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FMN was reported in feed and some cereal grains consumed in Malaysia. Since some food commodities are more susceptible than others to fungal growth and ...
A Review on Mycotoxins in Food and Feed: Malaysia Case Study L. Afsah-Hejri, S. Jinap, P. Hajeb, S. Radu, and Sh. Shakibazadeh

Abstract: Fungi are distributed worldwide and can be found in various foods and feedstuffs from almost every part of the world. Mycotoxins are secondary metabolites produced by some fungal species and may impose food safety risks to human health. Among all mycotoxins, aflatoxins (AFs), ochratoxin A (OTA), trichothecenes, deoxynivalenol (DON and T-2 toxin), zearalenone (ZEN), and fumonisins (FMN) have received much attention due to high frequency and severe health effects in humans and animals. Malaysia has heavy rainfall throughout the year, high temperatures (28 to 31 ◦ C), and high relative humidity (70% to 80% during wet seasons). Stored crops under such conditions can easily be contaminated by mycotoxin-producing fungi. The most important mycotoxins in Malaysian foods are AFs, OTA, DON, ZEN, and FMN that can be found in peanuts, cereal grains, cocoa beans, and spices. AFs have been reported to occur in several cereal grains, feeds, nuts, and nut products consumed in Malaysia. Spices, oilseeds, milk, eggs, and herbal medicines have been reported to be contaminated with AFs (lower than the Malaysian acceptable level of 35 ng/g for total AFs). OTA, a possible human carcinogen, was reported in cereal grains, nuts, and spices in Malaysian market. ZEN was detected in Malaysian rice, oat, barley, maize meal, and wheat at different levels. DON contamination, although at low levels, was reported in rice, maize, barley, oat, wheat, and wheat-based products in Malaysia. FMN was reported in feed and some cereal grains consumed in Malaysia. Since some food commodities are more susceptible than others to fungal growth and mycotoxin contamination, more stringent prevention and control methods are required. Keywords: aflatoxins, ochratoxin A, trichothecenes, deoxynivalenol, zearalenone, fumonisins, cereals, nuts, spices

Introduction Mycotoxins are secondary metabolites produced by some fungal species. Fungi are the eukaryotic and multinucleus organisms that usually show filamentous growth (Hawksworth and others 1996). Fungi are distributed worldwide and can be found in various food and feedstuffs from almost every part of the world (PfohlLeszkowicz and others 2002). Fungi and fungal spores are able to colonize and penetrate deep into the matrices of agricultural crops and produce mycotoxins during preharvest and postharvest practices, and processing and storage stages (Bhat and others 2010). More than 300 different mycotoxins have been detected so far (Erber and Binder 2004). Mycotoxins are synthesized under suitable biological, chemical, and physiological conditions. Toxin production is influenced by some ecological and environmental factors such as temperature, type of substrate, moisture content, relative humidity, water activity (aw ), occurrence with other fungi, physical damage by insects, use of fungicides, and storage condi-

MS 20130412 Submitted 3/23/2013, Accepted 6/17/2013. Authors Afsah-Hejri, Jinap, Hajeb, and Radu are with Food Safety Research Centre (FOSREC), Faculty of Food Science and Technology, Univ. Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia. Author Shakibazadeh is with Dept. of Aquaculture, Faculty of Agriculture, Univ. Putra Malaysia, 43400, UPM Serdang, Selangor, Malaysia. Direct inquiries to author Hajeb (E-mail: [email protected]).

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doi: 10.1111/1541-4337.12029

tions (Z¨ollner and Mayer-Helm 2006). Several other factors such as poor harvesting practices, improper processing, packaging, drying techniques, and transport activities influence fungal growth and increase the risk of mycotoxin production (Bhat and others 2010). Climate changes seem to be another important factor affecting mycotoxin contamination of foods and feedstuffs (Paterson and Lima 2010). Depending on the geographical and climate conditions, different fungal species can invade foods and feedstuffs. Aspergillus, Penicillium, and Fusarium species are the most important mycotoxin producers. Penicillium and Aspergillus species can grow at higher temperature and lower aw than Fusarium. Fusarium species grow well at higher aw and lower temperature (Bhat and others 2010). Aspergillus species can be found on nuts, cereals, palm kernels, cocoa, and coffee beans (Kozakiewicz 1996). Depending on the structure and biological origin, mycotoxins can be classified into 4 categories (polycetoacids, terpenes, cyclopeptides, and nitrogenous metabolites) (Bhat and others 2010). Among all mycotoxins, aflatoxins (AFs), ochratoxin A (OTA), trichothecenes (deoxynivalenol (DON) and T-2 toxin), zearalenone (ZEN), and fumonisins (FMN) have received much attention due to high frequency and severe health effects in humans and animals (Bhat and others 2010). AFs, DON, and ergot alkaloids are usually produced at preharvest stages, while FMN and OTA are mainly produced during postharvest activities (Bhat and others 2010). Naturally contaminated crops may contain multiple mycotoxins resulting

