an optimum growth temperature of 25 °C and minimum growth temperatures ranging from 0.9 to 15–25 °C, F. graminearum is a common species in warm climates (Hope, 17

Trends in Food Science & Technology 71 (2018) 13–24

A.M. Khaneghah et al.

Employing of isolated microorganisms in order to prevent saprophytic growth and further perithecial developments by the pathogen is another proposed strategy. In this regard, 354 bacterial strains were evaluated in two selection steps using an index of dominance (ID) assay considering environmental parameters such as temperature and water activity in the interaction between pathogen and antagonist. Among them, 22 strains (6%) were able to reduce the growth of F. graminearum, which caused a reduction in the production of DON on irradiated wheat grains by 60–100% (Palazzini, Ramirez, Torres, & Chulze, 2007). Due to adverse effects of high moisture, which can facilitate fungal infection of wheat, the high occurrence of rain during flowering can lead to increase of DON concentrations in wheat. Planting wheat subsequently to crops other than maize as an appropriate strategy decreased the DON concentration to 33 ± 11% compared with maize as the pre-crop. Also approaching a moldboard plow, the DON concentration was diminished to 33 ± 7% in comparison with minimal or no-tillage plots. A decrease in DON content (24 ± 7%) was noted when using moderately vulnerable cultivars compared to susceptible cultivars. So, the particular choice of the variety can be assumed as the most efficient agronomic approach to reducing the DON concentration in wheat. This method can be followed by plowing, using other crops than maize as pre-crop and applying triazole fungicides at wheat anthesis (Beyer, Klix, Klink, & Verreet, 2006). Moreover, the concentration of DON can be reduced by 97% at most favorable agricultural practices (plowing, moderately resistant variety, triazole application at heading) in comparison with the worst scenario (direct sowing, susceptible variety, no fungicide application) (Blandino et al., 2012; Pitt, Taniwaki, & Cole, 2013). The time course of DON production and control at the pre-harvest, post-harvest, storage, and processing steps of wheat was recently illustrated by Pitt et al. (2013) (Fig. 3). Fig. 3 shows that while mycotoxin production can take place at pre- and post-harvest steps, levels of DON will remain unaltered during storage and will be reduced if proper procedures are adopted during wheat processing (Fig. 3). At the postharvest step, reducing the aw to less than 0.9 through quick drying can be useful in avoiding an increase in DON concentration. On the other hand, slow drying can provide conditions for growth of Fusarium and the increase in the concentration of DON will be observed. The procedures that can assist in reducing DON levels in wheat include cleaning of wheat grains, removal of immature, seared or roasted grains, other seeds, sand, chaff, and stones (Webb & Owens, 2003). During this step of processing, the concentration of DON can be reduced by visual inspection (FHB-contaminated grains are pink), whereas chemical analysis may facilitate deciding whether to reject batches of wheat (Pitt et al., 2013) (Fig. 3). Different types of equipment can be used for cleaning and be sorting wheat. The features of the grain, such as the shape, size, thickness, and extent of resistance to air are the criteria considered in this step of wheat processing (Cheli, Pinotti, Rossi, & Dell'Orto, 2013). Grains contaminated by Fusarium are less thick than uninfected grains and can be easily separated by gravitational sorting (Hazel & Patel, 2004). The application of optical-based methods for evaluation of morphological and colorimetric characteristics of wheat grains can improve the efficiency of this step of wheat processing. A high-speed optical sorting method can be useful for sorting wheat when DON levels are 2–5.7 mg/kg (Delwiche, Pearson, & Brabec, 2005). After cleaning, wheat grains are conditioned, which can be valued as one of the most critical stages in wheat is processing from the technological point of view. The addition of water increases the moisture concentration of the grains, and the wheat is allowed to settle for a period. This step improves the efficiency of flour extraction through the simplification of physical separation of endosperm and bran (Posner & Hibbs, 1999). Despite the increase of water content of grains during this step, conditioning does not seem to constitute a step adequate for fungi growth and DON production. The next step in wheat processing aims to separate particles

Tri11 and Tri3 genes, resulting in the formation of various precursors of DON (Alexander, Proctor, & McCormick, 2009). An acidic pH can be regarded as a key environmental feature that induces DON biosynthesis. The reduction of the pH can occur as result of the consumption of available nitrogen-containing compounds in food or the culture medium, leading to the formation of ammonium. This condition induces the expression of the Tri5 gene product, which is responsible for FPP cyclization, which will result in the formation of tricodiene, a precursor of DON (Merhej, Boutigny, Pinson-Gadais, Richard-Forget, & Barreau, 2010). DON biosynthesis is also induced as a response to plant defense mechanisms to infection by fungi (Jansen et al., 2005). DON synthesis by F. graminearum enables the diffusion of fungi from an infected branch to a healthy branch through the formation of hyphae. Furthermore, the toxin prevents the thickening of plant cell wall, which would serve as a barrier for fungal penetration (Jansen et al., 2005). 5. Incidence of DON in wheat and wheat-based products The collected data regarding the frequency of DON in wheat and wheat-based products are shown in Table 3. DON has been found in different types of raw materials as well as products such as wheat, pizza, bread, pasta, cookies, bran, and flour. In general, wheat was found to carry higher levels of DON when compared with wheat-based products. These data highlight how stable DON is to wheat and wheatbased products processing and depict the importance of preventative strategies applied in the field and also before processing to diminish human exposure to DON. As seen in Table 3, the concentration of DON in samples collected in several countries varied from below the limit of detection (LOD)/limit of quantification (LOQ) of analytical methods used up to level as high as 11380 μg/kg. The most commonly used methods to determine the concentration of DON are High-performance liquid chromatography (HPLC), gas chromatography coupled with mass spectrometry (CG-MS) and liquid chromatography coupled to mass spectrometry (LC-MS) (Table 3) in addition to and immuno-enzymatic methods. The ELISA (enzyme-linked immunosorbent assay) is the main immuno-enzymatic technique used for the detection and determination of the concentration of this mycotoxin. Although these methods have advantages and limitations while applied to DON detection and quantification, it should be reinforced that a thorough discussion and critical assessment of these aspects is out of the scope of this review. Thus, Table 2 is presented herein aiming to highlight the widespread occurrence and levels of DON in wheat and wheat-based products. 5.1. Incidence of DON in wheat and preventive measures Wheat is a gramineous plant of the Triticum group, belonging to the Poaceae family and the Pooideae subfamily. Wheat is an annual plant cultivated during winter or spring (Scheuer, de Francisco, de Miranda, & Limberger, 2011). The amount of DON present in wheatbased products is mainly reliant on the initial concentration of this mycotoxin in wheat, which can correlate with weather and crop rotation at the pre-harvest stage. Several types of mycotoxigenic fungi could infect plant hosts which can be resulted in some diseases in the field. However, highly resistant wheat cultivars for reducing FHB currently are not well developed, and labeled fungicides are not consistently effective (Schisler, Khan, & Boehm, 2002), the preventive controlling of infection in the field still is a critical step in managing of mycotoxin production in the harvested product. Some of the recently introduced strategies such as fungicides and biological control agents can be applied in order to protect flowering heads from further infections. Also, introducing of exogenous traits to implant into cereals to enhance resistance is another solution. Additionally, cultural practices are also being approached as measures to reduce pathogen survival and inoculum production in crop residues (Yuen & Schoneweis, 2007). 18

