Journal Pre-proof

Mycotoxin contamination and control strategy in human, domestic animal and poultry:
A review

Md Atiqul Haque, Yihui Wang, Zhiqiang Shen, Xiaohui Li, Muhammad Kashif
Saleemi, Cheng He

PII: S0882-4010(19)32135-7
DOI: https://doi.org/10.1016/j.micpath.2020.104095
Reference: YMPAT 104095

To appear in: Microbial Pathogenesis

Received Date: 10 December 2019

Revised Date: 17 February 2020
Accepted Date: 21 February 2020

Please cite this article as: Haque MA, Wang Y, Shen Z, Li X, Saleemi MK, He C, Mycotoxin
contamination and control strategy in human, domestic animal and poultry: A review, Microbial
Pathogenesis (2020), doi: https://doi.org/10.1016/j.micpath.2020.104095.

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 1 Mycotoxin Contamination and Control Strategy in Human, Domestic
2 Animal and Poultry: A Review
3
4 Md Atiqul Haque1,2, Yihui Wang1, Zhiqiang Shen3, Xiaohui Li1, Muhammad Kashif Saleemi4, Cheng He1*

5 1
Key Lab of Animal Epidemiology and Zoonoses of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural
6 University, Beijing, 100193, China
7 2
Department of Microbiology, Faculty of Veterinary & Animal Science, Hajee Mohammad Danesh Science and Technology University,
8 Dinajpur-5200, Bangladesh
9 3
Binzhou Animal Science and Veterinary Medicine Academy of Shandong Province, Binzhou 256600, China
10 4
Faculty of Veterinary Science, University of Agriculture, Faisalabad, 38040, Pakistan
11 ∗ Corresponding author
12 Mailing address: Key Lab of Animal Epidemiology and Zoonoses of Ministry of Agriculture, College of Veterinary Medicine, China
13 Agricultural University, Beijing, 100193, China. E-mail address: [email protected]
14
15 Abstract
16
17 Mycotoxins are secondary metabolites produced mainly by fungi belonging to the genera
18 Aspergillus, Fusarium, Penicillium, Claviceps, and Alternaria that contaminate basic food
19 products throughout the world, whether developing countries becoming predominantly
20 affected. Currently, more than 500 mycotoxins are reported in which the most important
21 concern to public health and agriculture include AFB1, OTA, TCTs (especially DON, T-2,
22 HT-2), FB1, ZEN, PAT, CT, and EAs. The presence of mycotoxin in significant quantities
23 poses health risks varying from allergic reactions to death on both humans and animals. This
24 review brings attention to the present status of mycotoxin contamination of food products and
25 recommended control strategies for mycotoxin mitigation. Humans are exposed to
26 mycotoxins directly through the consumption of contaminated foods while, indirectly through
27 carryover of toxins and their metabolites into animal tissues, milk, meat and eggs after
28 ingestion of contaminated feeds. Pre-harvest (field) control of mycotoxin production and
29 post-harvest (storage) mitigation of contamination represent the most effective approach to
30 limit mycotoxins in food and feed. Compared with chemical and physical approaches,
31 biological detoxification methods regarding biotransformation of mycotoxins into less toxic
32 metabolites, are generally more unique, productive and eco-friendly. Along with the
33 biological detoxification method, genetic improvement and application of nanotechnology
34 show tremendous potential in reducing mycotoxin production thereby improving food safety
35 and food quality for extended shelf life. This review will primarily describe the latest
36 developments in the formation and detoxification of the most important mycotoxins by
37 biological degradation and other alternative approaches, thereby reducing the potential
38 adverse effects of mycotoxins.

39 Keywords: Mycotoxin; biological detoxification; toxigenic fungus; nanotechnology.

40 1. Introduction

41 Mycotoxins are naturally occurring toxins produced by certain species of Aspergillus,

42 Fusarium, Penicillium, Claviceps, and Alternaria. Recently about 100,00 fungi have been
43 identified, among these more than 500 mycotoxins have been reported as potentially
44 toxigenic, major mycotoxins influencing human and animal health include aflatoxins (AFTs),
45 ochratoxins (OTs), trichothecenes (TCTs), fumonisins (FUMs), zearalenone (ZEN), patulin
46 (PAT), citrinin (CT) and ergot alkaloids (EAs) [1,2,3]. These compounds produced by mould
47 infection at pre- and post-harvest crops under natural conditions worldwide. The historical
48 evidence of the mycotoxicological risk has existed since the first stage of organized
49 agricultural production. The first report on human mycotoxicoses dates back to Middle Ages,
50 “St. Anthony’s Fire” which was associated with toxicity of both gangrenous and convulsive
51 form due to ergotism from Claviceps purpura related to moldy rye [4]. The mycotoxicity
52 may induce acute to chronic effects resulting in carcinogenic, mutagenic, teratogenic,
53 immunosuppressive and endocrine-disrupting effects both on humans and animals [5]. The
54 acute toxicity may result in consuming a moderate amount of toxin causing deterioration of
55 liver or kidney functions extremely leading to death. Chronic toxicity may result in
56 consuming moderate to low quantity of toxins causing production loss in the form of slow
57 growth rate, reduced productivity and inferior market quality. Consumption of low quantity
58 of toxins often susceptible to various infectious diseases specially secondary bacterial
59 infections or a heavy progression of some often encountered parasitic diseases [6]. The
60 predisposing conditions for toxin production are mainly related to biological, chemical,
61 physical or environmental (Fig. 1). It is estimated that approximately 25-50% of cereal
62 products produced world-wide are significantly contaminated with mycotoxins to a varying
63 degree and 5-10% of which are irreversible causing huge economic losses [7]. Mycotoxins
64 cause mortality of human and animal, or increased health and veterinary care cost, or
65 decreased production efficiency, or by rendering commodities unacceptable for national or
66 international trade [8]. Regulatory guidelines and limits for mycotoxins have been set by the
67 European Union (EU), Food and Drug Administration (FDA) of the USA and other countries
68 for both import and export of affected commodities. In this review, we discussed the recent
69 evidence on mycotoxicity associated risks to human and livestock health, prevention and
70 control strategies to ensure consumer's health and safety.

71
 72

73

74

75

76

77

78
79
80
81
82
83
84
85
86
87 Fig. 1. Factors affecting mycotoxin occurrence in the food and feed chain [9,10]
88

89 2. Occurrence and types of mycotoxins

90 Mycotoxins are small and quite stable toxic molecules, extremely difficult to remove or
91 eradicate present in agricultural and animal products. The origin, available food, affected
92 species, pathological effects, and toxicities are summarized in Table 1 and tolerable limits of
93 different mycotoxins in the food chain by different countries and authorities are shown in
94 Table 2. Mycotoxin contamination usually exists in the field by foods and feeds following
95 infection of toxogenic fungus in the pre-harvest period, then suitable environmental
96 conditions for spoilage fungi during processing, storage and distribution of harvested
97 products in post-harvest period. Mycotoxin can enter to human food chain directly by
98 consuming contaminated plants and food products and indirectly through residues in milk,
99 meat, eggs, and their derivates. The mycotoxin occurrence in the food chain and their residual
100 effect on human and animal health has been shown in Fig. 2.
101

102 Fig. 2. Mycotoxins occurrence in the food chain and their residual effect on human and animal [11-14]

103 2.1 Aflatoxins (AFTs)

104 AFTs are difuranocoumarins or furanocoumarins mainly produced by Aspergillus spp.( flavus
105 and parasiticus) [15,16, 17]. There are >20 types of AFT molecules, the most prominent are
106 difurocoumarocyclopentenone group (AFB1, AFB2, AFM1, and AFM2) and
107 difurocoumarolactone group (AFG1 and AFG2) [18]. AFB1, AFB2, AFG1, and AFG2 are
108 ubiquitous in food and feedstuff while, AFM1 derived from AFB1 in the liver by hepatic
109 microsomal cytochrome P450, can enter through blood circulation and be excreted into milk
110 [19,20]. The toxicity profile of AFTs is B1>M1>G1>B2>M2/G2 etc. Among all discovered
111 mycotoxins, AFTs are the most potent with acute toxicological and chronic
112 hepatocarcinogenic effects in the liver based on their reactivity with DNA, RNA, enzymes,
113 and proteins [21]. Cumulative evidence link chronic aflatoxicosis with hepatocellular
114 carcinoma (HCC) or liver cancer while acute aflatoxicosis with abdominal pain, vomiting,
115 edema, and death have been reported in China, India, Malaysia and Kenya [22,23]. Recent
116 research revealed that the global burden of AFT may contribute to the occurrence of 4.6-28.2%
117 of all global HCC, the third leading cause of cancer deaths globally and is also susceptible to
118 lung, GI tracts and cause kidney injury in mice and calf models [19, 24]. In poultry, ducks are
119 the most sensitive to AFTs followed by turkey, quails, broiler, and layers; toxicity includes
120 fatty liver, kidney disorder, leg, and bone deformity, reduced weight gain and productivity,
121 immunosuppression, small and poor quality eggs, pigmentation problems, etc. [25, 26]. In an
122 experimental study it is found that AFB1 caused severe kidney and liver damage in broiler
123 birds along with concurrent infection with Fowl Adenovirus-4 [27].

124 Table 1: Major food borne mycotoxins, their main producing fungal species, the commodities most
125 frequently contaminated, and their primary health effects on animals and humans
Mycotoxin Fungal species Food commodity Affected species Pathological effects and Ref.
toxicities
Maize, wheat, rice, Birds: Duck, turkey,
Aspergillums ( flavus, nomius, spices, sorghum, poult, pheasant,
Aflatoxins parasiticus, arachidicola, ground nuts, tree chicken, quail Carcinogic, mutagenic, 20,
(AFB1, AFB2, bombycis, pseudotamarii, nuts, almonds, Mammals: pigs, dog, hepatoxic, 28-32,
AFG1, AFG2, minisclerotigenes, rambellii) oilseeds, dried fruits, cattle, sheep, cat, teratogenic, nephrotoxic, 34
AFM1, AFM2) Emericella (astellata, cheese, spices, milk & monkey, human immunosuppressive
venezuelensis, olivicola) dairy products, eggs, Fish: Laboratory
meat animal

Aspergillus (alutaceus, alliaceus, nephrotoxic, hepatotoxic,

niger, auricomus, glaucus, steynii, Cereals, barley, neurotoxic, mutagenic,
Ochratoxins citricus, fonsecaeus, ochraceus, wheat, dried vine Swine, dog, duck, teratogenic, 20,
(OTA, OTB, carbonarius, cretensis, meleus) fruit, wine, coffee, chicken, rat, human immunodepressants, 28-33
OTC) Neopetromyces muricatus, oats, spices, rye, carcinogenic (urinary tract
Penicillium (viridicatum, raisins, grape juice tumors), inhibition of protein
verrucosum, cyclopium, synthesis
carbonarius, verrucosum)
Fusarium (sporotrichioides, cytotoxicity, immuno-
graminearum, cerealis, depressants, mutagenic,
Trichothecenes moniliforme, myrothecium, Swine, cattle, neurotoxic, anorexia & 20,28,
(T-2, HT-2, lunulosporum, culmorum, equiseti, Cereals, cereal chicken, diarrhea, weight loss, 29,31-33
DAS, NIV, poae) Cephalosporium sp., products turkey, horse, rat, neuroendocrine changes,
DON) Myrothecium sp., Trichoderma sp., dog, leukocytosis, hemorrhaging, or
Verticimonosporium sp. mouse, cat, human circulatory shock, oral lesions,
Phomopsis sp., Stachybotrys sp. dermatitis, infertility