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A review on mycotoxins in food and feed . . . cultural crops may occur in 2 ways; the first is when fungi grow as pathogen on a plant and the second one is when fungi grow saprophytically on stored crops (Glenn 2007). It should be mentioned that observation of fungi does not necessarily mean presence of mycotoxins, and not all fungal growth results in mycotoxin production (Binder and others 2007). Fungal growth and toxin production depends on environmental factors (such as warm temperatures and high humidity). Therefore, agricultural products in subtropical and tropical regions are more susceptible to fungal infestation, and consequently, mycotoxin contamination. If subtropical and tropical countries have poorly developed infrastructures (such as processing facilities, transportation, storage, and skilled human resources), more mycotoxin contamination may be observed (Miller and others 1993). Based on the moisture requirements, mycotoxin producers can be divided into 3 groups: field fungi, storage fungi, and advanced decay fungi. The field fungi mycotoxin producers require a grain moisture content of 22% to 25%, while storage mycotoxin producers usually grow in grain with a moisture content of 13% to 18% (equal to 70% to 90% relative humidity), and advanced decay fungi require over 18% moisture (Agag 2004; Bankole and Adebanjo 2004). Fardiaz (1995) studied susceptibility of some foodstuffs (cereal grains, rice, soybean, maize, and peanuts) to aflatoxin contamination and found peanuts and maize to be the most susceptible commodities. As peanuts grow in the soil, various fungi contaminate peanut shell, testa, and seed. Any mechanical damage during harvest, drying, and storage increases the chance of fungal contamination and mycotoxin production. Manual harvesting, sorting wet peanuts, and storage under improper conditions favor fungal growth. Besides, aflatoxin producers are more frequently found in warm areas (Fardiaz 1995). Maize is usually contaminated with FMN and ZEN. AFs, OTA, DON, and ergot alkaloids are commonly observed in cereal grains (Puntari and others 2001; Lewis and others 2005; Wu 2006; Fu and others 2008; Hong and Nurim 2010; Reddy and Salleh 2011; Rodrigues and Chin 2012). In developed countries, severe governmental regulations together with implementation of modern food preservation and handling techniques resulted in fewer mycotoxicosis outbreaks compared to developing countries (Bhat and others 2010). Severity of mycotoxicosis depends on such factors as type and dose of mycotoxin, extent of exposure, health condition, gender, and age of the individual (Bankole and Adebanjo 2004). Depending Mycotoxins in Foods and Their Risk to Human Health on these factors, mycotoxin-contaminated foodstuffs can cause Mycotoxin contamination of foodstuffs is a worldwide problem chronic and/or acute health problems in humans and animals. and a major health threat for humans and animals that cause significant economic losses in both developing and developed countries. Besides, mycotoxin contaminations of agricultural crops pose sig- Mycotoxin Contamination of Feedstuffs nificant economic losses to both crop producer and handlers who Mycotoxin contamination of feedstuffs can impose health hazhave to give market discounts for the contaminated products. In ards to human as mycotoxins appear in animal’s tissue and body cases of severely contaminated crops, they have to dispose of the fluids. Monogastric farm animals (such as poultry and swine) are product. Other economic losses related to mycotoxin contamina- more susceptible to AFs due to the following 2 reasons: first, cetion of foodstuffs are loss of business and product recall (Herrman reals are a large part of their diet and, 2nd, they lack the ruminal and others 2002). reservoir of a multitude of microorganisms. Ruminants seem to Cereals (wheat, rice, maize, and sorghum), oilseeds (sunflower, be less susceptible to mycotoxins rather than other animals as their peanut, cottonseed, and soybean), spices (black pepper, chillies, rumen flora has the ability to convert some mycotoxins into less turmeric, coriander, and ginger), tree nuts (pistachio, almond, carcinogen metabolites or biologically inactive compounds (for excoconut, and walnut) are the most important agricultural com- ample, AFB1 is converted to its less carcinogen metabolite AFM1 modities that can be contaminated with mycotoxins. Milk (animal in a ruminant’s body) (Fink-Gremmels 2008). Biotransformation and human), cheese, and butter can be a source of mycotoxin- of AFB1 in hens’ liver results in some toxic hydroxylated metabocontamination if mycotoxin contaminated food or feed is con- lites that are transferable to eggs (Zaghini and others 2005; Pandey sumed (Bhat and others 2010). Mycotoxin contamination of agri- and Chauhan 2007; Aly and Anwer 2009; Herzallah 2009).

in more severe effects. Multitoxin occurrence or co-occurrence of mycotoxins results in synergistic effects of mycotoxins, especially in acute toxicities in animals (such as AFs with DON, and T2 toxin, OTA with FMN, and FMN with DON) (Binder and others 2007). Aspergillus species can produce different types of mycotoxins such as AFs, OTA, cyclopiazonic acid, patulin, citrinin, and ergot alkaloids (Li and others 2003; Flajs and Peraica 2009; Bhat and others 2010). Aspergillus toxins can be classified into 3 groups: carcinogens (AFs), nephrotoxins (OTA), and neurotoxins (territrems) (Ling and others 1979, 1984; Kozakiewicz 1996). Territrems, toxic metabolites produced by Aspergillus terreus, show blue fluorescence under UV light. Territrem A, territrem B, and territrem C can be found in rice and induce tremors and convulsion in mice (Ling and others 1979, 1984). Penicillium species produce AFs, OTA, cyclopiazonic acid, patulin, citrinin, and ergot alkaloids (Goto and others 1996; Li and others 2003; Flajs and Peraica 2009; Bhat and others 2010). FMN and ZEN are produced by some Fusarium species (Minervini and others 2005; Glenn 2007; Cozzini and Dellafiora 2012), while trichothecenes (DON, T-2 toxin, diacetoxyscirpenol, and nivalenol) are produced by several fungal genera such as Fusarium, Trichoderma, Myrothecium, Stachybotrys, Trichotecium, and Phomopsis (Kumar and others 2008). Alternaria toxins are secondary metabolites of Alternaria spp. (Ostry 2008), and Claviceps purpurea is the main producer for ergot alkaloids (Krska and Crews 2008). Mycotoxins may be inhaled, ingested, or absorbed through the skin. No matter how mycotoxins are entered, they can cause sickness, lower performance, or death in both animals and humans (Bankole and Adebanjo 2004). Mycotoxicosis is the consequence of ingesting mycotoxin-contaminated food or feed by higher animals (Binder and others 2007). Sometimes, mycotoxicosis is caused through indirect ways such as consumption of products from animals (milk or meat) exposed to contaminated feed (Bankole and Adebanjo 2004). Consumption of mycotoxin-contaminated food or feed results in acute or chronic consequences such as carcinogenic, teratogenic, immunesuppressive, or estrogenic effects (Binder and others 2007). Mycotoxins target the liver, kidney, nervous system, and immune system and common symptoms of mycotoxicosis in human are diarrhea, vomiting, and gastrointestinal problems (Bhat and others 2010).