Trends in Food Science & Technology 71 (2018) 13–24

A.M. Khaneghah et al.

achieved (flour or semolina); while the most concentration of DON is transferred to, the animal feed fractions (bran, middlings, and shorts). In this context, the lower DON levels in processed flour might be associated with the physical barrier properties of the bran layer in order to prevent the mycelia from further penetrating into the kernel. Generally speaking, milling causes a decline of the DON levels in the final flour or semolina, while an increase of DON concentration in the external parts of wheat grains (bran and shorts) is noted (Vidal, Sanchis, Ramos, & Marín, 2016). Moreover, the contaminated kernels by deoxynivalenol was removed by the use of gravity separators, reducing moisture as well as inoculum during storage. However, such process like separation of shriveled kernels and washing of grain was considered as eliminating steps up to 74% of deoxynivalenol, milling caused a higher concentration of deoxynivalenol in bran and shorts, and in lower concentrations of DON in straight-grade flour. Also, the distribution of DON in the different obtained fractions from wheat milling were correlated to the degree of fungal penetration inside of the endosperm, which was related to the type of wheat cultivar. (Milani & Maleki, 2014). Also, a similar condition was noted regarding the ochratoxin A among milling process of whole wheat grains (Scudamorey et al., 2009). In one conducted study, DON and D3G contaminated wheat samples at five different levels were milled. Mycotoxin levels in milling fractions, doughs and CSB (Chinese steamed bread) were evaluated using UPLC-MS/MS. Concentrations of DON and D3G in bran were measured as 1.2–2.2 times, 2.9–4.4 times higher than wheat grain, and slightly lower in shorts while compared to bran. In another word, a decline of 23–39% for D3G in flour and 79–90% for DON were reported, respectively, compared to wheat grain. With considering to wheat grain, the distribution of DON was 9% in flour, 27% in shorts 35% in bran. Although, the distribution of D3G was recorded as 37% in flour, 58% in shorts, 77% in bran. As an overall observation, however, the milling resulted a decrease in the total amount of DON; the concentration of D3G (resulted from the binding of DON to starch during the milling process) was increased (Zhang & Wang, 2014). In another investigation, the distribution of DON in the wheat kernel, as well as the effect of exposure time to ozone on DON removal, were investigated. The degradation rates of DON as were noted as 26.40%, 39.16%, and 53.48% after exposing of the samples to 75 mg/L ozone for 30, 60, and 90 min, respectively. Also, considering the results of quality and nutrition evaluation produced wheat flour, among the control samples and ozone-treated samples, in terms of protein content, fatty acid value, amino acid content, starch content, carbonyl and carboxyl content, and swelling power no significant differences (P > 0.05) were observed. Moreover, higher tenacity and whiteness, as well as lower extensibility and yellowness were noted in ozonetreated samples. Based on the results, DON levels can be reduced by using the ozone treatment technology while flour quality can be improved (Wang et al., 2016).

according to their differences in size, resistance to air and density. The purification system is composed of purifiers, mills, and sieves, with the particles being classified as pure or intermediate. The flour considered pure is submitted to the reduction system, whereas the intermediate flour will be processed in mills, resulting in the separation of large amounts of endosperm and bran (Webb & Owens, 2003). The white flour can be obtained at the end of the reduction process. The reduction system consists of mills and sieves arranged in series, through which the particles pass eleven times (Posner & Hibbs, 1999). In the final step of processing, any particles that pass through the flat sieves are considered white flour, whereas those retained are returned to the system for additional processing (Webb & Owens, 2003). The importance of these operations for wheat contamination by DON relies on the fact that the distribution of this mycotoxin in the grains is not uniform. It is known that the outer parts of the grain present a high contamination level, whereas lower concentrations are found in the endosperm (Abbas, Mirocha, Pawlosky, & Pusch, 1985). However, because of the processing features, the initial concentration of DON is reduced during milling, with lesser amounts being found in the flour, which is the fraction that derives from the most internal part of wheat (IsraelRoming & Avram, 2010). The lipidic fractions of wheat, such as the germ and germ oil, are not significant sources of DON (Giménez et al., 2013). However, the bran is the wheat fraction most heavily contaminated with DON (Abbas et al., 1985), which represents a significant concern because this fraction is widely employed to produce feed for animals as well as ingredient raw material for food formulations. After the wheat has been milled, the flour has a lower concentration of DON, whereas the bran can carry high levels of this mycotoxin. Regarding the different types of flours, the DON concentration is reduced correspondingly in wholemeal flour and white flour. However, the initial level of contamination of wholemeal flour tends to be greater than that of white flour, emphasizing the requirement to control the initial concentration of DON in wheat within the range defined by legislation (Scudamore, Hazel, Patel, & Scriven, 2009). Even though during milling a decline in DON concentrations can take place during milling, the range of reduction can be affected by the location of this mycotoxin in the grains. The deeper the mycotoxin in the grains, the lower the impact of milling on DON in the flour (Young, Fulcher, Hayhoe, Scott, & Dexter, 1984). The conjugated form of DON, deoxynivalenol-3-glycoside (DON-3Glc) (a masked form of DON), has been found in wheat and in milling fractions (white flour and bran) in relative molar ratios (DON-3-Glc/ DON) of 6.3–22.7, 7.2–23.2 and 6.9–16.7 mol %, respectively (Kostelanska et al., 2011). 6. The fate of DON during wheat milling, bread, and pasta processing A scheme depicting the main steps of wheat, bread and pasta production is presented in Fig. 2 to allow a better assessment of the fate of DON during of wheat, bread, and pasta production. It should be highlighted that the details of bread and pasta production steps with no reported impact on DON concentration will be disregarded from this review.

6.2. Bread Although bread processing involves weighing and mixing of all ingredients to produce a smooth dough, followed by fermentation and baking (Haegens, 2006), impacts on DON contents have only been reported for last two steps because both involve biochemical reactions and temperature shifts. The fermentation process changes the dough in two aspects: first, the yeast converts the carbohydrates to form of carbon dioxide, which expands the volume of the mass as well reducing the pH value. Then, enzymatic hydrolysis softens the gluten, enabling greater gas retention so that the desired volume is reached (Yang, 2006). The fermentation process can occur through the mixing of the dry ingredients with the subsequent incorporation of water until the dough reaches the expansion stage (linear process) (Curic, Novotni, & Smerdel, 2013). Subsequently, fat and oil are mixed in until the dough is completely

6.1. Wheat milling Due to the high concentration of DON in raw wheat, investigation regarding the stability of DON during food processing is the point of interest. Almost, more than half of harvested wheat in the world is subjected to the milling process. In this regard, several studies have been carried out considering the effect of wheat milling on the DON reduction. However, DON is not totally removed during milling; it is only redistributed and again re-concentrated in specific milling fractions. Therefore, as result of DON-contaminated wheat milling, less contaminated fractions intended for human consumption can be 19

Trends in Food Science & Technology 71 (2018) 13–24

A.M. Khaneghah et al.