Fusarium (anthophilum, 20,28,29,

Fumonisins moniliforme, dlamini, globosum, Maize, maize Horses, swine, rats, hepatotoxic, immunotoxic, 31-33
(FB1, FB2, napiforme, proliferatum, nygamai, products, corn based chicken cytotoxicity, carcinogenic,
FB3) verticillioides, oxysporum), products, sorghum, human apoptosis, pulmonary edema,
Alternaria alternate asparagus, rice, milk immune-depressants

Fusarium( graminearum, Barley, oats, wheat Swine, dairy cattle, carcinogenicity,

Zearalenone culmorum, crookwellense, rice, sorghum, chicken, turkey, lamb, immunotoxicity, genotoxicity, 20,28,29,
(ZEN) equiseti, sporotrichioides, sesame, soybeans, rat, mouse, guinea reproductive & developmental 31,32
cerealis, incarnatum) cereal-based products pig, human toxicity, oestogenic effects,
prolapse of vagina, abortion
Birds: Chicken,
Aspergillums( clavatus, ongivesica, Apples, apple juice, chicken embryo, quail neurotoxicity, embryotoxicity,
Patulin terreus), Penicillium (expansum, cherries, cereals, Mammals: Cat, cattle, teratogenicity, immunotoxicity, 28,
(PAT) patulum, crustosum, griseofulvum) apricots, grapes, mouse, rabbit, rat, convulsions, dyspnea, 30-32
Byssochlamys sp. pears, peaches, olives, human pulmonary congestion, edema,
bilberries Others: Brine shrimp, ulceration of GI tract
guppie, zebra
stored grains and
Citrinin Penicillium citrinum, P. expansum, grain-based products, reproductive toxicity,
(CT) P. radicicola, P. verrucosum cheese, sake, and red Poultry, pig, human nephrotoxic, embryotoxic, 28,32,34
Monascus purpureus, M. ruber pigments as well as in teratogenic, hepatotoxic,
spices immunotoxic, carcinogenic
Neurotoxicity,
Ergot alkaloids endocrine disruption
(Ergometrine, Claviceps (africanana, purpurea, Wheat, rye, hay, Fish larvae, pigs, gangrenous form: edema of the
ergotamine, fusiformis, paspali) barley, millet, oats, cattle, legs, paraesthesias, gangrene at 28
ergosine, Neotyphodium coenophialum sorghum, triticale, swine, horses, swine, the tendons
ergocristine, grass human convulsive form: nausea,
ergocryptine & vomiting,
ergocornine ) drowsiness, ataxia,
convulsions, blindness,
paralysis
126 2.2 Trichothecenes (TCTs)

127 TCTs consist of approximately 200 structurally related compounds, divided into 4 types (A-
128 D), importantly type-B: deoxynivalenol (DON) and nivalenol (NIV) and type-A: T-2 toxin
129 and its major metabolite HT-2 toxin [35,36]. The most acutely toxic TCT in animals is T-2
130 while sensitivity varies among animal species; in dairy cows, it has been related to feed
131 refusal, gastroenteritis, intestinal hemorrhages, and death while in poultry it causes intestinal
132 lesion and weight loss [37,38]. In research reports it is found that DON concentrations @ 1-7
133 mg/kg diet significantly decreasing absorption area of villus surface and also altering the
134 permeability of the gastrointestinal tract resulting both immunosuppressive and
135 immunomodulating effects in poultry [39,40,41]. DON toxicity has been associated with
136 animal and human gastroenteritis outbreak resulting in typical acute symptoms including
137 nausea, vomiting, abdominal pain, diarrhea, headache, dizziness, or fever thereby also called
138 it vomitoxin [Vidal 2018]. Several outbreaks of acute DON toxicity in humans have been
139 reported in India, China, and the USA to strengthen the potential risk for humans [22].

140 2.3 Fumonisins (FUMs)

141 There are 28 known important FUM analogs among which FB1 is the most prominent
142 followed by FB2 and FB3 [36]. Consumption of corn-based feed containing FUMs are
143 known to be responsible of a fatal brain disease, equine leuko-encephalomalacia in horse and
144 swelling of lungs and thorax, porcine pulmonary edema syndrome in pig [15]. The mode of
145 action by which FUM causes toxicity in animals seems to be due to the collapse of
146 sphingolipid metabolism [40]. The occurrence of FB1 is correlated with the presence of a
147 higher incidence of esophageal cancer is related to the intake of corn grains containing FUMs
148 in human have been reported in South Africa and China [36,43]. In other studies reported that
149 esophageal cancer and neural tube defect has been linked to consumption of FB1
150 contaminated maize in human as well as numerous illness in animal have been observed
151 along the US-Mexico border, in Guatemala, Egypt, South Africa and China [36,44,45].

152 2.4 Ochratoxins (OTs)

153 OTs were discovered as three secondary metabolite forms, A, B and C differ in that OTB is
154 nonchlorinated and OTC is an ethyl ester form of OTA [15,46,47]. OTA is found in
155 beverages (beer and wine) contaminated with Aspergillus ochraceus and certain wines
156 specially made from vine fruits such as grapes contaminated with Aspergillus carbonariua
157 [48,49]. OTA is a nephrotoxin as well as a hepatotoxin, immune suppressant, potent teratogen
158 and carcinogen to all animal species. OTA toxicity in poultry causes weakness, anemia,
159 reduced feed consumption, decreased productivity, poor feathering, excessive mortality at
160 high dietary concentration and hypocarotenidemia in broilers [40]. In human studies, OTA
161 has been linked with fatal renal disease, such as Balkan endemic nephropathy, a progressive
162 chronic nephritis and upper urothelial tract cancer [22, 35]. It also causes porcine nephropathy
163 (kidney damage) in pig and tail necrosis in newborn piglets [46].

164

Table 2: Maximum tolerable limit (MTL) and maximum residue limit (MRL) of mycotoxin in the food chain [ 50-56]
Country / authority Mycotoxins Food commodities Limit (µg/kg)
MTL MRL
USA Total AFT Meat 20 20
Egg 20 20
AFM1 Milk, milk products 0.5 -
ZEN - 30 ng/kg BW TDI -
Meat 4 4
Total AFT Egg 4 4
Milk 4 -
AFB1 Milk 2 -
AFM1 Milk 0.05 -
Infant milk 0.025 -
EU Pork ≤25 -
OTA Milk 5 ng/kg BW TDI -
- 120 ng/kg BW TWI -
DON - 1 µg/kg BW/TDI -
FB1, FB2, FB3 - 2 µg/kg BW/PMTDI -
ZEN - 60 to 200 -
PAT - 0.4 µg/kg BW/PMTDI -
WHO AFM1 Milk 0.50 -
FB1 - 2 µg/kg/BW PMTDI -
ZEN - 0.5 µg/kg BW MTDI -
Joint FAO/WHO OTA - 100 ng/kg PTWI -
FUM - 2 µg/kg/BW PMTDI -
DON - 1 µg/kg/BW PMTDI
Canada ZEN - 20 ng/kg BW TDI -
Norway ZEN - 20 ng/kg BW TDI -
Italy OTA Pork meat and derived products 1 -
Estonia OTA Pig liver 10
Pork - 25
OTA Pig kidneys 10 10
Denmark
Pig liver - 25
ZEN - 20 ng/kg BW TDI -
Infant milk (<3 years0 0.03 -
AFM1 Milk powder 0.5 -
France Infant milk powder (>3 years) 0.3 -
FB1 Avian kidney and liver - 100
China AFM1 Milk and milk products 0.5 -
Total AFT Meat 10 -
Japan Egg 10 -
AFM1 Milk 0.5 -
Korea AFM1 Milk 0.5 -
Malaysia AFM1 Milk 0.5 -
Infant milk 0.025 -
TDI= tolerable daily intake; TWI =tolerable weekly intake; PMTDI= provisional maximum tolerable daily intake; BW =bodyweight

165
166
167
168 2.5 Zearalenone (ZEN)

169 ZEN is known as mycoestrogen, a subset of naturally occurring estrogenic compounds which
170 is heat-stable and capable of binding estrogen receptors, causing adverse impact involved
171 with reproductive disorders and hyperestrogenism, both in humans and farm animals [46,57].
172 Swine are reported as the most sensitive domestic animals affected on the farm compared to
173 cattle and sheep, while it causes estrogenic syndrome including enlarged mammary gland and
174 genitalia, atrophy of ovaries and testes, abortion and stillbirths, reduced litter size and piglets
175 viability [36,46]. Occurrences of swine estrogenic syndrome have frequently evident in North
176 America and Europe but also high levels of ZEN have been reported from China and other
177 Asian countries [36]. In laboratory animals (mice, rats, guinea pig, hamster, and rabbit) it
178 causes reproductive toxicity and premature puberty syndrome in humans [38,42].

179 2.6 Citrinin (CIT)

180 CIT is a secondary toxic benzopyran metabolite generally formed post-harvest condition and
181 mainly found in stored grains, but also present in plant origin products such as rice, wheat,
182 barley, rye, beans, pomaceous fruits, fruit juices, nuts and spices, and also in spoiled dairy
183 products [34,58]. It represents a significant health hazard especially in tropical countries
184 where it is a major source of food poisoning after fungal contamination. CIT is associated
185 with yellowed rice disease in Japan and acts as a nephrotoxin in all animal species but acute
186 toxicity differs in various species [46,49]. CIT is quickly absorbed and disseminated in the
187 liver and kidney, the human toxicokinetic study showed that 40% of CIT was excreted via
188 urine [42]. In a study report, it is found that it has been related to pig nephropathy after the
189 consumption of contaminated barley grains [59]. It can also act concurrently with OTA to
190 depress the mechanism of RNA synthesis in murine kidneys [15,46].

191 2.7 Patulin (PAT)

192 PAT considered a serious hazard for fruits at the post-harvest stage, first contacts the surface,
193 then contaminates whole fruit and can spread to other fruits stored together cause the disease
194 known as "blue mold" which is common in apple, cherry, figs and other fruits [46]. Apples
195 are found to be an vital source of PAT since they are readily infected by Penicillium
196 expansum which is considered as the efficient natural source of PAT and its contamination in
197 apple juice is a worldwide problem [46,60]. The report revealed that approximately 50% of
198 the analyzed samples were comparatively high detectable PAT levels in apple juice globally
199 while organic apples have higher PAT contamination in baby food compared to conventional
200 apples [35]. PAT represents various acute and chronic toxicity, such as nausea, vomiting, and
201 gastrointestinal disturbances acutely, while in chronic cases, damage to kidney and liver,
202 immunosuppression, carcinogenicity, and genotoxicity have been reported [61].

203 2.8 Ergot alkaloids (EAs)

204 EAs are compounds produced as a toxic mixture of alkaloids in the sclerotia (purplish or
205 black structures) of Claviceps and Neothyphodium species usually common pathogens of
206 various grass species and cereal crops [62]. The recent development of grain cleaning
207 methods notably mitigate ergotism in human whereas yet is an important veterinary issue
208 since have been used as pharmaceutical preparation [15,49]. The most prominent of EAs
209 include compounds such as ergotamine, ergometrine, ergocristine, ergocryptine, ergocornine,
210 and ergosine which usually co-appear in contaminated feed [62]. Toxicity of EAs in humans
211 can cause hallucinations, convulsions, fever, distorted perception, acute burn, agalactia
212 wherein animals, include gangrene, abortion, convulsions, suppression of lactation and
213 hypersensitivity [47,62,63]. An outbreak of ergot toxicoses reported the cause of death of
214 eight calves fed a pelleted creep feed in the USA [64].