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A review on mycotoxins in food and feed . . . Some feedstuffs such as soybean products, corn gluten, peanut cakes, sunflower seeds, palm kernels, and cotton seeds can be contaminated with AFs. Some preserved feed for dairy cows (example, hay, silage, and straw) easily gets contaminated by mycotoxigenic fungi during preharvest or postharvest activities and drying stages (Fink-Gremmels 2008; Bhat and others 2010). Use of mycotoxincontaminated feed reduces feed intake and less nutrient absorption in the digestive tract of animals and causes decrease in body weight gain, reduction in animal productivity, damage to vital organs, increased incidence of disease due to immunosuppression, interference with reproductive capacity, and death in severe cases (Herrman and others 2002; Fink-Gremmels and Malekinejad 2007; Morgavi and Riley 2007; Bhat and others 2010).

International and National Regulations for Mycotoxins To date, 100 countries have established regulations to protect consumers from the harmful effects of mycotoxins. Depending on the country, human foods are allowed a total of 4 to 30 ng/g of AFs. The maximum total AF residue limit in human food in the U.S.A. is 20 ng/g, and 4 ng/g is the maximum amount of AFs allowed in food in the EU, which has the strictest standards worldwide (EC 2006; Fellinger 2006; Wu 2006; Zain 2010). According to the European Committee Regulations, the AF maximum permitted level in peanuts, dried fruits, and cereals (for direct human consumption or as an ingredient in foods) is set as 5 ppb for AFB1 and 10 ppb for total AFs (Moss 2002). Due to the harmful effects of OTA and increasing knowledge of health hazards, many countries have established a limit for OTA in food and feed. At the 37th, 44th, and 56th meetings of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), a provisional tolerable weekly intake (PTWI) of 100 ng/kg BW for OTA was established (JECFA 2001). In a recent proposal from the European Union (EU), which has been effective since October 1, 2006, the maximum tolerated limit for OTA was reduced to below 5 ng/kg BW/d (EC 2006; Fellinger 2006; Wu 2006; Zain 2010). According to the European Commission (Regulation 1881/2006), the maximum contamination level of OTA in processed cereal-based foods and baby foods for infants and young children and dietary foods for special medical purposes intended specifically for infants is 0.5 ng/g, while for unprocessed cereals and coffee, it is 5 ng/g (EC 2006). Based on the FAO’s worldwide regulations for mycotoxins in food/feedstuffs, several countries have set the maximum residual limit for ZEN in maize and cereal at less than 100 ng/g (FAO 2004). According to the JECFA, the maximum tolerable daily intake for ZEN is 0.5 μg/kg BW (JECFA 2000), while tolerance levels ZEN in food in Europe are 60 to 200 ng/g (El-Nezami and others 2002). According to European Commission Regulation 2007, the maximum residue limit for ZEN in unprocessed cereals, unprocessed maize, cereal for direct consumption, maize for direct consumption, and processed maize/cereal-based foods is 100, 350, 75, 100, and 20 ng/g, respectively (European Commission 2007) and the maximum level of ZEN in wheat bran (used as ingredient in high fiber breakfast cereals) should not exceed 125 μg/kg (European Commission 2000). According to the Joint FAO/WHO Expert Committee on Food and Additives, the permitted level of T-2 toxin is 1 μg/kg BW (JECFA 2001). In most food products, the maximum tolerated level for DON is in the range of 500 to 1000 μg/kg (Van Egmond 2002; Bhat and others 2010) but the European Commission Regulation of 2007 has set the maximum permitted level for DON in cereal-based foods for infants and children, as well as cere C 2013 Institute of Food Technologists®