Fig. 2. Steps of wheat processing.

Wheat

Cleaning and selection

Conditioning and Fragmentation Wheat Bran

Dirty materials

Purification System

Reduction System

Flour

Mixing the Dough

Mixing the Ingredients

Fermentation

Rolling

Baking

Cutting and Drying

Bread

Pasta

2013; Samart et al., 2001; Valle-Algarra et al., 2009; Young et al., 1984). For instance, fermenting the dough at approximately 30 °C did not affect the DON concentration (Valle-Algarra et al., 2009). In contrast, a reduction in the DON content (to 41% of the initial concentration of DON in the dough) was reported when the dough was fermented at higher temperatures (50 °C for 40 min) (Samar, Neira, Resnik, & Pacin, 2001). An increase in DON concentration compared to the initial concentration in the dough immediately before fermentation was reported (Bergamini et al., 2010; De Angelis, Monaci, Pascale, & Visconti, 2013; Young et al., 1984). Data regarding the impact of fermentation on decrease or increase in DON concentration must be carefully assessed due to the formation of conjugated mycotoxin (masked), it would not be available for quantification (Pereira, Fernandes, & Cunha, 2014). Therefore, if no proper analytical approach for quantification of the masked mycotoxin is employed, contradictory

homogeneous. The appropriate temperature for fermentation was 27 °C, with a relative moisture value of 75%, and fermentation time varying from 1.5 to 3 h (Yang, 2006). The sponge method involves two mixing stages: first, pre-fermentation occurs after part of the flour; water and yeast have been mixed to form sponges. Then, more flour and a portion of the sugar are incorporated, which completes the first stage. In the second stage, the other ingredients are combined, and fermentation itself occurs (Yang, 2006). The fate of DON during one of the most important steps of bread making, i.e., the fermentation, has been reported in the literature, while different results have been obtained. Overall, no studies have compared the impact of different processing methods of bread on DON levels. However, data in the literature are conflicting indicating reduction, increase or stability of DON during dough fermentation for bread making (Bergamini et al., 2010; Cano-Sancho, Sanchis, Ramos, & Marín,

Fig. 3. Formation and reduction of DON in wheat on preharvest, post-harvest, storage and processing stages. (Pitt et al., 2013; with permission).

20

Trends in Food Science & Technology 71 (2018) 13–24

A.M. Khaneghah et al.

6.3. Pasta

results can be obtained. In addition to the presence of masked forms of DON, another possible cause of the increase in the DON content after dough fermentation is the action of yeasts. Young et al. (1984) suggested that this increase occurs due to the conversion of DON precursors that are present in flour to DON by yeasts. To date, these precursors have not been identified or quantified. Quantification of DON precursors and masked forms of DON is important in elucidating the effects of dough fermentation on the levels of this mycotoxin in the final product. In another study, the fate of deoxynivalenol (DON) and deoxynivalenol-3-glucoside (D3G) among Chinese steamed bread (CSB) processing was studied. The concentration of DON approximately doubled while the mixed and fermented dough was processed into CSB. However, D3G levels in mixed and fermented doughs as well as in CSB did not differ significantly, were almost reduced about 50% in flour. Additionally, dough-making procedure caused a decrease in the concentration of D3G and the level of DON was increased by steaming process. Therefore, CSB processing may increase the concentration of DON in bread as result of releasing bound DON in flour (Zhang & Wang, 2014). The relative molar DON-3-Glc/DON ratio in kneaded and fermented dough has been found to vary between 8.1-25.7 and 9.0–20.6 mol%, respectively (Kostelanska et al., 2011). The relative molar DON-3-Glc/ DON ratio in wheat samples that were highly infected with Fusarium was lower, suggesting that the glycosylation capacity of DON in these grains was limited. Another less common form of conjugated DON is the acetylated DON, which may be present in levels as low as five μg/Kg (Kostelanska et al., 2011). Furthermore, the addition of bread improvers (enzyme preparations applied with the objective of improving the rheological parameters of the dough and the quality of the bakery products) during fermentation did not affect the DON contents of the dough. In contrast, adding such enzyme preparations to the dough to different final concentrations significantly increased (up to 145%, in average) the content of DON-3-Glc (Kostelanska et al., 2011). The baking is another step of bread making in which could alter the content of DON in the final product. During baking, the appearance of the dough is changed by heat due to chemical, physical and biological transformations. However, the used oven temperature as well as the duration of the baking process could be vary based on the size and type of dough, this process involves high temperatures, such as 170–350 °C. Additionally, although DON is considered to be resistant to such high temperatures (Sobrova et al., 2010), the reported reduction in the concentration of DON can be associated with other factors, such as the used strain of yeast, the baking period, the size of the bread and other ingredients. Likewise, the addition of the reducing agent's sodium bisulfite, L-cysteine, and ammonium phosphate into the dough formulation significantly reduced the DON concentration in baked bread (Boyacioglu, Heltiarachchy, & D’appolonia, 1993). Additionally, the detection of lower levels of DON after baking the bread might also be related to the conjugation of this mycotoxin with the food matrix rather than its degradation (Valle-Algarra et al., 2009). During the baking step, the concentration of the conjugated forms of DON (DON-3-Glc) is reduced, whereas the concentration of DON increases (De Angelis et al., 2013), which suggests that the breakdown of DON conjugation is promoted during this step. Despite these presented results, the expected result is no change in the DON concentration after baking due to the resistance of this mycotoxin to thermal processing (Cano-Sancho et al., 2013). Turner, Burley et al., 2008; Turner, Rothwell et al., 2008 quantified the DON content of the urine of individuals who consumed wheat-based products and found this mycotoxin in 98.7% of the samples. Wholemeal bread was considered the food that most contributed to the presence of DON in urine, although DON was also detected in the urine of individuals who consumed bread made with white flour and pasta. In another study, it was shown that a limited consumption of wheat-based products led to a diminution in the DON concentrations in urine (Turner, Burley et al., 2008; Turner, Rothwell et al., 2008).