215 3. Current methods in the analysis and structural elucidation of mycotoxins

216 Analysis of mycotoxin in foods is a crucial practice to ensure food security and removal and
217 control of health risks by contaminated foods. Several detection methods have been
218 developed, among the most common methods currently used are described below.

219 3.1 Chromatographic Techniques (CTs)

220 CTs represent a group of techniques most widely used for quantitative analysis of mycotoxin
221 in food and feed samples which are highly selective, accurate, sensitive, distinctly confirm
222 the positive result and also assist the validity of other methods [31, 65]. High-performance
223 liquid chromatography (HPLC), Thin-layer chromatography (TLC), Gas chromatography
224 (GC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) are commonly
225 used chromatographic techniques for mycotoxin analysis. In China, HPLC coupled with
226 ultraviolet (UV), diode array (DAD), fluorescence detector (FLD) or mass spectrometry (MS)
227 detector has been used to detect AFT, OTA, DON, ZEN, FUM, CIT and PAT and by
228 coupling Liquid chromatography techniques to mass spectrometry (LC-MS/MS) has been
229 used for the simultaneous detection of multiple (hundreds) mycotoxins in various products
230 [31,66]. TLC is cost-effective, simple and suitable for rapid screening of common mycotoxin,
231 but the lack of automation limits its use; moreover, GC coupled with electron capture (ECD),
232 flame ionization (FID) or MS detector have been applied for volatile mycotoxins (TCT and
233 PAT) also limits its commercial use [31,67].

234 3.2 Immunological Methods

235 3.2.1 Enzyme-linked immunosorbent assay (ELISA)

236 ELISA has been a commonly used immunoassay method for the detection of major
237 mycotoxins in a large number of food samples. It can be performed by direct, indirect and
238 competitive inhibition method where an enzyme-labeled primary and secondary antibody
239 reacts with antigen in direct and indirect detection respectively; moreover, in competitive
240 inhibition method, unlabeled antigens from samples and enzyme conjugate compete to bind
241 with an antibody directed against the specific mycotoxin [65]. This method has the advantage
242 of a relatively low limit of detection, highly specific, minimal cleanup procedure, high
243 sample yield with low sample volume and ease of application; meanwhile possibility of a
244 false positive and false negative result, single-use of kits and unsuitable for complex matrices
245 restricts its use for field-testing [68].

246 3.2.2 Lateral Flow Immunoassay (LFIA)

247 LFIA has designed using the principle of ELISA available as commercial kits for the visual
248 qualitative detection of a specific mycotoxin. This method is a low-cost, very simple, rapid,
249 one-step screening tool for mycotoxin analysis at the field level, besides the possibility of
250 semi-quantitative detection using a portable photometric strip reader [65,69]. A multiplex
251 LFIA has designed and optimized that provides both qualitative and quantitative for
252 coinciding in situ determination of AFB1, ZEN, and OTA in grain [65].

253 3.2.3 Fluorescence Polarization Immunoassay (FPIA)

254 As compared to ELISA and LFA, the FPIA needs only a few minutes without separation and
255 washing methods and indirectly measure the quantitative detection of mycotoxin by
256 determining the rate of a fluorophore (tracer) in the solution where free mycotoxin on the
257 sample compete with mycotoxin labeled with the tracer towards a specific antibody [65,70].
258 Nowadays commercial FPIA kits are available which can be used for monitoring AFT, DON,
259 and FUM in cereal at large-scale; besides FPIA could be used as a screening method for the
260 simultaneous detection of the ZEN in naturally contaminated maize sample [70].

261 3.3 Biosensor methods

262 Compared with above conventional techniques, biosensors methods have been proved as
263 potential to allow rapid, highly sensitive, robust, portability, real-time detection capability,
264 high-throughput, and cost-effective quantitative technology in testing food samples [71,72].
265 Up to now development of new and emerging advancement in the analysis of mycotoxin,
266 nanomaterials and biosensor fabrications technology as sensing receptors for mycotoxin,
267 transducer technology at the micro/nanoscale as multiplex analysis and nano-tracking
268 systems, micro and nanosystems as food tracking, electrochemical immunosensors,
269 fluorescent nitrogen-doped carbon dots, lab-on-a-chip devices, microarray, and
270 nanotechnology can be used [65,71].

271

272 4. Prevention and control of mycotoxins contaminations

273 It has been accepted that the prevention of different mycotoxins contamination is the
274 primary measure and alternative over the other control methods. Still numerous physical
275 and chemical detoxification control strategies have been established to prevent the growth of
276 toxigenic fungus and mycotoxin contamination, few strategies fulfill the standards due to
277 their heavy cost, bio-safety risk, losses in the nutritional quality and the palatability of the
278 products or limited binding effect. Therefore it is necessary to develop appropriate
279 detoxification methods to ensure food safety for human consumption. Table 3 summarizes
280 the advantages and disadvantages of different mycotoxin detoxifying agents. In this article,
281 we discussed below the biological detoxification methods and innovations for control and
282 mitigation of mycotoxins problem.

283 4.1 Biological detoxification

284 Biological detoxification refers to the degradation or enzymatic transformation of mycotoxins

285 into less toxic compounds comprising acetylation, glycosylation, ring cleavage, hydrolysis,
286 deamination, and decarboxylation.

287 4.1.1 Mycotoxin modifiers

288 Control of mycotoxicoses with the application of microorganisms and their enzymes is called
289 mycotoxin modifiers which biotransform mycotoxins into less toxic metabolites. They are
290 classified as -

291 4.1.1.1 Use of Microorganisms

292 Biological approaches for mycotoxins decontamination by using microorganisms and specific
293 kinds of isolated yeasts have been used effectively for the management of mycotoxins in food
294 and feeds. Mechanisms in the removal of toxins by microorganisms are still investigated and
295 successful results have been obtained related to this method in recent years. A wide range of
296 microorganisms including bacteria, fungi, and yeasts have proved biodegradation capacity.

297 4.1.1.1.1 Bacteria

298 Mycotoxin degrading bacteria have been isolated from different sources like rumen and
299 intestinal flora, soil, and even water. Lactic acid bacteria (LAB) namely Lactobacillus,
300 Bifidobacterium, Propionibacterium, and Lactococcus are significantly bound with AFB1
301 and AFM1, whereas, Lactobacillus rhamnosus was found as the excellent binding capability
302 with AFB1 in contaminated wheat flour during the bread-making process [73,74]. Therefore
303 special attention pay to LAB as they prevent the growth of molds and mycotoxins, improving
304 the feed utilization via specific hydrolytic enzymes production that decomposes
305 carbohydrates as well as increases host's enzyme activity, such as β-galactosidases,
306 saccharase, and maltase [75]. In recent reports Bacillus licheniformis CFR1 showed more
307 than 90% degradation of AFB1 and a newly isolated bacterial strain Lysinibacillus sp. ZJ-
308 2016-1 from chicken large intestine proved useful in the removal of ZEN in Luria Bertani
309 (LB) broth within 48 h [76,77]. Interestingly, B. subtilis ANSB01G isolated from normal
310 broiler intestinal chyme could efficiently reduce ZEN in naturally contaminated corn,
311 distiller's dried grains with solubles (DDGS) and swine complete feed [78]. Pseudomonas
312 aeruginosa N17-1 were able to degrade AFB1, AFB2, and AFM1 in Nutrient Broth medium,
313 while cell-free supernatants of P. putida DSM 291T and KT2442 were able to remove OTA
314 [79,80]. In another report, P. alcaliphila TH-C1 and P. plecoglossicida TH-L1, isolated from
315 soil showed ZEN degradation ability [81]. A bacterium Devosia mutans 17-2-E-8 from an
316 agricultural soil was capable of transforming DON to the less toxic product in vitro and in
317 vivo studies [82]. In china a novel bacterium, Eggerthella sp. DII-9 has been isolated recently
318 from chicken intestines that are capable of detoxifying TCTs (DON, HT-2, T-2 triol, and T-2
319 tetraol) with high de-epoxidation efficiency [83].
320 4.1.1.1.2 Fungi and Yeast

321 Fungal species, Aspergillus, Alternaria, Absidia, Armillariella, Candida, Dactylium, Mucor,
322 Penicillium, Peniophora, Pleurotus, Trichosporon, Rhizopus have been shown the ability to
323 degrade different mycotoxins [84]. The appropriate quantity of yeast as feed additive
324 decreases the bioavailability of mycotoxins in the GI tract which is removed through feces
325 [85]. In vitro studies revealed that, yeast cell wall containing beta-glucans and mannan
326 oligosaccharides can efficiently bind with AFB1 up to 90%, depending on the level [86].
327 Distillery yeast sludge (DYS), composed of Saccharomyces cerevisiae, Candida parapsilosis,
328 and Candida guilliermondii are a rich source of proteins, lysine, tryptophan, phosphorus,
329 crude fiber, iron, mannan, glucan and ascorbic acid that formed as a by-product of molasses
330 fermentation. Research report suggested that DYS possesses the ability to prevent the
331 absorption of mycotoxin in GI tract can be used as a poultry feed additive as it partially
332 ameliorated the immunotoxic effects of mycotoxins [87]. Aspergillus parasiticus (NRRL
333 2999 and NRRL 3000) actively degraded AFTs, A. tubingensis NJA-1, isolated from soil,
334 showed the ability to degrade DON, A. niger degrades OTA to the less toxic compound OTα,
335 also capable to remove ZEN by incubation in contaminated culture medium after 24 hrs [88].
336 Trichosporon mycotoxinivorans and Rhizopus isolates (stolonifer, oryzae, homothallicus, and
337 microspores) showed high potentiality to degrade ZEN and OTA as less toxic compound
338 [89,90]. A new strain of T. mycotoxinivorans capable of degrading ZEN and OTA into the
339 nontoxic OTα which has been commercially used to detoxify OTA in animal and poultry diet
340 [40,91]. Yarrowia lipolytica yeast showed the highest OTA degradation activity at 280C
341 incubation temperature with pH level 4 [66]. Phaffia rhodozyma and Xanthophyllomyces
342 dendrorhous yeasts also possess OTA degradation activity but their practical application yet
343 limited due to lack of potential data.
344 Table 3: Comparison of different mycotoxin detoxifying products [18, 92-96]
Bacteria Fungus Yeast Enzymes Chemicals Physical
Bacillus licheniformis, B. natto, B. Peroxidase, Laccase,
345 subtilis, Brevibacterium casei, B. Myxobacteria aflatoxin Automated removal of damaged
linens, B. iodinum, Nocardia degrading enzyme Ammonia/ Ammonia kernels, Fluorescence sorting,
corynebacteroides, Mycobacterium (MADE), with calcium hydroxid, Flotation, Pressure cooking,
fluoranthenivorans, Rhodococcus Carboxylesterase B & Ozone, Sodium Microwave heating, Rinsing,
346 Products erythropolis , Mycococcus fulvus, Aspergillus Trichosporon aminotransferase, bisulphate, Hydrogen Nixtramalization, Roasting,
Pseudomonas putida, Serratia niger mycotoxinivorans Cytochrome P450 peroxide, Sodium Wet-milling, Sunlight, heat
spp, Stenotrophomonas system bicarbonate, Sodium processing, UV light irradiation,
347 maltophilia, Brevundimonas spp, (Ddna + Kdx +KdR), chloride, Calcium Gamma radiation, Pulsed light
Klebsiella spp, Cellulosimicrobium Ochratoxinase, hydroxide technology, Electron beam
spp, Lactic acid bacteria, Lactono hydrolase, irradiation (EBI)
348 Pediococcus parvulus, 2cys-peroxiredoxin