als intended for direct human use and finished wheat products for human consumption at 200, 750, and 1000 ng/g, respectively (European Commission 2007). Some countries (Russia and France) have set a maximum permitted level for T-2 toxin in malt and unprocessed cereals at 100 ng/g. In Slovakia, the maximum permitted level for T-2 toxin in cereal-based foods for children is set at 0.5 ng/g (FAO 2004). In other European countries, the maximum permitted level for DON in feed is 400 to 5000 ng/g. According to the European Commission regulation, maximum residual limits of FB1and FB2 in cereals, maize for direct consumption, maize-based breakfast cereals, and maize-based foods/baby foods are 4000, 1000, 800, and 200 ng/g, respectively (European Commission 2007). To avoid apoptosis and sphingolipid metabolism disruption related to the potential carcinogenicity of FMN, daily intake of liver > muscle > fat. Renal and biliary routes are involved in of OTA. OTA elimination routs vary with the following factors: route of administration and OTA dose. Kidney is the main route of excretion in humans and monkeys (Pfohl-Leszkowicz and Manderville 2007). There are 2 known metabolic pathways for OTA. According to Ringot and others (2006), the major metabolites include hydroxylated derivatives (4(R)-OHOTA, 4(S)-OHOTA, and OTAalpha (OTa) (lacking the phenylalanine moiety). Almost 10 different OTA derivatives were identified in cell culture and pig kidney microsomes (Ringot and others 2006; Pfohl-Leszkowicz and Manderville 2007). According to Marin-Kuan and others (2008), oxidative stress induced by OTA leads to DNA damage and mutations. Production of oxygen radicals is directly increased by OTA or is an indirect consequence of the inhibition of Nrf2-regulated antioxidant gene expression (Marin-Kuan and others 2008). In addition, OTA triggers a set of complex biological effects, which are related to cell proliferation and tumor development in renal tissue. Depending on the individual cell-specific susceptibility and intracellular OTA concentration, toxicity, apoptosis, or tumor development may occur. OTA’s effect on DNA is the result of blocking repair mechanisms and the genotoxicity of OTA is due to its ability to promote DNA adducts formation (Pfohl-Leszkowicz and Manderville 2007). In addition, OTA disrupts blood coagulation

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A review on mycotoxins in food and feed . . . and glucose metabolism, resulting in toxic effects in some organs the estrogenic activity of ZEN, farm animals fed with ZENcontaminated feed show alterations in the reproductive tract, de(Gupta and others 2007). crease in fertility, increase in number of fetal resorptions and implementation failure, and reduced litter size (Morgavi and Riley ZEN ZEN, (3,4,5,6,9,10-hexahydro-14,16-dihydroxy-3-methyl- 2007). The alterations in reproductive tract are permanent. Strong 1H-2 benzoxacyclotetradecin-1,7(8H)-dione, is a macrocyclic hyperestrogenic responses can be observed in animals susceptiß-resorcylic acid lactone (Diekman and Green 1992; European ble to ZEN (such as swine) (Coulombe 1993). Hyperestrogenism Commission 2000; JECFA 2000; Minervini and others 2005; in swine has been related to consumption of moldy grain (BenBhat and others 2010; Cozzini and Dellafiora 2012). ZEN is a nett and Klich 2009). Among animals, pigs are the most sensinonsteroidal estrogen or mycoestrogen and was previously known tive and poultry are the least affected by ZEN (Bhat and othas F-2 toxin (Morgavi and Riley 2007; Zinedine and others ers 2010). In pigs, ZEN poisoning is usually associated with 2007b). ZEN is biosynthesized through a polyketide pathway by feminizing syndromes or hyperestrogenic activity and causes urisome Fusarium species (Huffman and others 2010). According nary/genital problems (Danicke and others 2005). According to to the Intl. Agency for Research on Cancer (IARC), ZEN is the Joint FAO/WHO Expert Committee, the safety of ZEN is classified as Group 3 (not carcinogen to humans). Field fungi evaluated on the basis of the dose that has no hormonal effect in such as Fusarium graminearum (Gibberella zeae) (formerly named F. pigs (JECFA 2000). According to Wood (1992), consumption of low-dosed ZENroseum) is the main producer of ZEN. F. culmorum, F. verticillioides, contaminated feedstuffs by dairy cows does not pose any health F. cerealis, F. Semitectum, F. crookwellense, F. pseudograminearum, and F.equiseti are other ZEN producers (European Commission 2000; hazards to humans (Wood 1992). The rumen flora can convert Glenn 2007). Some derivatives of ZEN (such as α-zearalenol, ZEN into its hydroxy-metabolite α-zearalenol (almost 90%) and α-zearalanol, β-zearalanol, β-zearalenol, and zearalanone) β-zearalenol (Fink-Gremmels 2008). As reported by Takahashihave been