Pasta processing involves a series of unit operations, including homogenization of dry ingredients (flour and additives) with the liquid ingredients (water and eggs), past cut, drying and further cooking (ElDash & Germani, 1994; Guerreiro, 2006). Despite this, only cooking seems to have an impact on DON contents in pasta. As DON is a watersoluble mycotoxin, during cooking, it can be transferred from the dough to the cooking water, which will be afterward discharged. The reduction of the DON contents in cooked pasta ranges from 60 to 75% as compared to the contents of the dry pasta (Brera et al., 2013; CanoSancho et al., 2013; Gonzáles-Osnaya et al., 2011; Visconti, Haidukowski, Pascale, & Silvestri, 2004). Regardless of the effects reported in the literature, it should be highlighted that variability in the reduction of DON by cooking can occur due to several factors such as cooking time, temperature, water/pasta proportion, among others. 7. Concluding remarks The wheat and wheat-based products, such as bread and pasta, could play a chief role in the human exposure to DON. Thus, accurate data on the prevalence of FHB in wheat as well as on the incidence of DON in wheat grains comprises primarily relevant information to assess and avoid human exposure to this mycotoxin. The applied preventive strategies among the pre- and post-harvest stages can be recognized as the most useful tools to control of the occurrence of DON in wheat and wheat-based products. Avoiding plant infection by Fusarium species, managing crops and ensuring the rapid drying of wheat after harvest are very effective approaches for reducing the DON contamination of this grain. In comparison with un-milled grain, the flour has a lower concentration of DON. Moreover, the reduction of DON concentration was similar in wholemeal flour and white flour. However, the initial level of contamination of wholemeal flour tends to be greater than that of white flour. The differences in processing, such as temperature, additives, processing time and loaf size are the effective factors in contradictory reports available of the literature. Also, further studies must be conveyed aiming to reveal the role of modified forms of DON as one of the reasons for the observed contradictory reports in the literature. These compounds can be formed throughout wheat processing, from pre-harvest to processing of wheat-based products, and for proper quantification, analytical methods able to quantify modified forms of DON are needed. Given the above, the development of methods to quantify modified forms of DON is the first step towards a better characterization of the hazard (DON and its modified forms). Further, the establishment of health effects due to exposure to DON modified forms is highly relevant to enhance the awareness of the health impact of these mycotoxins. That will further allow refinement of risk assessment models that can be used to generate scientific-based intervention strategies to protect animal and human health. Acknowledgements The authors are thankful to Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq) (Grant # 302763/2014-7), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) (Grant # 33003017027P1). Amin Mousavi Khaneghah wishes to thank the support of CNPq-TWAS Postgraduate Fellowship (Grant # 3240274290). References Abbas, H. K., Mirocha, C. J., Pawlosky, R. J., & Pusch, D. J. (1985). Effect of cleaning, milling, and baking on deoxynivalenol in wheat. Applied and Environmental Microbiology, 50, 482–486. Alexa, E., Dehelean, C. A., Poiana, M. A., Radulov, I., Cimpean, A. M., Bordean, D. M., et al. (2013). The occurrence of mycotoxins in wheat from western Romania and histopathological impact as effect of feed intake. Chemistry Central Journal, 7(1), 99. Alexander, N. J., Proctor, R. H., & McCormick, S. P. (2009). Genes, gene clusters, and

21

Trends in Food Science & Technology 71 (2018) 13–24

A.M. Khaneghah et al.

based foods in Belgium. Toxicology Letters, 218(3), 281–292. Delwiche, S. R., Pearson, T. C., & Brabec, D. L. (2005). High-speed optical sorting of soft wheat for reduction of deoxynivalenol. Plant Disease, 89, 1214–1219. Desjardins, A. E., & Proctor, R. H. (2007). Molecular biology of Fusarium mycotoxins. International Journal of Food Microbiology, 119, 47–50. El-Dash, A., & Germani, R. (1994). Tecnologia de farinhas mistas: Uso de farinhas mistas na produção de massas alimentícias. Brasília: EMBRAPA-SPI, 5, 38. Embrapa-Trigo. Available at: http://www.cnpt.embrapa.br/, Accessed date: 21 October 2016. Ennouari, A., Sanchis, V., Marín, S., Rahouti, M., & Zinedine, A. (2013). Occurrence of deoxynivalenol in durum wheat from Morocco. Food Control, 32(1), 115–118. European Food Safety Authority (2013). Deoxynivalenol in food and feed: Occurrence and exposure. EFSA Journal, 11(10), 3379. Fan, P., Zhang, Y., Zhou, M., Chen, C., & Wang, J. (2009). Incidence of trichothecenes in wheat-based foods from China. International Journal of Environmental Analytical Chemistry, 89(4), 