Toxin- AFB1, OTA, FB1, DON, AFT, OTA, FUM, DON, AFT, OTA, FUM, DON, T-2,
AFB1, OTA, FB1, DON, ZEN OTA OTA, ZEN
specific ZEN ZEN ZEN, PAT,
349
• High specificity • High
• Non-invasive
• Safe specificity
• Product stability
• Fermentation process • safe • Moderate
350 • Safe
Advantage • Application for food and feed • No loss of specificity
• Rapid & highly
• Comparatively rapid process appearance or
effective
• Cheap food quality
351 • Incomplete
• Loss of quality of
• Toxic residue food or feed
352 • Loss of • Discoloration & off-
• Sometimes do not show good efficacies in field conditions nutritional flavor
• Long incubation time required for detoxification (more than • Instability quality of food • Cross-contamination
353 Disadvantage
72 h) • Not applicable & feeds • Not effective for all
• Incomplete degradation, non-adaptation to typical food for all types of • Corrosive food items
fermentations & culture pigmentation mycotoxins • Expensive • Development of
354 • Expensive at startup • Development mutant & resistant
of resistance strains
• Expensive
• Residual effects
355

356

357
358 4.1.1.2 Use of Enzymes

359 Specific enzymes such as oxidase, peroxidase, laccase, reductase, esterase, carboxylesterase,
360 aminotransferase, lactono hydrolase having the capacity of degrading mycotoxins have been
361 purified from microbial systems [95]. An enzyme peroxidase from Aspergillus (flavus,
362 parasiticus) and a horseradish peroxidase enzyme from Raphinus sativa plant have been
363 shown AFB1 degradation activity [69]. Enzymatic degradation by extracellular extract from
364 Rhodococcus erythropolis culture along with laccase enzyme from several fungal species
365 showed effective degradation of AFB1 [97]. In a study, two genes of soil bacteria
366 Sphingopyxis sp. MTA 144 were identified and recombinant enzymes were produced which
367 degraded FB1 by two consecutive steps, firstly FB1 is hydrolyzed to HFB1 by
368 carboxylesterase and then it deaminated by aminotransferase to further less toxic compound
369 [98]. A purified extracellular enzyme, myxobacteria aflatoxin degradation enzyme (MADE),
370 from bacterium Myxococcus fulvus ANSM068 showed much degradation ability toward
371 AFG1 (96.96%) and AFM1 (95.80%) [99]. The enzyme epoxidases detoxifies DON to its de-
372 epoxy form DOM-1 [100]. Brevibacterium species (B. epidermidis, B. iodinum and B. casei)
373 are capable of degrading OTA, due to release of highly active proteolytic carboxypeptidase
374 enzymes [80]. In a recent report revealed that OTA was significantly (74.8-84.9%) reduced
375 by a carboxypeptidase and peptides present in liquid cultures of Bacillus subtilis CW14 [101].

376 4.1.2 Mycotoxin binders

377 Mycotoxin binders also known as adsorbents or sequestering agents have been used to
378 decontaminate animal feed by binding the mycotoxin and inhibit their absorption in the
379 gastrointestinal tract, where the bounded toxins can be eliminated via feces or urine of animal
380 [20,102]. Both inorganic (hydrated sodium calcium aluminosilicates, zeolites, bentonites,
381 fuller's earth, diatomaceous earth, activated charcoal, kaolin, sepiolitic clay, cholestyramine)
382 and organic binders (alfalfa fibre, oat fibers, extracted cell wall fraction of Saccharomyces
383 cerevisiae, beta-D-glucan fraction of yeast cell wall) have been using for the control of toxin
384 in diet [20,86,92]. Hydrated sodium calcium aluminosilicates inhibits the toxicity of AFTs in
385 domestic animals along with decreases the AFM1 level in cow and goat milk whereas,
386 zeolites can adsorb AFB1 and ZEA from feed [92]. Activated charcoal significantly removed
387 OTA and PAT from contaminated wine and apple juice respectively [12]. In the recent report
388 found that the body weight of broiler birds were increased 63%–100% by incorporation of
389 activated charcoal, bentonite, and fuller’s earth to aflatoxin-contaminated feed [102]. The
390 binding efficiency of yeast has been mentioned earlier in section 4.1.1.1.2.

391 4.1.2 Herbal products for the amelioration of toxic effects of mycotoxins

392 Herbal products such as spices, plant extracts, aromatic oils (lipophilic compounds from
393 terrestrial herbs), primary olives (non-water solvents) are mixed with animal feed to increase
394 growth performance and quality of the product. Research report showed that ethanolic extract
395 of Cassia Senna (vegetable laxative) and methanol extract of Cassia tora (Naphtopyrone
396 glycosides and anthraquinone aglycones) decreases the mutagenic effect of AFB1 in vitro;
397 whereas methanol extract of Piper argyrophyllum leaves and Thonninga sanguinea extract
398 found to be ameliorated the genotoxicity and hepatotoxicity effect of AFB1 in rat
399 respectively [103]. Natural herbs such as green tea, cinnamon, chamomile, ginger, black
400 pepper, coriander, black seed, licorice, garlic, onion, fenugreek seeds, basil seeds, and
401 roquette seeds can detoxify mycotoxins [104,105]. In a study report, it is found that turmeric
402 extract (Curcuma longa) can ensure protection against the adverse effects of AFT on the
403 performance of broiler birds [106]. In another study, herbal feed additives (Silybum
404 marianum, Withania somnifera) showed hepatoprotective and nephroprotective effect on
405 OTA-contaminated feed in broiler chicks [107]. The aqueous extract of Ocimum tenuiflorum
406 (aromatic perennial plant) is found to be effective in inhibiting the AFB1 synthesis in the
407 toxigenic strain of A. flavus whereas seeds of Ajowan [T. ammi (L.) Sprague ex Turrill] can
408 degrade AFG1 [108,109]. Medicinal plants, black cumin (Nigella sativa), clove (Eugenia
409 caryophyllata) and thyme (Thymus vulgaris) extracts have efficacy in suppressing fungal
410 growth and toxin production by Fusarium verticilloides and A. flavus isolates [110]. In a
411 recent report leaves extracts from sweet passion fruit (Passiflora alata), araçá (Psidium
412 cattleianum), rosemary (Rosmarinus officinalis) and oregano (Origanum vulgare) efficiently
413 degrade AFB1 in vitro [111].

414 5. Innovative approaches

415 5.1 Nanobiotechnology

416
417 This technique apparently a novel promising, effective and low-cost strategy that can offer
418 green and eco-friendly for the control mycotoxigenic fungi and mycotoxins in the agriculture
419 and food industry. The nanomaterials such as nanosilver (AgNPs), Zinc Oxide nanoparticles
420 (ZnO-NPs), Selenium nanoparticles (SNP), Copper nanoparticles (CuNPs), magnetic
421 nanoparticles like surface active maghemite nanoparticles (SAMNs), nano clay, nanogel, nano
422 binders, and nanodiamonds can bind and remove mycotoxins or pathogens in food and feed
423 [112]. AgNPs treatment found very effective against aflatoxigenic and ochratoxigenic fungi
424 and AF and OTA accumulation in maize-based medium [113]. Selenium nanoparticles (SNP)
425 derived from Trichoderma harzianum JF309 showed more growth inhibition of fungus and
426 reduced DON (76%) and FB1 (63%) [114]. The application of ZnO-NPs in food systems is
427 compelling in preventing the growth of mycotoxigenic fungi (Aspergillus spp., Fusarium spp.,
428 Penicillium spp.) and production of AFB1, OTA and FB1 [115]. The research demonstrated
429 that CuNPs showed high antifungal activity against Curvularia lunata, Alternaria alternata
430 and Fusarium (culmorum, oxysporum, graminearum) fungi [112]. SAMNs are efficient in
431 CIT binding, magnetic carbon nano compound produced from maize waste showed 90%
432 adsorption of AFB1 and chitosan-coated Fe3O4 particles are promising adsorbents for patulin
433 adsorption in the fruit juice industry [116,117]. Another nano-based approach could be the
434 use of green nanofungicides formulations developed by phytochemicals (catechols, eugenol,
435 essential oils, phloretin, hexanal, d-limonene, menthol, caffeic acid, thymol, tannins, etc.)
436 extracted from plant materials with antibacterial and antifungal activity. The advantage of
437 this method is it is easy and cheap to prepare from natural constituents of plants that present
438 no toxicity to human and animal health. Recent studies found that nanomaterials loaded with
439 phytochemicals can be used to inhibit the production of toxigenic fungus and reduce the
440 mycotoxin contamination in the food chain [118].
441 5.2 Antibody-mediated technology
442 Development of monoclonal and recombinant fungal-specific antibodies expressed in plants
443 can limit the distribution of the fungal pathogens in the field and ultimately minimize the
444 mycotoxin-production load. Monoclonal antibodies (Mabs 213221) with high binding
445 specificity to Fusarium mycotoxins were capable of binding to a wide variety of fumonisin-
446 carbohydrate derivatives considered as an appropriate tool for detecting modified FB1 in
447 maize [119]. Nevertheless, Mabs production and maintenance are difficult due to the high
448 cost and specialized cell culture facilities are required. The phage display technology which
449 generates recombinant single-chain antibodies specific to antigens displayed on the Fusarium
450 cell surface similar to Mabs can be the alternative choice [120]. Research report revealed that
451 these antibodies react strongly with cell wall-bound proteins and bind to the surface
452 components of F. asiaticum [121]. In this method, antibody binding domain (Fv) of natural
453 antibodies are formed, called a single-chain variable fragment (scFV) which has been used
454 for the protection of plants against pathogenic fungi. A chicken-derived phage display
455 Fusarium-specific antibody (scFv) is identified that reacts significantly with cell wall-bound
456 proteins of Fusarium pathogens and remarkably enhanced in transgenic Arabidopsis thaliana
457 plants [122]. In a recent report, the use of antibody-decorated magnetic nanoparticles showed
458 purification of an average of 80% of the ZEN and AFB1 from mycotoxin-contaminated feed
459 mixture [1]. Expression of antibody-mediated resistance in crops against initial infection at
460 the field could be a control strategy for neutralizing and blocking fungal toxins.
461
462 5.3 Genetic improvement of crops
463
464 Mycotoxin contamination may both pre- and post-harvest stage which can be reduced greatly
465 by developing disease-resistant traits through more sophisticated biotechnological approaches
466 during the pre-harvest stage. Recently modern transgenic techniques such as Host-induce
467 gene silencing (HIGS), RNA interference (RNAi), microRNA (miRNA)- or artificial
468 microRNA (amiRNA)- mediated gene silencing, designer transcription activator-like effector
469 (dTALE)-mediated up or down-regulation of gene expression, Zn-Finger nucleases, mega-
470 nucleases, transcription activator-like effector nucleases (TALEN), clustered regularly
471 interspaced short palindromic repeats (CRISPR)/Cas9, and oligonucleotide-directed
472 mutagenesis (ODN)-based gene-editing techniques can be applied for development of
473 mycotoxin resistant plant. In the HIGS method, pathogenic fungi are directed by the host
474 plant to down-regulate the expression of its own genes, without requiring the host plant to
475 express a remote protein [123]. An RNAi-based approach for mycotoxin resistance in the
476 crop, use of RNAi as counteracting the vital gene essential for fungus and toxin production.
477 The transgenic crop would be developed with self-complementary hairpin RNAs of
478 antifungal genes resulting in small interfering RNAs (siRNAs) by the host plant's DICER-like
479 enzymes which have been efficiently taking up the transgenic tobacco generating gus siRNA
480 by Fusarium verticillioides for silencing of the targeted gus gene [124]. In this method, using
481 dual silence Bc-Dcl1 and Bc-Dcl2 genes revealed a substantial decrease of fungal
482 pathogenicity and growth to a wide range of plant may be considered as a promising target
483 for control of mycotoxins [125]. In another study silencing of five AFT- silencing genes by
484 RNA interference (RNAi) in peanut plants showed up to 100% reduction in AFB1 and AFB2
485 when inoculated with aflatoxigenic A. flavus [126]. In a study report, the role of miRNA was
486 revealed that overexpression of Osa-miR7696 in transgenic rice plants gives rise to resistance
487 against rice blast fungus Magnaporthe oryzae [127]. Zinc-finger nucleases (ZFNs) and
488 transcription activator-like effector nucleases (TALENs) have been used for genome edition
489 of many crops but due to expensive and complexity of these techniques CRISPR/Cas system
490 which allows targeted modification of different crops genome sequence to generate
491 mycotoxin resistant varieties is superior because of its specificity and cheap, and it can be
492 applied in crop improvement [128]. Genetically modified maize expressing the Bacillus
493 thuringiensis (Bt) toxin anti-insecticidal cry1A(b) gene showed efficacy to reduce its
494 contamination with Fusarium mycotoxins (FUM, DON, ZEN) in grain [129].
495
496 5.4 Genetically modified animals (GMA)
497
498 Genetic engineering has the possibility to ameliorate the health and welfare of agricultural,
499 food and laboratory animals such as cattle, pigs, chickens, goats, sheep, dogs, cats, fish, rats,
500 and mice. The feasibility of creating GMA with the insertion of transgenes targeting specific
501 pathogens into the genomes of host animals such as mastitis-resistant livestock, pigs resistant
502 to African swine fever and chicks resistant to Avian influenza (H5N1) has been improved
503 [130-132]. The new strategy genetic restoration where germ-line modification in host animals
504 by generating targeted gene via zinc-finger nucleases, TALENs or CRISPR-Cas9 could be a
505 noble approach for the development of the disease-resistant animal. The TALENs method is
506 very effective where specially coded enzymes called TALENs are used to split or cut out
507 specific target DNA segments will be replaced by new segments, thereby allowing the
508 researchers to insert the preferred traits into the DNA of the subject. In the CRISPR method,
509 a DNA-snipping enzyme called Cas9 involved in the defense mechanisms of bacteria and
510 archaea is used, which cuts out specific segments of DNA following new segments are
511 inserted to fill the gaps. This mutant cell can then divides and multiply through mitosis,
512 creating more cells with the desired traits. The production of GMA can have a great impact
513 on the livestock and food chains are anticipated to economic benefits for the farmers,
514 producers, and consumers. However, consumer concerns about genetically modified animals
515 about their long-term impacts on health and environment should not be overlooked; such
516 concerns are addressed seriously if society is to benefit from new developments.
517