found in Fusarium-infected corn stems in the field Ando and others (2002), lactonohydrolases produced by microflora in the large intestines of monogastric mammalian is able to con(Minervini and others 2005). vert ZEN to its nonestrogenic compound. Compared to ZEN, α-zearalenol has higher estrogenic potency, but as its rate of abOccurrence of ZEN Fusarium species are able to grow in moist and cool conditions sorption is lower, it affects dairy cattle less than ZEN (Finkand invade crops both in preharvest, postharvest, and under poor Gremmels 2008). Cytotoxic effects of α and β Zearalenols are storage conditions, but toxin production usually occurs at posthar- due to inhibition of DNA and protein syntheses and inducing vest activities and storage (European Commission 2000; Zinedine oxidative damage (Othmen and others 2008). In cases that lactating cows are fed with an oral dose of 6000 and others 2007b). Crops such as corn, maize, wheat, barley, rice, oats, millet, and sorghum can easily be contaminated by ZEN mg zearalenone (equivalent to 12 mg/kg BW), 6.6 μg/L β(European Commission 2000; JECFA 2000; Zinedine and others zearalenol, 4 μg/L α-zearalenol, and 6.1 μg/L zearalenone can 2007b). ZEN has been reported in cereal products (for example be detected in the milk (JECFA 2000). ZEN was found in 55.1% malt, beer, soybeans, and flour), corn silage, corn by-products, and and 22.4% of the endometrial tissues from women suffering from soya meal (Schollenberger and others 2007; Zinedine and others endometrial adenocarcinoma and endometrial hyperplasia, respec2007b). ZEN has also been reported in eggs (Sypecka and others tively (Tomaszewski and others 1998). Zearalanol and ZEN were 2004). Very low levels of ZEN and its metabolites (usually below detected in blood plasma of girls aged 6 mo to 8 y old sufferthe limit of quantification) might be found in milk (Seeling and ing from premature thelarche in Puerto Rico between 1978 and others 2005). ZEN is a heat-stable mycotoxin, but under alkaline 1981 (Saenz de Rodriguez and others 1985). Following oral adconditions, a temperature higher than 150 ◦ C can degrade the ministration, ZEN is rapidly absorbed by body and high level toxin (European Commission 2000). Due to high consumption of toxin can be measured in serum. It was reported that oral rate of cereal-based food products, children are more affected by bioavailability of ZEN can reach to 80% to 85% of the ingested dose. ZEN is widely distributed and slowly eliminated from body ZEN-contaminated foods (Bhat and others 2010). tissues (Kuiper-Goodman and others 1987; Fink-Gremmels and Malekinejad 2007). Kuiper-Goodman and others (1987) reported Adverse effects and toxicity of ZEN ZEN can cause infertility, abortion, reproduction problems that 67% of total oral dose of ZEN was excreted within 48 h (especially in swine), and is associated with cervical cancer (Bhat- and 45% and 22% of the oral was recovered in urine and faeces, nagar and others 2002; El-Nezami and others 2002). Ingestion of respectively. The rate of renal excretion was higher in rabbits and contaminated feed results in interference with the exocrine and humans. ZEN can be deposited in body tissues and carry over into endocrine systems. Like other environmental estrogens, ZEN has milk. As reported by Prelusky and others (1990), ZEN and its mathe potential to disrupt sex steroid hormone functions (Bennett jor metabolites (α and β Zearalenols) were detected in plasma and and Klich 2009; Bhat and others 2010). ZEN and its metabolites milk of lactating cows. ZEN is reduced to its major metabolites (α and β Zearalenols) bind to estrogen receptors and activate gene transcription. Besides, they interfere with the regular activity of the endocrine glands by 3-α and 3-β-hydroxysteroid dehydrogenase as catalysts (Olsen (Malekinejad and others 2005; Fink-Gremmels and Malekinejad and Kiessling 1983; Othmen and others 2008). This biotransformation mostly occurs in liver, but gut microflora and intestinal 2007). In several incidences, ZEN has been associated with some pu- mucosa were reported to be able to metabolize ZEN (Biehl and bertal changes (Kuiper-Goodman and others 1987). Freni-Titulaer others 1993; Kollarczik and others 1994; Danicke and others 2001, and others (1986) observed a significant correlation between 2002). Due to the steroid metabolism in target organs, conversion the pubertal changes and consumption of ZEN-contaminated of ZEN can be observed (Malekinejad and others 2006). ZEN soya-based products and meat from animals fed with ZEN- has great affinity to uterine and oviduct estrogen receptors in pig, contaminated feed (Freni-Titulaer and others 1986). Due to rat, and chicken (Fitzpatrick and others 1989). In most animal 636 Comprehensive Reviews in Food Science and Food Safety r Vol. 12, 2013