269–276. http://doi.org/10.1080/03067310802635570. Filtenborg, O., Frisvad, J. C., & Thrane, U. (1996). Moulds in food spoilage. International Journal of Food Microbiology, 33, 85–102. Foroud, N. A., & Eudes, F. (2009). Trichothecenes in cereal grains. International Journal of Molecular Sciences, 10, 147–173. Galaverna, G., Dall'Asta, C., Mangia, M., Dossena, A., & Marchelli, R. (2009). Masked mycotoxins: An emerging issue for food safety. Czech Journal of Food Science, 27, 89–92. Gareis, M., Bauer, J., Thiem, J., Plank, G., Grabley, S., & Gedek, B. (1990). Cleavage of zearalenone-glycoside, a “masked” mycotoxin, during digestion in swine. Journal of Veterinary Medicine, Series B, 37(1–10), 236–240. Gärtner, B. H., Munich, M., Kleijer, G., & Mascher, F. (2008). Characterisation of kernel resistance against Fusarium infection in spring wheat by baking quality and mycotoxin assessments. European Journal of Plant Pathology, 120(1), 61–68. Generotti, S., Cirlini, M., Malachova, A., Sulyok, M., Berthiller, F., Dall'Asta, C., et al. (2015). Deoxynivalenol & deoxynivalenol-3-glucoside mitigation through bakery production strategies: Effective experimental design within industrial rusk-making technology. Toxins, 7(8), 2773–2790. Giménez, I., Herrera, M., Escobar, J., Ferruz, E., Lorán, S., Herrera, A., et al. (2013). Distribution of deoxynivalenol and zearalenone in milled germ during wheat milling and analysis of toxin levels in wheat germ and wheat germ oil. Food Control, 34, 268–273. González-Osnaya, L., Cortés, C., Soriano, J. M., Moltó, J. C., & Mañes, J. (2011). Occurrence of deoxynivalenol and T-2 toxin in bread and pasta commercialized in Spain. Food Chemistry, 124, 156–161. Guerreiro, L. (2006). Dossiê técnico: Massas alimentícias. Rede de Tecnologia do Rio de Janeiro – REDETEC. Haegens, N. (2006). Mixing, dough making, and dough makeup. In Y. H. Hui, H. Corke, I. D. Leyn, W.-K. Nip, & N. Cross (Eds.). Bakery products science and technology (pp. 261– 271). Ames: Blackwell Publishing. Hazel, C. M., & Patel, S. (2004). Influence of processing on trichothecene levels. Toxicology Letters, 153, 51–59. Hope, R., Aldred, D., & Magan, N. (2005). Comparison of environmental profiles for growth and deoxynivalenol production by Fusarium culmorum and F. graminearum on wheat grain. Letters in Applied Microbiology, 40, 295–300. International Agency for Research on Cancer (IARC). (1993). Available at: http://www. iarc.fr/. Accessed on 18 September 2016. Iordanov, M. S., Pribnow, D., Magun, J. L., Dinh, T., Pearson, J. A., Chen, S. L., et al. (1997). Ribotoxic stress response: Activation of the stress-activated protein kinase JNK1 by inhibitors of the peptidyl transferase reaction and by sequence-specific RNA damage to the α-sarcin/ricin loop in the 28S rRNA. Molecular and Cellular Biology, 17, 3373–3381. Israel-Roming, F., & Avram, M. (2010). Deoxynivalenol stability during wheat processing. Romanian Biotechnological Letters, 15, 47–50. Jansen, C., Von Wettstein, D., Schäfer, W., Kogel, K., Felk, A., & Maier, F. J. (2005). Infection pattern in barley and wheat spikes inoculated with wild-type and trichodiene synthase gene disrupted Fusarium graminearum. Proceedings of the National Academy of Sciences of the United States of America, 102, 16892–16897. Jennings, P., Coates, M. E., Turner, J. A., Chandler, E. A., & Nicholson, P. (2004). Determination of deoxynivalenol and nivalenol chemotypes of Fusarium culmorum isolates from England and Wales by PCR assay. Plant Pathology, 53, 182–190. JOINT FAO/WHO expert committee on food Additives (Vol. Ed.), (2011). WHO Technical Report Series: Vol. 959, (pp. 37–48). Jones, H. D. (2005). Wheat transformation: Current technology and applications to grain development and composition. Journal of Cereal Science, 41, 137–147. Juan, C., Ritieni, A., & Mañes, J. (2013). Occurrence of Fusarium mycotoxins in Italian cereal and cereal products from organic farming. Food Chemistry, 141(3), 1747–1755. Karlovsky, P., Suman, M., Berthiller, F., De Meester, J., Eisenbrand, G., Perrin, I., et al. (2016). Impact of food processing and detoxification treatments on mycotoxin contamination. Mycotoxin Research, 32(4), 179–205. Kluger, B., Bueschl, C., Lemmens, M., Berthiller, F., Häubl, G., Jaunecker, G., et al. (2013). Stable isotopic labelling-assisted untargeted metabolic profiling reveals novel conjugates of the mycotoxin deoxynivalenol in wheat. Analytical and Bioanalytical Chemistry, 405(15), 5031–5036. Kobayasti, L., & Pires, A. P. (2011). Levantamento de fungos em sementes de trigo. Pesquisa Agropecuaria Tropical, 41, 572–578. Kostelanska, M., Dzuman, Z., Malachova, A., Capouchova, I., Prokinova, E., Skerikova, A., et al. (2011). Effects of milling and baking technologies on levels of deoxynivalenol and its masked form deoxynivalenol-3-glucoside. Journal of Agricultural and Food Chemistry, 59, 9303–9312. Kostelanska, M., Hajslova, J., Zachariasova, M., Malachova, A., Kalachova, K., Poustka, J., et al. (2009). Occurrence of deoxynivalenol and its major conjugate, deoxynivalenol-