518 6. Implication and outlook

519 Mycotoxins represent a major risks to the food chain associated with human and animal
520 health aspects therefore early and rapid detection will help in the elimination of toxins for
521 preventing health problems and protecting life. Due to regulatory, toxicological and
522 consumer protection use of detoxification agent is limited in food and feed industries. So far
523 most of the research focuses on the biological detoxification methods more attention should
524 be given for the practical evaluation of these microorganisms or their enzymes in food and
525 feeds. However conventional decontamination methods are continually improving, recent
526 research results are looking for innovative solutions. Therefore, it draws attention to the need
527 for prevention and control strategies such as A. Control of mycotoxin by gene editing crop B.
528 Rapid and cheap test technology C. Mycotoxin inhibits technology D. Nano antibody that
529 reduces contamination in the food chain. Development of fungi resistant crops by genetic
530 engineering technology to identify the mycotoxin detoxification gene to develop transgenic
531 resistance to mycotoxin found to be a good choice. The new nanotechnology has the potential
532 to many aspects of agriculture, livestock, and the food industry; specially nanoparticles can
533 be applied as antifungal agents to minimize the health effects of mycotoxins. However, this
534 technology is still in the preliminary stages, a clear perception of possible health outcome of
535 nanoparticles is unknown thereby limits its application in regards to food security hence more
536 research need to be focused. Screening microbial population from various mycotoxin-
537 contaminated environments assume to be a promising approach for mycotoxin degradation
538 which can be improved by coupling innovative techniques and approaches, such as
539 enrichments, highly selective media, PCR-DGGE bacterial profiles and functional
540 metagenomics [95]. It is also a noble approach to develop research focusing on probiotic
541 bacteria and enzyme products for the effective detoxification of mycotoxin which can be
542 applicable as feed additives in the commercial sector [133]. Considering this application of
543 enzymes and cloning of genes through genetic engineering to develop genetically modified
544 species suitable for the industrial scale of enzyme production and purification used in food
545 production could be an alternative technology for mycotoxins detoxifications in the human
546 and animal food chains [134]. Combined with the advanced biotechnology, antibody-
547 mediated resistance to initial infection and spreading the fungal pathogen on susceptible
548 grains offers new scope for the establishment of an environmentally friendly strategy for the
549 control of mycotoxins. Special importance should be focused on the advancement of cost-
550 effective, convenient and easy handling instruments and methods for the detection of
551 mycotoxin at the filed condition. Further research also needs to be highlighted on the
552 epidemiological surveillance and generation of data dealing with the toxic effects of
553 mycotoxin, especially in humans.

554 7. Competing interest

555 The authors declare no competing interests.

556 8. Funding
557 This work was supported by the [Taishan Scholar Foundation of Shandong Province] under
558 Grant [No. ts201511084]; by the [Shandong Double-Hundred Talent Plan] under Grant
559 [ No.201912018 ].
560