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A review on mycotoxins in food and feed . . . species (except rabbits), ZEN and its metabolites are excreted in the bile in rabbits urine is the main route (Kuiper-Goodmanand others 1987). In the elimination process, the alcoholic metabolites (α and β Zearalenol) are excreted as free compounds and glucuronide conjugates through faeces and urine (Danicke and others 2001; Othmen and others 2008). Kuiper-Goodman and others (1987), reported low acute oral toxicity of ZEN (with LD50 values 4000 mg/kg b.w.) for rodents. The suggested tolerable daily intake of ZEN is estimated to be 0.05 μg/kg BW/d (Kuiper-Goodman and others 1987).

Trichothecenes The causative agents for feed refusal syndrome in the 1930s were probably trichothecenes (Morgavi and Riley 2007). In 1949, the first member of the trichothecenes class was isolated from Trichothecium roseum and named trichothecin (Glenn 2007). The very large family of trichothecenes consists of several chemically related toxins produced by different species of Fusarium, Trichoderma, Myrotecium, Verticimonosporium, Trichotecium, Cephalosporium, Stachybotrys, and Cylindrocarpon (Glenn 2007; Bhat and others 2010). Trichothecenes cover almost 190 different structures all having in common a tetracyclic sesquiterpenoid 12,13-epoxytrichothec-9ene ring system (Ueno 1983; Desjardins and others 1993; Z¨ollner and Mayer-Helm 2006). Based on some structural features, trichothecenes are divided into 4 main groups. Group A (T-2 toxin, HT-2 toxin, neosolaniol, and diacetoxyscirpenol) are without a carbonyl group at position C-8 and have an oxygen function at C-8. Group B (DON and its derivatives, nivalenol, 3-acetyldeoxynivalenol, fusarenon-X, and 15-acetyldeoxynivalenol) have a carbonyl group at C-8. Group C and D have a second epoxy group and a macrocyclic structure, respectively (Ueno 1983; Berthiller and others 2005). Group A trichothecenes are the most toxic (Mirocha and others 2003; Bhat and others 2010). Trichothecenes of concern produced by Fusarium spp. are deoxynivalenol (DON), T-2 toxin, diacetoxyscirpenol, and nivalenol (Glenn 2007). Toxicity of T-2 toxin is 10 times more than DON in mammals (Ueno 1983). DON, the most prevalent toxin in this group, belongs to type B trichothecenes that are more phytotoxic (Mirocha and others 2003; Foroud and Eudes 2009). Trichothecenes are relatively insoluble in water, nonvolatile, and have low molecular weight. All members have a trichothecene ring in their chemical structure and are stable under different environmental conditions (Wannemacher and others 1997). Trichothecenes are produced by several fungal genus such as Fusarium, Trichoderma, Myrothecium, Stachybotrys, Trichotecium, and Phomopsis (Kumar and others 2008). DON was first reported in Japan and named “Rd-toxin.” The same compound was then isolated from contaminated corn used as feed for pigs with emesis and named “vomitoxin” (Morooka and others 1972; Morgavi and Riley 2007). DON has other names, including amphetamine deoxynivalenol and alpha methyl phenethylamine (Herrman and others 2002; Bhat and others 2010). DON is highly stable and can survive food processing procedures such as milling and powdering. In corn and wheat, DON is mainly produced by F. graminearum (Bhat and others 2010).

Occurrence of trichothecenes Fusarium graminearum and Fusarium culmorum produce DON that is the most prevalent trichothecene in food/feedstuffs and cause problems also in temperate zones of the world. Fusarium pseudograminearum, F. graminearum, and F. culmorum are responsible for the production of DON grain (Glenn 2007). The main sources for tri C 2013 Institute of Food Technologists®

chothecene contamination are grains such as corn, barley, wheat, and oats (Z¨ollner and Mayer-Helm 2006). Trichothecenes were detected in cereal products and milk (Sørensen and Elbaek 2005; Spanjer and others 2008). DON and its metabolite were reported in eggs (Sypecka and others 2004). Fusarium-contaminated wheat, millet, and barley were responsible for the syndrome named alimentary toxic aleukia in Siberia, Russia, between 1942 and 1947 (Wannemacher and others 1997). The “red mold disease” of barley and wheat in Japan was attributed to Fusarium spp. Deoxynivalenol and nivalenol were isolated from moldy grains (Wannemacher and others 1997).

Adverse effects and toxicity of trichothecenes Trichothecenes have been strongly associated with fatal and chronic toxicoses both in humans and animals. Exposure to trichothecenes results in delayed growth in eukaryotes. Humans, mammals, fish, birds, invertebrates, and plants can be affected by trichothecenes (Wannemacher and others 1997). Plant regeneration and mammals reproduction is affected by trichothecenes (Rocha and others 2005). Trichothecenes are phytotoxic to parsnip, wheat, and maize (Desjardins 2006; Pestka 2007). Fusarium spp. cause scab in wheat and root and stalk rots in corn and sorghum. At the flowering stage, plants are more susceptible to fungal infection. Warm and moist conditions in the field favor Fusarium invasion of grain crops and formation of DON or T-2 toxin (Herrman and others 2002). Some of the trichothecene mycotoxicoses include swine feed refusal as observed in the U.S.A., akakabi-byo or red mold disease in Japan, and alimentary toxic aleukia in Central Asia and Russia (Desjardins and Proctor 2007). Trichothecenes have an amphipathic nature that allows them to cross the cell membrane and interact with endoplasmic reticulum (Yang and others 2000), chloroplast (Bushnell and others 2010), and mitochondria (Pace 1983). They inhibit ribosomal protein synthesis in cells and alter cell membrane structure (McLaughlin and others 1977; Wannemacher and others 1997; Desjardins and Proctor 2007). The primary effect of trichothecenes is inhibition of mitochondrial translation, targeting the peptidyl transferase center (Freid and Warner 1982; Bouaziz and Martel 2009; Bin-Umer and others 2011). According to Shifrin and Anderson (1999), tichothecenes activate a cellular stress response named ribotoxic stress response. Rocha and others (2005) reported that trichothecenes have other effects such as inhibition of cell division, RNA and DNA synthesis, disruption of membrane integrity and structure, as well as mitochondrial function. According to Cundliffe and Davis (1977), T-2 prevents formation of the initial peptide bond, while DON inhibits the elongation step. Activity of peptidyl transferase and nucleic acid synthesis is inhibited by trichothecenes (McLaughlin and others 1977; Thompson and Wannemacher 1986). Trichothecenes interrupt cell membrane integrity and mitochondrial function induces programmed cell death in plants (Bunner and Morris 1988; Pace and others 1988; Rocha and others 2005) and apoptosis in animal cells (Yoshino and others 1997; Shifrin and Anderson 1999; Islam and Pestka 2003). Trichothecenes inhibit DNA and protein syntheses, but no mutagenic or carcinogenic effect has been reported. The main target affected by trichothecenes is the digestive system (Ueno 1983). DON and T-2 toxin affest immunity by inhibiting protein synthesis and cell proliferation (Bhat and others 2010). DON decreases antibody and immunoglobulin levels in the body (Richard 2007). Tricothecenes bind to ribosomes and inhibit protein synthesis (Thompson and Wannemacher 1986; Middlebrook and