biosynthesis of trichothecenes and fumonisins in fusarium. Toxin Reviews, 28, 198–215. Amarasinghe, C. C., Simsek, S., Brûlé-Babel, A., & Fernando, W. G. D. (2016). Analysis of deoxynivalenol and deoxynivalenol-3-glucosides content in Canadian spring wheat cultivars inoculated with Fusarium graminearum. Food Additives & Contaminants: Part A, 33, 1254–1264. Amirahmadi, M., Shoeibi, S., Rastegar, H., Elmi, M., & Mousavi Khaneghah, A. (2017). Simultaneous analysis of mycotoxins in corn flour using LC/MS-MS combined with a modified QuEChERS procedure. Toxin Reviews, 1–9. Bergamini, E., Catellani, D., Dall’asta, C., Galaverna, G., Dossena, A., Marchelli, R., et al. (2010). Fate of Fusarium mycotoxins in the cereal product supply chain: The deoxynivalenol (DON) case within industrial breadmaking technology. Food Additives & Contaminants: Part A, 27, 677–687. Berthiller, F., Crews, C., Dall'Asta, C., Saeger, S. D., Haesaert, G., Karlovsky, P., et al. (2013). Masked mycotoxins: A review. Molecular Nutrition & Food Research, 57, 165–186. Berthiller, F., Dall’asta, C., Corradini, R., Marchelli, R., Sulyok, M., Krska, R., et al. (2009a). Occurrence of deoxynivalenol and its 3-β-Dglucoside in wheat and maize. Food Additives & Contaminants: Part A, 26(4), 507–511. Berthiller, F., Dall’asta, C., Schuhmacher, R., Lemmens, M., Adam, G., & Krska, R. (2005). Masked Mycotoxins: Determination of a deoxynivalenol glucoside in artificially and naturally contaminated wheat by liquid Chromatography−Tandem mass spectrometry. Journal of Agricultural and Food Chemistry, 53, 3421–3425. Berthiller, F., Krska, R., Domig, K. J., Kneifel, W., Juge, N., Schuhmacher, R., et al. (2011). Hydrolytic fate of deoxynivalenol-3-glucoside during digestion. Toxicology Letters, 206(3), 264–267. Berthiller, F., Schuhmacher, R., Adam, G., & Krska, R. (2009b). Formation, determination and significance of masked and other conjugated mycotoxins. Analytical and Bioanalytical Chemistry, 395, 1243–1252. Berthiller, F., Sulyok, M., Krska, R., & Schuhmacher, R. (2007). Chromatographic methods for the simultaneous determination of mycotoxins and their conjugates in cereals. International Journal of Food Microbiology, 119(1), 33–37. Beyer, M., Klix, M. B., Klink, H., & Verreet, J.-A. (2006). Quantifying the effects of previous crop, tillage, cultivar and triazole fungicides on the deoxynivalenol content of wheat grain — a review. Journal of Plant Diseases and Protection, 113, 241–246. Blackwell, B. A., Miller, J. D., & Greenhalgh, R. (1985). 13C NMR study of the biosynthesis of toxins by Fusarium graminearurn. The Journal of Biological Chemistry, 260, 4243–4247. Blandino, M., Haidukowski, M., Pascale, M., Plizzari, L., Scudellari, D., & Reyneri, A. (2012). Integrated strategies for the control of Fusarium head blight and deoxynivalenol contamination in winter wheat. Field Crops Research, 133, 139–149. Boyacioglu, D., Heltiarachchy, N. S., & D’appolonia, B. L. (1993). Additives affect deoxynivalenol (vomitoxin) flour during bread baking. Journal of Food Science, 58, 416–418. Brera, C., Peduto, A., Debegnach, F., Pannunzi, E., Prantera, E., Gregori, E., et al. (2013). Study of the influence of the milling process on the distribution of deoxynivalenol content from the caryopsis to cooked pasta. Food Control, 32, 309–312. Campagnollo, F. B., Ganev, K. C., Khaneghah, A. M., Portela, J. B., Cruz, A. G., Granato, D., ... Sant'Ana, A. S. (2016). The occurrence and effect of unit operations for dairy products processing on the fate of aflatoxin M 1: A review. Food Control, 68, 310–329. Cano-Sancho, G., Sanchis, V., Ramos, A. J., & Marín, S. (2013). Effect of food processing on exposure assessment studies with mycotoxins. Food Additives and Contaminants Part A Chemistry, Analysis, Control, Exposure and Risk Assessment, 30, 867–875. Cheli, F., Pinotti, L., Rossi, L., & Dell'Orto, V. (2013). Effect of milling procedures on mycotoxin distribution in wheat fractions: A review. LWT - Food Science and Technology, 54, 307–314. Cirlini, M., Dall'Asta, C., & Galaverna, G. (2012). Hyphenated chromatographic techniques for structural characterization and determination of masked mycotoxins. Journal of Chromatography A, 1255, 145–152. Cirlini, M., Generotti, S., Dall'Erta, A., Lancioni, P., Ferrazzano, G., Massi, A., et al. (2014). Durum wheat (Triticum durum desf.) lines show different abilities to form masked mycotoxins under greenhouse conditions. Toxins, 6, 81–95. Curic, D., Novotni, D., & Smerdel, B. (2013). Bread making. Engineering aspects of cereal and cereal-based products (pp. 149–174). Boca Raton: CRC Press. Dall'Asta, C., & Berthiller, F. (2015). Masked mycotoxins in food: Formation, occurrence and toxicological relevance. Royal Society of Chemistry. Dall'Asta, C., Falavigna, C., Galaverna, G., & Battilani, P. (2012). Role of maize hybrids and their chemical composition in Fusarium infection and fumonisin production. Journal of Agricultural and Food Chemistry, 60(14), 3800–3808. Dall'Asta, C., Galaverna, G., Aureli, G., Dossena, A., & Marchelli, R. (2008). A LC/MS/MS method for the simultaneous quantification of free and masked fumonisins in maize and maize-based products. World Mycotoxin Journal, 1(3), 237–246. Dall'Asta, C., Galaverna, G., Dossena, A., Sforza, S., & Marchelli, R. (2009). Masked mycotoxins and mycotoxin derivatives in food: The hidden menace. Mycotoxins in food, feed and bioweapons. Berlin Heidelberg: Springer. De Angelis, E., Monaci, L., Pascale, M., & Visconti, A. (2013). Fate of deoxynivalenol, T-2 and HT-2 toxins and their glucoside conjugates from flour to bread: An investigation by high-performance liquid chromatography high-resolution mass spectrometry. Food Additives and Contaminants - Part A, 30, 345–355. De Boevre, M., Di Mavungu, J. D., Maene, P., Audenaert, K., Deforce, D., Haesaert, G., et al. (2012). Development and validation of an LC-MS/MS method for the simultaneous determination of deoxynivalenol, zearalenone, T-2-toxin and some masked metabolites in different cereals and cereal-derived food. Food Additives & Contaminants: Part A, 29(5), 819–835. De Boevre, M., Jacxsens, L., Lachat, C., Eeckhout, M., Di Mavungu, J. D., Audenaert, K., et al. (2013). Human exposure to mycotoxins and their masked forms through cereal-