561 9. References
562 1. Horky, P., Skalickova, S., Baholet, D., & Skladanka, J. (2018). Nanoparticles as a Solution for Eliminating the Risk of
563 Mycotoxins. Nanomaterials, 8(9), 727. doi:10.3390/nano8090727
564 2. Ukwuru, M.U., Ohaegbu, C.G., & Muritala, A. (2018). An Overview of Mycotoxin Contamination of Foods and Feeds. J
565 Biochem Microb Toxicol 1: 101.
566 3. Grenier, B., & Oswald, I. (2011). Mycotoxin co-contamination of food and feed: meta-analysis of publications describing
567 toxicological interactions. World Mycotoxin Journal, 4(3), 285–313. doi:10.3920/wmj2011.1281
568 4. Levy, M. B., & Fink, J. N. (2004). Toxic Mold Syndrome. Advances in Applied Microbiology, 275–288. doi:10.1016/s0065-
569 2164(04)55010-4
570 5. Milićević, D. R., Škrinjar, M., & Baltić, T. (2010). Real and Perceived Risks for Mycotoxin Contamination in Foods and Feeds:
571 Challenges for Food Safety Control. Toxins, 2(4), 572–592. doi:10.3390/toxins2040572
572 6. Eshetu, E., Adugna, H., & Gebretensay, A., (2016). An Overview on Major Mycotoxin in Animal: Its Public Health Implication,
573 Economic Impact and Control Strategies. Journal of Health, Medicine and Nursing 25:64-73.
574 7. Wang, Y., Zhao, C., Zhang, D., Zhao, M., Zheng, D., Peng, M., … Cui, Z. (2018). Simultaneous degradation of aflatoxin B 1 and
575 zearalenone by a microbial consortium. Toxicon, 146, 69–76. doi:10.1016/j.toxicon.2018.04.007
576 8. Pitt, J. I., & Miller, J. D. (2016). A Concise History of Mycotoxin Research. Journal of Agricultural and Food Chemistry, 65(33),
577 7021–7033. doi:10.1021/acs.jafc.6b04494
578 9. Fernandes, T. H., Ferrão, J., Bell, V., & Chabite, I. T. (2017). Mycotoxins, Food and Health. J Nutrition Health Food Sci, 5(7):1-
579 10. doi: 10.15226/jnhfs.2017.001118
580 10. Simion, V. E., Bogdan, A. T., Andronie, V., Ipate, I., Pârvu, M., Covaci, B., Mitrănescu, E., & Andronie, C. (2011). Macro and
581 microclimate – from beneficial to noxious action on the animals. 6th IASME / WSEAS International Conference on Energy &
582 Environment (EE'11), Recent Researches in Energy & Environment Cambridge, Uk February 23-25, 201. ISSN: 1792-8230
583 ISBN: 978-960-474-274-5
584 11. Fokunang, C. N., Tembe-Fokunang, E. A., Tomkins, P., & Barkwan, S. (2006). Global Impact of Mycotoxins on Human and
585 Animal Health Management. Outlook on Agriculture, 35(4), 247–253. doi:10.5367/000000006779398263
586 12. Zaki, M. (2012). Mycotoxins in animals: Occurrence, effects, prevention and management. Journal of Toxicology and
587 Environmental Health Sciences, 4(1), 13–28. doi:10.5897/jtehs11.072
588 13. Milićević, D., Nastasijevic, I., & Petrovic, Z. (2016). Mycotoxin in the food supply chain—implications for public health
589 program. Journal of Environmental Science and Health, Part C, 34(4), 293–319. doi:10.1080/10590501.2016.1236607
590 14. Vanhoutte, I., Audenaert, K., & De Gelder, L. (2016). Biodegradation of Mycotoxins: Tales from Known and Unexplored
591 Worlds. Frontiers in Microbiology, 7. doi:10.3389/fmicb.2016.00561
592 15. Ashiq, S. (2014). Natural Occurrence of Mycotoxins in Food and Feed: Pakistan Perspective. Comprehensive Reviews in Food
593 Science and Food Safety, 14(2), 159–175. doi:10.1111/1541-4337.12122
594 16. Cary, J., Rajasekaran, K., Yu, J., Brown, R., Bhatnagar, D., & Cleveland, T. (2009). Transgenic approaches for pre-harvest
595 control of mycotoxin contamination in crop plants. World Mycotoxin Journal, 2(2), 203–214. doi:10.3920/wmj2009.1138
596 17. Gurbuz, Y., Hussein, A., & Ozkose, E. (2019). Determination of AFLD and AFLQ genes responsible for aflatoxin formation in
597 some livestock concentrated feeds. Pak Vet J, 39(2): 163-168. doi:10.29261/pakvetj/2019.057
598 18. Ismail, A., Gonçalves, B. L., de Neeff, D. V., Ponzilacqua, B., Coppa, C. F. S. C., Hintzsche, H., … Oliveira, C. A. F. (2018).
599 Aflatoxin in foodstuffs: Occurrence and recent advances in decontamination. Food Research International, 113, 74–85.
600 doi:10.1016/j.foodres.2018.06.067
601 19. Li, H., Li, S., Yang, H., Wang, Y., Wang, J., & Zheng, N. (2019). l-Proline Alleviates Kidney Injury Caused by AFB1 and
602 AFM1 through Regulating Excessive Apoptosis of Kidney Cells. Toxins, 11(4), 226. doi:10.3390/toxins11040226
603 20. Abdallah, M. F., Girgin, G., & Baydar, T. (2015). Occurrence, prevention and limitation of mycotoxins in feeds. Animal
604 Nutrition and Feed Technology, 15: 471-490. doi: 10.5958/0974-181X.2015.00048.7
605 21. Enyiukwu, D. N., Awurum, A. N., & Nwaneri, J. A. (2014). Mycotoxins in Stored Agricultural Products: Implications to Food
606 Safety and Health and Prospects of Plant-derived Pesticides as Novel Approach to their Management: Greener Journal of
607 Microbiology and Antimicrobials, 2 (3): 032-048.
608 22. Liew, W.-P.-P., & Mohd-Redzwan, S. (2018). Mycotoxin: Its Impact on Gut Health and Microbiota. Frontiers in Cellular and
609 Infection Microbiology, 8. doi:10.3389/fcimb.2018.00060
610 23. Bhat, R. V. (2008). Human health problems associated with current agricultural food production. Asia Pac J Clin Nutr, 17 Suppl
611 1:91-4.
612 24. Liu, Y., & Wu, F. (2010). Global Burden of Aflatoxin-Induced Hepatocellular Carcinoma: A Risk Assessment. Environmental
613 Health Perspectives, 118(6), 818–824. doi:10.1289/ehp.0901388
614 25. Lozano, M. C., & Diaz, G. J. (2006). Microsomal and cytosolic biotransformation of aflatoxin B1 in four poultry species. British
615 Poultry Science, 47(6), 734–741. doi:10.1080/00071660601084390
616 26. Sana, S., Anjum, A.A., Yaqub, T., Nasir, M., Ali, M.A., Abbas, M. (2019). Molecular approaches for characterization of
617 aflatoxin producing Aspergillus flavus isolates from poultry feed. Pak. Vet. J. 39, 169–174. doi: 10.29261/pakvetj/2019.031
618 27. Naseem, M.N., Saleemi, M.K., Abbas, R.Z., Khan, A., Khatoon, A., … Sultan, A. (2018). Hematological and serum biochemical
619 effects of aflatoxin B1 intoxication in broilers experimentally infected with fowl adenovirus-4 (FAdV-4). Pak Vet J, 38(2): 209-
620 213. doi: 10.29261/pakvetj/2018.028
621 28. Man, Y., Liang, G., Li, A., & Pan, L. (2017). Recent Advances in Mycotoxin Determination for Food Monitoring via Microchip.
622 Toxins, 9(10), 324. doi:10.3390/toxins9100324
623 29. Hojnik, N., Cvelbar, U., Tavčar-Kalcher, G., Walsh, J., & Križaj, I. (2017). Mycotoxin Decontamination of Food: Cold
624 Atmospheric Pressure Plasma versus “Classic” Decontamination. Toxins, 9(5), 151. doi:10.3390/toxins9050151
625 30. Eshelli, M., Qader, M., Jambi, E., Hursthouse, A., & Rateb, M. (2018). Current Status and Future Opportunities of Omics Tools
626 in Mycotoxin Research. Toxins, 10(11), 433. doi:10.3390/toxins10110433
627 31. Alshannaq, A., & Yu, J.-H. (2017). Occurrence, Toxicity, and Analysis of Major Mycotoxins in Food. International Journal of
628 Environmental Research and Public Health, 14(6), 632. doi:10.3390/ijerph14060632
629 32. Atanda S. A. (2011). Fungi and mycotoxins in stored foods. African Journal of Microbiology Research, 5(25).
630 doi:10.5897/ajmr11.487
631 33. Smith, M.-C., Madec, S., Coton, E., & Hymery, N. (2016). Natural Co-Occurrence of Mycotoxins in Foods and Feeds and Their
632 in vitro Combined Toxicological Effects. Toxins, 8(4), 94. doi:10.3390/toxins8040094
633 34. JH, D. (2015). The Occurrence, Properties and Significance of Citrinin Mycotoxin. Journal of Plant Pathology & Microbiology,
634 6(11). doi:10.4172/2157-7471.1000321
635 35. Marin, S., Ramos, A. J., Cano-Sancho, G., & Sanchis, V. (2013). Mycotoxins: Occurrence, toxicology, and exposure assessment.
636 Food and Chemical Toxicology, 60, 218–237. doi:10.1016/j.fct.2013.07.047
637 36. Munkvold, G. P., (2016). Fusarium Species and Their Associated Mycotoxins. Mycotoxigenic Fungi: Methods and Protocols,
638 Methods in Molecular Biology: Vol. 1542: (Antonio Moretti and Antonia Susca, eds): Springer Science+Business Media LLC,
639 pp: 51–106.
640 37. EFSA Panel on Contaminants in the Food Chain (CONTAM), (2011). Scientific Opinion on the risks for animal and public
641 health related to the presence of T-2 and HT-2 toxin in food and feed. EFSA Journal, 9(12), 2481. doi:10.2903/j.efsa.2011.2481
642 38. Ben Taheur, F., Kouidhi, B., Al Qurashi, Y. M. A., Ben Salah-Abbès, J., & Chaieb, K. (2019). Review : Biotechnology of
643 mycotoxins detoxification using microorganisms and enzymes. Toxicon. doi:10.1016/j.toxicon.2019.02.001
644 39. Awad, W. A., Hess, M., Twarużek, M., Grajewski, J., Kosicki, R., Böhm, J., & Zentek, J. (2011). The Impact of the Fusarium
645 Mycotoxin Deoxynivalenol on the Health and Performance of Broiler Chickens. International Journal of Molecular Sciences,
646 12(11), 7996–8012. doi:10.3390/ijms12117996
647 40. Murugesan, G. R., Ledoux, D. R., Naehrer, K., Berthiller, F., Applegate, T. J., Grenier, B., … Schatzmayr, G. (2015). Prevalence
648 and effects of mycotoxins on poultry health and performance, and recent development in mycotoxin counteracting strategies.
649 Poultry Science, 94(6), 1298–1315. doi:10.3382/ps/pev075
650 41. Osselaere, A., Devreese, M., Goossens, J., Vandenbroucke, V., De Baere, S., De Backer, P., & Croubels, S. (2013).
651 Toxicokinetic study and absolute oral bioavailability of deoxynivalenol, T-2 toxin and zearalenone in broiler chickens. Food and
652 Chemical Toxicology, 51, 350–355. doi:10.1016/j.fct.2012.10.006
653 42. Vidal, A., Mengelers, M., Yang, S., De Saeger, S., & De Boevre, M. (2018). Mycotoxin Biomarkers of Exposure: A
654 Comprehensive Review. Comprehensive Reviews in Food Science and Food Safety. doi:10.1111/1541-4337.12367
655 43. Chilaka, C., De Boevre, M., Atanda, O., & De Saeger, S. (2017). The Status of Fusarium Mycotoxins in Sub-Saharan Africa: A
656 Review of Emerging Trends and Post-Harvest Mitigation Strategies towards Food Control. Toxins, 9(1), 19.
657 doi:10.3390/toxins9010019
658 44. Gelineau-van Waes, J., Voss, K. A., Stevens, V. L., Speer, M. C., & Riley, R. T. (2009). Chapter 5 Maternal Fumonisin
659 Exposure as a Risk Factor for Neural Tube Defects. Advances in Food and Nutrition Research, 145–181. doi:10.1016/s1043-
660 4526(08)00605-0
661 45. Ortiz, C. S., Richards, C., Terry, A., Parra, J., & Shim, W.-B. (2015). Genetic Variability and Geographical Distribution of
662 Mycotoxigenic Fusarium verticillioides Strains Isolated from Maize Fields in Texas. The Plant Pathology Journal, 31(3), 203–
663 211. doi:10.5423/ppj.oa.02.2015.0020
664 46. Edite Bezerra da Rocha, M., Freire, F. da C. O., Erlan Feitosa Maia, F., Izabel Florindo Guedes, M., & Rondina, D. (2014).
665 Mycotoxins and their effects on human and animal health. Food Control, 36(1), 159–165. doi:10.1016/j.foodcont.2013.08.021
666 47. Jeswal, P., & Kumar, D. (2015). Mycobiota and Natural Incidence of Aflatoxins, Ochratoxin A, and Citrinin in Indian Spices