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A review on mycotoxins in food and feed . . . Leatherman 1989). T-2 toxin interferes with the cell membrane function due to its amphipathic characteristic (Pritchard 1979). T-2 toxin alters cellular immune response, too (Ueno 1984). Extremely high dose of DON (more than 27 mg/kg BW) can cause death but low doses (50 g/kg BW) result in vomiting in animals. Pigs are the most sensitive animals to DON (Pestka 2007). Trichothecene toxicity in animals usually has the following symptoms: feed refusal, decreased feed conversion, weight loss, vomiting, severe dermatitis, abortion, bloody diarrhea, hemorrhaging, abnormal feathering, lesions at the edges of bird beaks, decreased egg production, and death. (Herrman and others 2002). Nausea, diarrhea, abdominal pain, dizziness, vomiting, and headache are symptoms of trichothecene mycotoxicosis in humans (Bhat and others 2010). As trichothecenes are lipophilic, they can be easily absorbed through skin (Coulombe 1993), pulmonary mucosa, and gut. Direct dermal application or oral ingestion of trichothecene causes rapid irritation to the skin or intestinal mucosa (McLaughlin and others 1977; Wannemacher and others 1997). As mentioned before, T-2 toxin has high toxicity. Exposure to high concentrations of aerosolized T-2 toxin results in pulmonary edema or lung lesions, while its oral intake causes direct damage to the intestinal mucosa (Creasia and others 1990; Nordby and others 2004). T-2 toxin lethal dose in mice is 5.2 mg/kg. According to Nordby and others (2004), inhalant exposure to grain dust in a grain production environment and mills might be responsible for some hormonerelated cancers. Grains (barley, oats, and wheat) have been shown to be contaminated with different levels of trichothecenes (DON and T-2 toxin) (Nordby and others 2004). Liver is the main organ for metabolism of the trichothecenes and the intestine is capable of doing some metabolic alteration to them. The metabolized toxins can be excreted in urine and feces (Matsumoto and others 1978). Acute oral, dermal, parenteral, or aerosol exposure to trichothecenes results in intestinal and gastric lesions (Wannemacher and others 1997). Trichothecenes have potential to be used as biological weapons. It was claimed by the U.S. government that in Southeast Asia and Afghanistan (during the 1970s) after exploding certain munitions (air-to-surface rocket, aerial bomb), a yellow and oily droplet mist spread in the air and fell on individuals at the explosion site and sickening them. Early symptoms of acute exposure to trichothecenes included nausea, vomiting, skin discomfort, weakness, and dizziness (Wannemacher and others 1997; Haig 1982). Diarrhea (at first watery brown and later grossly bloody) began within an hour, and after 3 h, sore mouth, bleeding gums, coughing and dyspnea, hematemesis, and epistaxis was reported (Haig 1982). De-epoxy DON is the main metabolite of DON (Yoshizawa and others 1986). De-epoxy DON, mainly produced by rumen and intestinal microflora and to a lesser content by liver, is exerted via animal urine and faeces (Gareis and others 1987; Swanson and others 1988). In contrast to pigs, mice, and rats, human gastrointestinal microflora are not able to transform DON and de-epoxy DON cannot be detected in human urine and faeces (Sundstol and Pettersson 2003). Although ruminants are less susceptible to DON (FinkGremmels 2008), but reduction in milk production, inhibition of reproductive performance and immune function were attributed to DON-contaminated feed (Bhat and others 2010). Compared to pigs, poultry are more resistant to DON but more sensitive to T-2 toxin. T-2 toxin causes reduction in egg production and increases incidence of cracked eggs (Devegowda and others 2005; Morgavi and Riley 2007). Scabby grain toxicosis or trichothecene

mycotoxicosis has been observed within hours after ingestion of contaminated food/feedstuffs such as corn, rice, wheat, and their products (Ueno 1970; Wang and others 1993). Chronic poisoning with group A trichothecenes results in immune system malfunction and significant changes in the blood cell count. T-2 toxin is the most important in group A. It can be metabolized by the gut microflora of mammals. Metabolized toxins are excreted via bile (WHO 2002). Immune system problems related to group A trichothecenes include depressed antibody formation, delayed hypersensitivity, changes in leukocyte counts, and depletion of selective blood cell progenitors. Group B trichothecenes cause reduction in dietary consumption in animals especially in pigs (WHO 2002; Bhat and others 2010).

FMNs In 1891, consumption of moldy maize (corn) contaminated with FMN caused a disease in equines (Haliburton and Buck 1986). Neurotoxic syndrome equine leukoencephalomalacia (ELEM) the massive liquefaction of the cerebral hemisphere of the brain and is attributed to some neurological manifestations such as lameness, nervousness, ataxia, aimless circling, facial paralysis, abnormal movement, and inability to drink or eat (Coulombe 1993; Marasas 2006). In 1988, a new class of mycotoxins was isolated from cultures of F. moniliforme (today known as F. verticillioides) and named FMN (Gelderblom and others 1988). FMNs are one of the main mycotoxin classes of concern produced by Fusarium species (Glenn 2007). Fusarium species are able to cause seedling diseases, stalk rots, ear rots, root rots, and kernel damage (Munkvold and Desjardins 1997). FMNs are primary amines and 4 series of FMN have been identified A, B, C, and P (Rheeder and others 2002; Cole and others 2003; Gelderblom and others 2007). “A” series members (FA1and FA2) have amides and the “B” series (FB1, FB2, FB3, and FB4) possess a free amine (Gelderblom and others 1992). Fumonisins of series “C” were isolated from wheat cultures of F. oxysporum (Seo and others 1996). Fumonisin B has the same structure as macrofusine (Norred 1993).