22

Trends in Food Science & Technology 71 (2018) 13–24

A.M. Khaneghah et al.

Pitt, J. I., & Hocking, A. D. (2009). Fungi and food spoilage (3a Ed.). New York: Springer. Pitt, J. I., Taniwaki, M. H., & Cole, M. B. (2013). Mycotoxin production in major crops as influenced by growing, harvesting, storage and processing, with emphasis on the achievement of food safety objectives. Food Control, 32, 205–215. Plasencia, J., & Mirocha, C. J. (1991). Isolation and characterization of zearalenone sulfate produced by Fusarium spp. Applied And Environmental Microbiology, 57, 146–150. Pleadin, J., Vahčić, N., Perši, N., Ševelj, D., Markov, K., & Frece, J. (2013). Fusarium mycotoxins' occurrence in cereals harvested from Croatian fields. Food Control, 32(1), 49–54. Posner, E. S., & Hibbs, A. N. (1999). Wheat flour milling (2 ed.). St. Paul: AACC 341 pp. Quarta, A., Mita, G., Haidukowski, M., Logrieco, A., Mulè, G., & Visconti, A. (2006). Multiplex PCR assay for the identification of nivalenol, 3-and 15-acetyl-deoxynivalenol chemotypes in Fusarium. FEMS Microbiology Letters, 259, 7–13. Rasmussen, P. H., Nielsen, K. F., Ghorbani, F., Spliid, N. H., Nielsen, G. C., & Joørgensen, L. N. (2012). Occurrence of different trichothecenes and deoxynivalenol- 3-β-D-glucoside in naturally and artificially contaminated Danish cereal grains and whole maize plants. Mycotoxin Research, 28, 181–190. Rychlik, M., Humpf, H., Marko, D., Dänicke, S., Mally, A., Berthiller, F., et al. (2014). Proposal of a comprehensive definition of modified and other forms of mycotoxins including “masked” mycotoxins. Mycotoxin Research, 30, 197–205. Samar, M. M., Neira, M. S., Resnik, S. L., & Pacin, A. (2001). Effect of fermentation on naturally occurring deoxynivalenol (DON) in Argentinean bread processing technology. Food Additives and Contaminants, 18, 1004–1010. Sanchis, V., & Magan, N. (2004). Environmental conditions affecting mycotoxins. In N. Magan, & M. Olsen (Eds.). Mycotoxins in food: Detection and control (pp. 174–189). Cambridge (UK): Woodhead Publishing. dos Santos, J. S., Souza, T. M., Ono, E. Y. S., Hashimoto, E. H., Bassoi, M. C., de Miranda, M. Z., et al. (2013). Natural occurrence of deoxynivalenol in wheat from Paraná State, Brazil and estimated daily intake by wheat products. Food Chemistry, 138(1), 90–95. Scherm, B., Balmas, V., Spanu, F., Pani, G., Delogu, G., Pasquali, M., et al. (2013). Fusarium culmorum: Causal agent of foot and root rot and head blight on wheat. Molecular Plant Pathology, 14, 323–341. Scheuer, P. M., de Francisco, A., de Miranda, M. Z., & Limberger, V. M. (2011). Trigo: Características e Utilização na Panificação. Revista Brasileira de Produtos Agroindustriais, 13, 211–222. Schisler, D. A., Khan, N. I., & Boehm, M. J. (2002). Biological control of Fusarium head blight of wheat and deoxynivalenol levels in grain via use of microbial antagonists. Advances in Experimental Medicine and Biology, 504, 53–70. Schmeitzl, C., Warth, B., Fruhmann, P., Michlmayr, H., Malachová, A., Berthiller, F., et al. (2015). The metabolic fate of deoxynivalenol and its acetylated derivatives in a wheat suspension culture: Identification and detection of DON-15-O-glucoside, 15acetyl-DON-3-O-glucoside and 15-acetyl-DON-3-sulfate. Toxins, 7, 3112–3126. Schollenberger, M., Drochner, W., Rüfle, M., Suchy, S., Terry-Jara, H., & Müller, H. M. (2005). Trichothecene toxins in different groups of conventional and organic bread of the German market. Journal of Food Composition and Analysis, 18(1), 69–78. Schothorst, R. C., & Jekel, A. A. (2001). Determination of trichothecenes in wheat by capillary gas chromatography with flame ionisation detection. Food Chemistry, 73(1), 111–117. Scudamore, K. A., Hazel, C. M., Patel, S., & Scriven, F. (2009). Deoxynivalenol and other Fusarium mycotoxins in bread, cake, and biscuits produced from UK-grown wheat under commercial and pilot scale conditions. Food Additives & Contaminants: Part A, 26, 1191–1198. Škrbić, B., Malachova, A., Živančev, J., Veprikova, Z., & Hajšlová, J. (2011). Fusarium mycotoxins in wheat samples harvested in Serbia: A preliminary survey. Food Control, 22(8), 1261–1267. Šliková, S., Gavurníková, S., Šudyová, V., & Gregová, E. (2013). Occurrence of deoxynivalenol in wheat in Slovakia during 2010 and 2011. Toxins, 5(8), 1353–1361. http://doi.org/10.3390/toxins5081353. Sobrova, P., Adam, V., Vasatkova, A., Beklova, M., Zeman, L., & Kizek, R. (2010). Deoxynivalenol and its toxicity. Interdisciplinary Toxicology, 3, 94–99. Sudakin, D. L. (2003). Trichothecenes in the environment: Relevance to human health. Toxicology Letters, 143, 97–107. Suman, M., Bergamini, E., Castellani, D., & Manzitti, A. (2013). Development and validation of a liquid chromatography/linear ion trap mass spectrometry method for the quantitative determination of deoxynivalenol-3-glucoside in processed cereal-derived products. Food Chemistry, 136, 1–15. Turner, P. C., Burley, V. J., Rothwell, J. A., White, K. L. M., Cade, J. E., & Wild, C. P. (2008a). Dietary wheat reduction decreases the level of urinary deoxynivalenol in UK adults. Journal of Exposure Science and Environmental Epidemiology, 18, 392–399. Turner, P. C., Rothwell, J. A., White, K. L. M., Gong, Y., Cade, J. E., & Wild, C. P. (2008b). Urinary deoxynivalenol is correlated with cereal intake in individuals from the United Kingdom. Environmental Health Perspectives, 116, 21–25. Valle-Algarra, F. M., Mateo, E. M., Medina, A., Mateo, F., Gimeno-Adelantado, J. V., & Jiménez, M. (2009). Changes in ochratoxin A and type B trichothecenes contained in wheat flour during dough fermentation and bread-baking. Food Additives and Contaminants, 26(6), 896–906. Varga, E., Wiesenberger, G., Hametner, C., Ward, T. J., Dong, Y., Schöfbeck, D., et al. (2015). New tricks of an old enemy: Isolates of Fusarium graminearum produce a type A trichothecene mycotoxin. Environmental Microbiology, 17(8), 2588–2600. Vidal, A., Marín, S., Ramos, A. J., Cano-Sancho, G., & Sanchis, V. (2013). Determination of aflatoxins, deoxynivalenol, ochratoxin A and zearalenone in wheat and oat based bran supplements sold in the Spanish market. Food and Chemical Toxicology, 53, 133–138. http://doi.org/10.1016/j.fct.2012.11.020. Vidal, A., Sanchis, V., Ramos, A. J., & Marín, S. (2016). The fate of deoxynivalenol