667 Confirmed by LC-MS/MS. International Journal of Microbiology, 2015, 1–8. doi:10.1155/2015/242486
668 48. Magnoli, C. E., Astoreca, A. L., Chiacchiera, S. M., & Dalcero, A. M. (2007). Occurrence of ochratoxin A and ochratoxigenic
669 mycoflora in corn and corn based foods and feeds in some South American countries. Mycopathologia, 163(5), 249–260.
670 doi:10.1007/s11046-007-9005-z
671 49. Bennett, J. W., & Klich, M. (2003). Mycotoxins. Clinical Microbiology Reviews, 16(3), 497–516. doi:10.1128/cmr.16.3.497-
672 516.2003
673 50. EC, (2006). No. 1881/2006. Setting maximum levels for certain contaminants in foodstuffs. Official Journal of the European
674 Union L 364/5. https://www.fsai.ie/uploadedFiles/Reg420_2011.pdf
675 51. Zain, M. E. (2011). Impact of mycotoxins on humans and animals. Journal of Saudi Chemical Society, 15(2), 129–144.
676 doi:10.1016/j.jscs.2010.06.006
677 52. Meucci, V., Razzuoli, E., Soldani, G., & Massart, F. (2010). Mycotoxin detection in infant formula milks in Italy. Food
678 Additives & Contaminants: Part A, 27(1), 64–71. doi:10.1080/02652030903207201
679 53. Yazar, S., & Omurtag, G. (2008). Fumonisins, Trichothecenes and Zearalenone in Cereals. International Journal of Molecular
680 Sciences, 9(11), 2062–2090. doi:10.3390/ijms9112062
681 54. Herzallah, S. M. (2009). Determination of aflatoxins in eggs, milk, meat and meat products using HPLC fluorescent and UV
682 detectors. Food Chemistry, 114(3), 1141–1146. doi:10.1016/j.foodchem.2008.10.077
683 55. FAO, 2004. Worldwide regulations for mycotoxins in food and feed in 2003. FAO food and nutrition papers, Rome, Italy, 81.
684 http://www.fao.org/3/y5499e/y5499e00.htm
685 56. Leblanc, J. C. (2004). Etude de l’alimentation totale en France: Mycotoxines, mineraux et aliments traces. INRA (ed.), Paris.
686 57. Streit, E., Schatzmayr, G., Tassis, P., Tzika, E., Marin, D., Taranu, I., … Oswald, I. P. (2012). Current Situation of Mycotoxin
687 Contamination and Co-occurrence in Animal Feed—Focus on Europe. Toxins, 4(10), 788–809. doi:10.3390/toxins4100788
688 58. Tanaka, K., Sago, Y., Zheng, Y., Nakagawa, H., & Kushiro, M. (2007). Mycotoxins in rice. International Journal of Food
689 Microbiology, 119(1-2), 59–66. doi:10.1016/j.ijfoodmicro.2007.08.002
690 59. Flajs, D., & Peraica, M. (2009). Toxicological Properties of Citrinin. Archives of Industrial Hygiene and Toxicology, 60(4).
691 doi:10.2478/10004-1254-60-2009-1992
692 60. Wright, S. A. (2015). Patulin in food. Current Opinion in Food Science, 5, 105–109. doi:10.1016/j.cofs.2015.10.003
693 61. Moss, M. O. (2008). Fungi, quality and safety issues in fresh fruits and vegetables. Journal of Applied Microbiology, 104(5),
694 1239–1243. doi:10.1111/j.1365-2672.2007.03705.x
695 62. Grusie, T., Cowan, V., Singh, J., McKinnon, J., & Blakley, B. (2018). Proportions of predominant Ergot alkaloids (Claviceps
696 purpurea) detected in Western Canadian grains from 2014 to 2016. World Mycotoxin Journal, 11(2), 259–264.
697 doi:10.3920/wmj2017.2241
698 63. Hulvová, H., Galuszka, P., Frébortová, J., & Frébort, I. (2013). Parasitic fungus Claviceps as a source for biotechnological
699 production of ergot alkaloids. Biotechnology Advances, 31(1), 79–89. doi:10.1016/j.biotechadv.2012.01.005
700 64. MacDonald, S., Chan, D., Lumb, K., Scott, H., Randall, L., Edward, S., … Elliott, C., (2016). Mycotoxin contamination:
701 assessment of risk in livestock systems. Research Review No. 85 AHDB Cereals & Oilseeds, Agriculture and Horticulture
702 Development Board (AHDB).
703 65. Santos Pereira, C., C. Cunha, S., & Fernandes, J. O. (2019). Prevalent Mycotoxins in Animal Feed: Occurrence and Analytical
704 Methods. Toxins, 11(5), 290. doi:10.3390/toxins11050290
705 66. Shi, H., Li, S., Bai, Y., Prates, L. L., Lei, Y., & Yu, P. (2018). Mycotoxin contamination of food and feed in China: Occurrence,
706 detection techniques, toxicological effects and advances in mitigation technologies. Food Control, 91, 202–215.
707 doi:10.1016/j.foodcont.2018.03.036
708 67. Roseanu, A., Jecu, L., Badea, M., Evans, R. W. (2010). Mycotoxins: An overview on their quantification methods, ROM. J.
709 BIOCHEM., 47(1),79–86. http://journal.biochim.ro/archive/n47-1/pdfs_47-1/rjb47-1_06.pdf
710 68. Xie, L., Chen, M., & Ying, Y. (2015). Development of Methods for Determination of Aflatoxins. Critical Reviews in Food
711 Science and Nutrition, 56(16), 2642–2664. doi:10.1080/10408398.2014.907234
712 69. Aiko, V., & Mehta, A. (2015). Occurrence, detection and detoxification of mycotoxins. Journal of Biosciences, 40(5), 943–954.
713 doi:10.1007/s12038-015-9569-6
714 70. Zhang, X., Eremin, S. A., Wen, K., Yu, X., Li, C., Ke, Y., … Wang, Z. (2017). Fluorescence Polarization Immunoassay Based
715 on a New Monoclonal Antibody for the Detection of the Zearalenone Class of Mycotoxins in Maize. Journal of Agricultural and
716 Food Chemistry, 65(10), 2240–2247. doi:10.1021/acs.jafc.6b05614
717 71. Tothill, I. (2011). Biosensors and nanomaterials and their application for mycotoxin determination. World Mycotoxin Journal,
718 4(4), 361–374. doi:10.3920/wmj2011.1318
719 72. Eivazzadeh-Keihan, R., Pashazadeh, P., Hejazi, M., de la Guardia, M., & Mokhtarzadeh, A. (2017). Recent advances in
720 Nanomaterial-mediated Bio and immune sensors for detection of aflatoxin in food products. TrAC Trends in Analytical
721 Chemistry, 87, 112–128. doi:10.1016/j.trac.2016.12.003
722 73. Ahlberg, S. H., Joutsjoki, V., & Korhonen, H. J. (2015). Potential of lactic acid bacteria in aflatoxin risk mitigation. International
723 Journal of Food Microbiology, 207, 87–102. doi:10.1016/j.ijfoodmicro.2015.04.042
724 74. Elsanhoty, R. M., Ramadan, M. F., El-Gohery, S. S., Abol-Ela, M. F., & Azeke, M. A. (2013). Ability of selected
725 microorganisms for removing aflatoxins in vitro and fate of aflatoxins in contaminated wheat during baladi bread baking. Food
726 Control, 33(1), 287–292. doi:10.1016/j.foodcont.2013.03.002
727 75. Śliżewska, K., & Smulikowska, S. (2011). Detoxification of aflatoxin B1 and change in microflora pattern by probiotic in vitro
728 fermentation of broiler feed. Journal of Animal and Feed Sciences 20(2), 300–309.
729 76. Raksha Rao, K., Vipin, A. V., Hariprasad, P., Anu Appaiah, K. A., & Venkateswaran, G. (2017). Biological detoxification of
730 Aflatoxin B 1 by Bacillus licheniformis CFR1. Food Control, 71, 234–241. doi:10.1016/j.foodcont.2016.06.040
731 77. Wang, J.Q., Yang, F., Yang, P.L., Liu, J., & Lv, Z.H. (2018). Microbial reduction of zearalenone by a new isolated
732 Lysinibacillus sp. ZJ-2016-1. World Mycotoxin Journal, 11(4), 571–578. doi.org/10.3920/WMJ2017.2264
733 78. Lei, Y. P., Zhao, L. H., Ma, Q. G., Zhang, J. Y., Zhou, T., Gao, C. Q., & Ji, C. (2014). Degradation of zearalenone in swine feed
734 and feed ingredients by Bacillus subtilis ANSB01G. World Mycotoxin Journal, 7(2), 143–151. doi:10.3920/wmj2013.1623
735 79. Sangare, L., Zhao, Y., Folly, Y., Chang, J., Li, J., Selvaraj, J., … Liu, Y. (2014). Aflatoxin B1 Degradation by a Pseudomonas
736 Strain. Toxins, 6(10), 3028–3040. doi:10.3390/toxins6103028
737 80. Rodriguez, H., Reveron, I., Doria, F., Costantini, A., De Las Rivas, B., Muňoz, R., & Garcia-Moruno, E. (2011). Degradation of
738 Ochratoxin A by Brevibacterium Species. Journal of Agricultural and Food Chemistry, 59(19), 10755–10760.
739 doi:10.1021/jf203061p
740 81. Tan, H., Hu, Y., He, J., Wu, L., Liao, F., Luo, B., … Deng, J. (2014). Zearalenone degradation by two Pseudomonas strains from
741 soil. Mycotoxin Research, 30(4), 191–196. doi:10.1007/s12550-014-0199-x
742 82. He, J. W., Bondy, G. S., Zhou, T., Caldwell, D., Boland, G. J., & Scott, P. M. (2015). Toxicology of 3-epi-deoxynivalenol, a
743 deoxynivalenol-transformation product by Devosia mutans 17-2-E-8. Food and Chemical Toxicology, 84, 250–259.
744 doi:10.1016/j.fct.2015.09.003
745 83. Gao, X., Mu, P., Wen, J., Sun, Y., Chen, Q., & Deng, Y. (2018). Detoxification of trichothecene mycotoxins by a novel
746 bacterium, Eggerthella sp. DII-9. Food and Chemical Toxicology, 112, 310–319. doi:10.1016/j.fct.2017.12.066
747 84. Adebo, O. A., Njobeh, P. B., Gbashi, S., Nwinyi, O. C., & Mavumengwana, V. (2015). Review on microbial degradation of
748 aflatoxins. Critical Reviews in Food Science and Nutrition, 57(15), 3208–3217. doi:10.1080/10408398.2015.1106440
749 85. Saleemi, M. K., Ashraf, K., Gul, S. T., Naseem, M. N., Sajid, M. S., Mohsin, M., … Khan, A. (2020). Toxicopathological effects
750 of feeding aflatoxins B1 in broilers and its ameliosration with indigenous mycotoxin binder. Ecotoxicology and Environmental
751 Safety, 187, 109712. doi:10.1016/j.ecoenv.2019.109712
752 86. Yalcin, N. F., Avci, T., Isik, M. K., & Oguz, H. (2018). In vitro activity of toxin binders on aflatoxin B1 in poultry
753 gastrointestinal medium. Pak Vet J, 38(1): 61-65. doi:10.29261/pakvetj/2018.012
754 87. Khan, A., Aalim, M. M., Khan, M. Z., Saleemi, M. K., He, C., Khatoon, A., & Gul, S. T. (2017). Amelioration of
755 immunosuppressive effects of aflatoxin and ochratoxin A in White Leghorn layers with distillery yeast sludge. Toxin Reviews,
756 36(4), 275–281. doi:10.1080/15569543.2017.1303781
757 88. He, C., Fan, Y., Liu, G., & Zhang, H. (2008). Isolation and Identification of a Strain of Aspergillus Tubingensis With
758 Deoxynivalenol Biotransformation Capability. International Journal of Molecular Sciences, 9(12), 2366–2375.
759 doi:10.3390/ijms9122366
760 89. Vekiru, E., Hametner, C., Mitterbauer, R., Rechthaler, J., Adam, G., Schatzmayr, G., … Schuhmacher, R. (2010). Cleavage of
761 Zearalenone by Trichosporon mycotoxinivorans to a Novel Nonestrogenic Metabolite. Applied and Environmental Microbiology,
762 76(7), 2353–2359. doi:10.1128/aem.01438-09
763 90. Varga, J., Péteri, Z., Tábori, K., Téren, J., & Vágvölgyi, C. (2005). Degradation of ochratoxin A and other mycotoxins by
764 Rhizopus isolates. International Journal of Food Microbiology, 99(3), 321–328. doi:10.1016/j.ijfoodmicro.2004.10.034
765 91. Molnar, O., Schatzmayr, G., Fuchs, E., & Prillinger, H. (2004). Trichosporon mycotoxinivorans sp. nov., A New Yeast Species
766 Useful in Biological Detoxification of Various Mycotoxins. Systematic and Applied Microbiology, 27(6), 661–671.
767 doi:10.1078/0723202042369947
768 92. Peraica, M., Domijan, A., Jurjević, Ž. & Cvjetković, B. (2002). Prevention of Exposure to Mycotoxins from Food and Feed. Arh
769 Hig Rada Toksikol, 53(3), 229-237. https://hrcak.srce.hr/452
770 93. He, J., Zhou, T., Young, J. C., Boland, G. J., & Scott, P. M. (2010). Chemical and biological transformations for detoxification of
771 trichothecene mycotoxins in human and animal food chains: a review. Trends in Food Science & Technology, 21(2), 67–76.
772 doi:10.1016/j.tifs.2009.08.002
773 94. Calado, T., Venâncio, A., & Abrunhosa, L. (2014). Irradiation for Mold and Mycotoxin Control: A Review. Comprehensive
774 Reviews in Food Science and Food Safety, 13(5), 1049–1061. doi:10.1111/1541-4337.12095
775 95. Loi, M., Fanelli, F., Liuzzi, V., Logrieco, A., & Mulè, G. (2017). Mycotoxin Biotransformation by Native and Commercial
776 Enzymes: Present and Future Perspectives. Toxins, 9(4), 111. doi:10.3390/toxins9040111
777 96. Pankaj, S. K., Shi, H., & Keener, K. M. (2018). A review of novel physical and chemical decontamination technologies for
778 aflatoxin in food. Trends in Food Science & Technology, 71, 73–83. doi:10.1016/j.tifs.2017.11.007
779 97. Alberts, J. F., Gelderblom, W. C. A., Botha, A., & van Zyl, W. H. (2009). Degradation of aflatoxin B1 by fungal laccase
780 enzymes. International Journal of Food Microbiology, 135(1), 47–52. doi:10.1016/j.ijfoodmicro.2009.07.022
781 98. Heinl, S., Hartinger, D., Thamhesl, M., Vekiru, E., Krska, R., Schatzmayr, G., … Grabherr, R. (2010). Degradation of fumonisin
782 B1 by the consecutive action of two bacterial enzymes. Journal of Biotechnology, 145(2), 120–129.
783 doi:10.1016/j.jbiotec.2009.11.004
784 99. Zhao, L. H., Guan, S., Gao, X., Ma, Q. G., Lei, Y. P., Bai, X. M., & Ji, C. (2010). Preparation, purification and characteristics of
785 an aflatoxin degradation enzyme from Myxococcus fulvus ANSM068. Journal of Applied Microbiology, 110(1), 147–155.
786 doi:10.1111/j.1365-2672.2010.04867.x
787 100. Schatzmayr, G., Zehner, F., Täubel, M., Schatzmayr, D., Klimitsch, A., Loibner, A. P., & Binder, E. M. (2006). Microbiologicals
788 for deactivating mycotoxins. Molecular Nutrition & Food Research, 50(6), 543–551. doi:10.1002/mnfr.200500181
789 101. Hu, H. N., Jia, X., Wang, Y. P., & Liang Z. H. (2018). Removal of ochratoxin A by a carboxypeptidase and peptides present in
790 liquid cultures of Bacillus subtilis CW14. World Mycotoxin Journal 11(4), 559-570. doi.org/10.3920/WMJ2017.2296
791 102. Mgbeahuruike, A. C., Ejioffor, T. E., Christian, O. C., Shoyinka, V. C., Karlsson, M., & Nordkvist, E. (2018). Detoxification of
792 Aflatoxin-Contaminated Poultry Feeds by 3 Adsorbents, Bentonite, Activated Charcoal, and Fuller’s Earth. J. Appl. Poult. Res.
793 27, 461–471. doi:10.3382/japr/pfy054
794 103. Abd El-Hack, M. E., Samak, D. H., Noreldin, A. E., El-Naggar, K., & Abdo, M. (2018). Probiotics and plant-derived compounds
795 as eco-friendly agents to inhibit microbial toxins in poultry feed: a comprehensive review. Environmental Science and Pollution
796 Research. doi:10.1007/s11356-018-3197-2
797 104. Saeed, M., Yatao, X., Hassan, F., Arain, M., Abd El-Hack, M., Noreldin, A., & Sun, C. (2018). Influence of Graded Levels of l-
798 Theanine Dietary Supplementation on Growth Performance, Carcass Traits, Meat Quality, Organs Histomorphometry, Blood
799 Chemistry and Immune Response of Broiler Chickens. International Journal of Molecular Sciences, 19(2), 462.
800 doi:10.3390/ijms19020462
801 105. Abdelaziz, M. A., El-Faham, A. I., & Ali, N. G . (2015). Using Natural Feed Additives as Alternative Antimycotoxins in Broiler
802 Diets. Egyptian Poultry Science Journal, 35(1), 291–310.
803 106. Rangsaz, N., & Ahangaran, M. G. (2011). Evaluation of turmeric extract on performance indices impressed by induced
804 aflatoxicosis in broiler chickens. Toxicology and Industrial Health, 27(10), 956–960. doi:10.1177/0748233711401262
805 107. Stoev, S. D., Njobeh, P., Zarkov, I., Mircheva, T., Zapryanova, D., Denev, S., & Dimitrova, B. (2019). Selected herbal feed
806 additives showing protective effects against ochratoxin A toxicosis in broiler chicks. World Mycotoxin Journal, 12(3), 257-268.
807 doi.org/10.3920/WMJ2019.2432
808 108. Panda, P., & Mehta, A. (2013). Aflatoxin Detoxification Potential of Ocimum Tenuiflorum. Journal of Food Safety, 33(3), 265–
809 272. doi:10.1111/jfs.12048
810 109. Velazhahan, R., Vijayanandraj, S., Vijayasamundeeswari, A., Paranidharan, V., Samiyappan, R., Iwamoto, T., … Muthukrishnan,
811 S. (2010). Detoxification of aflatoxins by seed extracts of the medicinal plant, Trachyspermum ammi (L.) Sprague ex Turrill –
812 Structural analysis and biological toxicity of degradation product of aflatoxin G1. Food Control, 21(5), 719–725.
813 doi:10.1016/j.foodcont.2009.10.014
814 110. Elsamra, I. A., Shama, S. M., Hamza, A. S., Youssef, N. H., Youssef, M. S., & Alabd, S. M. (2012). Effect of some mould
815 inhibitors and herbal plants on mycotoxins production byAspergillus flavusandFusarium verticilloidesin vitro and in stored corn
816 grains. Archives Of Phytopathology And Plant Protection, 45(15), 1861–1878. doi:10.1080/03235408.2012.713799
817 111. Ponzilacqua, B., Rottinghaus, G. E., Landers, B. R., & Oliveira, C. A. F. (2019). Effects of medicinal herb and Brazilian
818 traditional plant extracts on in vitro mycotoxin decontamination. Food Control. doi:10.1016/j.foodcont.2019.01.009
819 112. Abd-Elsalam, K. A., Hashim, A. F., Alghuthaymi, M. A., & Said-Galiev, E. (2017). Nanobiotechnological strategies for
820 toxigenic fungi and mycotoxin control. Food Preservation, 337–364. doi:10.1016/b978-0-12-804303-5.00010-9
821 113. Gómez, J. V., Tarazona, A., Mateo, F., Jiménez, M., & Mateo, E. M. (2019). Potential impact of engineered silver nanoparticles
822 in the control of aflatoxins, ochratoxin A and the main aflatoxigenic and ochratoxigenic species affecting foods. Food Control,
823 101, 58–68. doi:10.1016/j.foodcont.2019.02.019
824 114. Hu, D., Yu, S., Yu, D., Liu, N., Tang, Y., Fan, Y., … Wu, A. (2019). Biogenic Trichoderma harzianum-derived selenium
825 nanoparticles with control functionalities originating from diverse recognition metabolites against phytopathogens and
826 mycotoxins. Food Control, 106, 106748. doi:10.1016/j.foodcont.2019.106748
827 115. Hassan, A. A., Howayda, M. E., & Mahmoud H. H. (2013). Effect of Zinc Oxide Nanoparticles on the Growth of some
828 Mycotoxigenic Mould. Studies in Chemical Process Technology (SCPT), 1(4), 66-74.
829 116. Luo, Y., Liu, X., & Li, J. (2018). Updating techniques on controlling mycotoxins - A review. Food Control, 89, 123–132.
830 doi:10.1016/j.foodcont.2018.01.016
831 117. Luo, Y., Zhou, Z., & Yue, T. (2017). Synthesis and characterization of nontoxic chitosan-coated Fe 3 O 4 particles for patulin
832 adsorption in a juice-pH simulation aqueous. Food Chemistry, 221, 317–323. doi:10.1016/j.foodchem.2016.09.008
833 118. Thipe, V. C., Keyster, M., & Katti, K. V. (2018). Sustainable Nanotechnology: Mycotoxin Detection and Protection.
834 Nanobiotechnology Applications in Plant Protection, 323–349. doi:10.1007/978-3-319-91161-8_12
835 119. Maragos, C. M., Sieve, K. K., & Busman, M. (2018). Development of antibodies for N-(1-deoxy-D-fructos-1-yl) fumonisin B1
836 and cross-reaction with modified fumonisins. World Mycotoxin Journal,11 (4): 493-502. doi.org/10.3920/WMJ2018.2308
837 120. Peschen, D., Li, H.-P., Fischer, R., Kreuzaler, F., & Liao, Y.-C. (2004). Fusion proteins comprising a Fusarium-specific antibody
838 linked to antifungal peptides protect plants against a fungal pathogen. Nature Biotechnology, 22(6), 732–738.
839 doi:10.1038/nbt970
840 121. Li, H.-P., Zhang, J.-B., Shi, R.-P., Huang, T., Fischer, R., & Liao, Y.-C. (2008). Engineering Fusarium Head Blight Resistance in
841 Wheat by Expression of a Fusion Protein Containing aFusarium-Specific Antibody and an Antifungal Peptide. Molecular Plant-
842 Microbe Interactions, 21(9), 1242–1248. doi:10.1094/mpmi-21-9-1242
843 122. Hu, Z.-Q., Li, H.-P., Zhang, J.-B., Glinka, E., & Liao, Y.-C. (2008). Antibody-mediated Prevention of Fusarium Mycotoxins in
844 the Field. International Journal of Molecular Sciences, 9(10), 1915–1926. doi:10.3390/ijms9101915
845 123. Temesgen, A., & Teshome, G. (2018). Major mycotoxins occurrence, prevention and control approaches. Biotechnology and
846 Molecular Biology Reviews, 12(1), 1–11. doi:10.5897/bmbr2018.0274
847 124. Tinoco, M., Dias, B. B., Dall’Astta, R. C., Pamphile, J. A., & Aragão, F. J. (2010). In vivo trans-specific gene silencing in fungal
848 cells by in planta expression of a double-stranded RNA. BMC Biology, 8(1), 27. doi:10.1186/1741-7007-8-27
849 125. Wang, M., Weiberg, A., Lin, F.-M., Thomma, B. P. H. J., Huang, H.-D., & Jin, H. (2016). Bidirectional cross-kingdom RNAi
850 and fungal uptake of external RNAs confer plant protection. Nature Plants, 2(10). doi:10.1038/nplants.2016.151
851 126. Arias, R. S., Dang, P. M., & Sobolev, V. S. (2015). RNAi-mediated Control of Aflatoxins in Peanut: Method to Analyze
852 Mycotoxin Production and Transgene Expression in the Peanut/Aspergillus Pathosystem. Journal of Visualized Experiments,
853 (106). doi:10.3791/53398
854 127. Campo, S., Peris-Peris, C., Siré, C., Moreno, A. B., Donaire, L., Zytnicki, M., … San Segundo, B. (2013). Identification of a
855 novel microRNA (miRNA) from rice that targets an alternatively spliced transcript of theNramp6(Natural resistance-associated
856 macrophage protein 6) gene involved in pathogen resistance. New Phytologist, 199(1), 212–227. doi:10.1111/nph.12292
857 128. Puchta, H. (2017). Applying CRISPR/Cas for genome engineering in plants: the best is yet to come. Current Opinion in Plant
858 Biology, 36, 1–8. doi:10.1016/j.pbi.2016.11.011
859 129. Bakan, B., Melcion, D., Richard-Molard, D., & Cahagnier, B. (2002). Fungal Growth and Fusarium Mycotoxin Content in
860 Isogenic Traditional Maize and Genetically Modified Maize Grown in France and Spain. Journal of Agricultural and Food
861 Chemistry, 50(4), 728–731. doi:10.1021/jf0108258
862 130. Wall, R. J., Powell, A. M., Paape, M. J., Kerr, D. E., Bannerman, D. D., Pursel, V. G., … Hawk, H. W. (2005). Genetically
863 enhanced cows resist intramammary Staphylococcus aureus infection. Nature Biotechnology, 23(4), 445–451.
864 doi:10.1038/nbt1078
865 131. Lillico, S. G., Proudfoot, C., King, T. J., Tan, W., Zhang, L., Mardjuki, R., … Whitelaw, C. B. A. (2016). Mammalian
866 interspecies substitution of immune modulatory alleles by genome editing. Scientific Reports, 6(1). doi:10.1038/srep21645
867 132. Forabosco, F., Löhmus, M., Rydhmer, L., & Sundström, L. F. (2013). Genetically modified farm animals and fish in agriculture:
868 A review. Livestock Science, 153(1-3), 1–9. doi:10.1016/j.livsci.2013.01.002
869 133. Plotan, M., Devlin, R., Porter, J., Benchikh, M. E. O., Rodríguez, M. L., McConnell, R. I., & FitzGerald, S. P. (2016). The Use of
870 Biochip Array Technology for Rapid Multimycotoxin Screening. Journal of AOAC International, 99(4), 878–889.
871 doi:10.5740/jaoacint.16-0115
872 134. He, J., Zhou, T., Young, J. C., Boland, G. J., & Scott, P. M. (2010). Chemical and biological transformations for detoxification of
873 trichothecene mycotoxins in human and animal food chains: a review. Trends in Food Science & Technology, 21(2), 67–76.
874 doi:10.1016/j.tifs.2009.08.002