3-glucoside, in beer and some brewing intermediates. Journal of Agricultural and Food Chemistry, 57, 3187–3194. Lancova, K., Hajslova, J., Kostelanska, M., Kohoutkova, J., Nedelnik, J., Moravcova, H., et al. (2008). Fate of trichothecene mycotoxins during the processing: Milling and baking. Food Additives & Contaminants: Part A, 25, 650–659. Li, F., Jiang, D., Zhou, J., Chen, J., Li, W., & Zheng, F. (2016). Mycotoxins in wheat flour and intake assessment in Shandong province of China. Food Additives & Contaminants: Part B, 9(3), 170–175. Liang, J. M., Xayamongkhon, H., Broz, K., Dong, Y., McCormick, S. P., Abramova, S., et al. (2014). Temporal dynamics and population genetic structure of Fusarium graminearum in the upper Midwestern United States. Fungal Genetics and Biology, 73, 83–92. Malachova, A., Dzuman, Z., Veprikova, Z., Vaclavikova, M., Zachariasova, M., & Hajslova, J. (2011). Deoxynivalenol, deoxynivalenol-3-glucoside, and enniatins: The major mycotoxins found in cereal-based products on the czech market. Journal of Agricultural and Food Chemistry, 59, 12990–12997. Malbrán, I., Mourelos, C. A., Girotti, J. R., Balatti, P. A., & Lori, G. A. (2014). Toxigenic capacity and trichothecene production by Fusarium graminearum isolates from Argentina and their relationship with aggressiveness and fungal expansion in the wheat spike. Phytopathology, 104, 357–364. Merhej, J., Boutigny, A. L., Pinson-Gadais, L., Richard-Forget, F., & Barreau, C. (2010). Acidic pH as a determinant of TRI gene expression and trichothecene B biosynthesis in Fusarium graminearum. Food Additives & Contaminants: Part A, 27, 710–717. Merhej, J., Richard-Forget, F., & Barreau, C. (2011). Regulation of trichothecene biosynthesis in Fusarium: Recent advances and new insights. Applied Microbiology and Biotechnology, 91, 519–528. Milani, J., & Maleki, G. (2014). Effects of processing on mycotoxin stability in cereals. Journal of the Science of Food and Agriculture, 94(12), 2372–2375. Miller, J. D. (1995). Fungi and mycotoxins in grain: Implications for stored product research. Journal of Stored Products Research, 31, 1–16. Morgavi, D. P., & Riley, R. T. (2007). An historical overview of field disease outbreaks known or suspected to be caused by consumption of feeds contaminated with Fusarium toxins. Animal Feed Science and Technology, 137, 201–212. Müller, H. M., & Schwadorf, K. (1993). A survey of the natural occurrence of Fusarium toxins in wheat grown in a southwestern area of Germany. Mycopathologia, 121(2), 115–121. Nakagawa, H., He, X., Matsuo, Y., Singh, P. K., & Kushiro, M. (2017). Analysis of the masked metabolite of deoxynivalenol and Fusarium resistance in CIMMYT wheat germplasm. Toxins, 9, 238. Nakagawa, H., Ohmichi, K., Sakamoto, S., Sago, Y., Kushiro, M., Nagashima, H., ... Nakajima, T. (2011). Detection of a new Fusarium masked mycotoxin in wheat grain by high-resolution LC–Orbitrap™ MS. Food Additives & Contaminants: Part A, 28, 1447–1456. National Toxicology Program (2009). Chemical information review document for deoxynivalenol [CAS No. 51481-10-8]. National Institute of Environmental Health Sciences. National Institutes of Health. U.S Department of Health and Human Services. Available at: https://ntp.niehs.nih.gov/ntp/noms/support_docs/ deoxynivalenol060809.pdf Accessed 03 September 2017 . Numanoglu, E., Uygun, U., Koksel, H., & Solfrizzo, M. (2010). Stability of Fusarium toxins during traditional Turkish maize bread production. Quality Assurance and Safety of Crops & Foods, 2, 84–92. Ok, H. E., Chang, H. J., Choi, S. W., Cho, T. Y., Oh, K. S., & Chun, H. S. (2009). Occurrence and intake of deoxynivalenol in cereal-based products marketed in Korea during 2007-2008. Food Additives and Contaminants: Part B Surveillance, 2(2), 154–161. http://doi.org/10.1080/19440040903367179. Ok, H. E., Choi, S. W., Chang, H. J., Chung, M. S., & Chun, H. S. (2011). Occurrence of five 8-ketotrichothecene mycotoxins in organically and conventionally produced cereals collected in Korea. Food Control, 22, 1647–1652. Ostry, V., Malir, F., Toman, J., & Grosse, Y. (2017). Mycotoxins as human carcinogens—the IARC Monographs classification. Mycotoxin Research, 33, 65–73. Ovando-Martínez, M., Ozsisli, B., Anderson, J., Whitney, K., Ohm, J. B., & Simsek, S. (2013). Analysis of deoxynivalenol and deoxynivalenol-3-glucoside in hard red spring wheat inoculated with Fusarium graminearum. Toxins, 5(12), 2522–2532. Pacin, A. M., Resnik, S. L., & Martinez, E. J. (2011). Concentrations and exposure estimates of deoxynivalenol in wheat products from Argentina. Food Additives and Contaminants: Part B Surveillance, 4(2), 125–131. Palacios, S. A., Erazo, J. G., Ciasca, B., Lattanzio, V. M. T., Reynoso, M. M., Farnochi, M. C., et al. (2017). Occurrence of deoxynivalenol and deoxynivalenol-3-glucoside in durum wheat from Argentina. Food Chemistry, 230, 728–734. Palazzini, J. M., Ramirez, M. L., Torres, A. M., & Chulze, S. N. (2007). Potential biocontrol agents for Fusarium head blight and deoxynivalenol production in wheat. Crop Protection, 26(11), 1702–1710. Panthi, A. (2012). Characterization of chemotype and aggressiveness of Nebraska isolates of Fusarium graminearum. Theses, dissertations, & student Scholarship: Agricultural leadershipLincoln, Nebraska: Education & Communication Department. University of Nebraska-Lincoln. Paper 93 http://digitalcommons.unl.edu/aglecdiss/93. Panthi, A., Hallen-Adams, H., Wegulo, S. N., Hernandez Nopsa, J., & Baenziger, P. S. (2014). Chemotype and aggressiveness of isolates of Fusarium graminearum causing head blight of wheat in Nebraska. Canadian journal of Plant Pathology, 36, 447–455. Pasquali, M., & Migheli, Q. (2014). Genetic approaches to chemotype determination in type B-trichothecene producing fusaria. International Journal of Food Microbiology, 189, 164–182. Pereira, V. L., Fernandes, J. O., & Cunha, S. C. (2014). Mycotoxins in cereals and related foodstuffs: A review on occurrence and recent methods of analysis. Trends in Food Science & Technology, 36(2), 96–136. Pestka, J. J. (2007). Deoxynivalenol: Toxicity, mechanisms and animal health risks. Animal Feed Science and Technology, 137, 283–298.

23

Trends in Food Science & Technology 71 (2018) 13–24

A.M. Khaneghah et al.

Wegulo, S. N. (2012). Factors influencing deoxynivalenol accumulation in small grain cereals. Toxins, 4(11), 1157–1180. WHO (World Health Organization) (2001). Deoxynivalenol. Food additives series 47, Safety evaluation of certain mycotoxins in food 419e528. Yang, C.-H. (2006). Fermentation. In Y. H. Hui, H. Corke, I. D. Leyn, W.-K. Nip, & N. Cross (Eds.). Bakery products science and technology (pp. 261–271). Ames: Blackwell Publishing. Young, J. C., Fulcher, R. G., Hayhoe, J. H., Scott, P. M., & Dexter, J. E. (1984). Effect of milling and baking on deoxynivalenol (vomitoxin) content of eastern Canadian wheat. Journal of Agricultural and Food Chemistry, 32, 659–664. Yuen, G. Y., & Schoneweis, S. D. (2007). Strategies for managing Fusarium head blight and deoxynivalenol accumulation in wheat. International Journal of Food Microbiology, 119(1), 126–130. Zachariasova, M., Vaclavikova, M., Lacina, O., Vaclavik, L., & Hajslova, J. (2012). Deoxynivalenol oligoglycosides: New “masked” Fusarium toxins occurring in malt, beer, and breadstuff. Journal of Agricultural and Food Chemistry, 60(36), 9280–9291. Zhang, H., & Wang, B. (2014). Fate of deoxynivalenol and deoxynivalenol-3-glucoside during wheat milling and Chinese steamed bread processing. Food Control, 44, 86–91.

through wheat processing to food products. Current Opinion in Food Science, 11, 34–39. Visconti, A., Haidukowski, E. M., Pascale, M., & Silvestri, M. (2004). Reduction of deoxynivalenol during durum wheat processing and spaghetti cooking. Toxicology Letters, 153, 181–189. Wang, L., Shao, H., Luo, X., Wang, R., Li, Y., Li, Y., et al. (2016). Effect of ozone treatment on deoxynivalenol and wheat quality. PloS One, 11, e0147613. Ward, T. J., Bielawski, J. P., Kistler, H. C., Sullivan, E., & O'Donnell, K. (2002). Ancestral polymorphism and adaptive evolution in the trichothecene mycotoxin gene cluster of phytopathogenic Fusarium. Proceedings of the National Academy of Sciences, 99, 9278–9283. Warth, B., Fruhmann, P., Wiesenberger, G., Kluger, B., Sarkanj, B., Lemmens, M., et al. (2015). Deoxynivalenol-sulfates: Identification and quantification of novel conjugated (masked) mycotoxins in wheat. Analytical and Bioanalytical Chemistry, 407, 1033–1039. Webb, C., & Owens, G. W. (2003). Milling and flour quality. In S. P. Cauvain (Ed.). Woodhead publishing series in food science, technology and nutrition (pp. 200–219). Woodhead Publishing (Bread Making).

24