Occurrence of FMN Fusarium spp. are the most important field fungi (especially for maize) (Visconti 2001; Bankole and Adebanjo 2004) and invade a variety of plants. FMNs have been found in several agricultural products including corn, corn products, medicinal plants, herbal tea, dried figs, and bovine milk (Omurtag and Yazicioglu 2004; Sørensen and Elbaek 2005; Gazzotti and others 2009; Karbancioglu-G¨uler and Heperkan 2009; Seo and others 2009; Moretti and others 2010). Adverse effects and toxicity of FMN According to the Intl. Agency for Research on Cancer, FMN are classified as group 2B substances (possibly carcinogenic to humans) (IARC 1993b). There is not enough evidence for human health hazards related to FMN-contaminated food. However, a link between high incidence of human esophageal carcinoma and consumption of FMN-contaminated maize has been reported (Yoshizawa and others 1994; Abnet and others 2001; Marasas and others 2004). FMNs have cancer-promoting activity (Norred 1993; Munkvold and Desjardins 1997). FMNs are responsible for porcine pulmonary edema (Morgavi and Riley 2007). FB1 is a cancer promoter that causes neural tube defects in human babies (Marasas and others 2004; Bhat and others 2010). FB1 has hepatotoxic and nephrotoxic effects on animals. Chronic effects of FMN in animals include impairment in the basic immune function,

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A review on mycotoxins in food and feed . . . kidney and liver damage, respiratory difficulties, heart problems, reduction in milk production, weight reduction, and increase in mortality rate (Casteel and others 1994; Norred and others 1998; Diaz and others 2000). FMNs induce apoptosis in rat kidneys and cultured human cells (Seefelder and others 2003). Another sign of FMN toxicosis in dairy cattles included elevated serum enzyme activity of diagnostic liver enzymes that show mild hepatocellular injury (Fink-Gremmels 2008). Cooking fumonisins contaminated crops under alkaline conditions (such as production of tortillas from maize) results in formation of hydrolyzed FB1 that was reported in the feces of nonhuman primates (Shephard and others 1994). Fumonisins are poorly absorbed through gastrointestinal tract and rapidly cleared from the blood and excreted in bile (Soriano and others 2005). Accumulation of fumonisins in body tissues is low and little residues can be found in liver and kidney (Riley and Voss 2006). Ruminants were reported to have the minimum fumonisin absorption and show tolerance to Fumonisins that are poorly absorbed through of fumonisins (Voss and others 2007). FB1 is able to cross the placenta and reduced reproductive performance in mice (Gelineau-van Waes and others 2005). It was reported that FB1 reduce folate uptake by the embryos and decrease the amount of folate binding protein in the yolk sac membrane (Stevens and Tang 1997). FB1 has a similar structure to sphingoid bases (such as sphingosine) and acts as an inhibitor for ceramide synthetase, the key enzyme in biosynthesis of sphingolipid. Second type of lipids (sphingolipids) can be found in cell membranes and particularly in brain tissues and nerve cells (Soriano and others 2005). Inhibitory effect of FB1 results in accumulation of free sphingosine and sphinganine and subsequently cell death (Galvano and others 2002; Soriano and others 2005; Voss and others 2007). The inhibition of biosynthesis of glycosphingolipids can be observed a few hours after oral exposure to FB1 (Soriano and others 2005). This inhibition is responsible for the wide variety of health effects (such as high rate of human liver cancer and oesophageal cancer) due to the ingestion of fumonisins contaminated foods (Voss and others 2007). Ceramide synthase inhibition results in accumulation of sphinganine (Sa) and sphingosine (So) in serum, urine, and tissues. The Sa : So ratio in tissues is auseful biomarkers for exposure to FMN (Voss and others 2007). Another useful biomarker is the Sa concentrations of tissue, urine, or serum (Enongene and others 2002). FA1 is less cytotoxic than FB1 , but Van der Westhuizen and others (1998) reported FA1 as a ceramide synthase inhibitor. Haschek and others (1992) showed that FB1 (either orally or IV) resulted in hepatic changes such as necrosis and pulmonary edema in pigs. They mentioned that FB1 alters metabolism of sphingolipid, resulting in release of membranous materials into the blood circulation and consequently hepatocellular damage. Inhibition of ceramide biosynthesis has consequences such as: inhibition of hippocampus neurons cell growth, pulmonary edema, heart failure, liver lesions, and apoptosis (Soriano and others 2005). Besides, FB1 was reported as a possible carcinogen to humans with possible genotoxical effects (as a result of the activation of oxidative pathways) (Mobio and others 2000).

Occurrence of Mycotoxins in Malaysia Studies on mycotoxins in food/feedstuffs in Malaysia go back to 1965 when samples of peanuts and peanut cooking oils were investigated (Chong and Beng 1965). The most severe report on aflatoxin contamination of food in Malaysia was reported in Octo C 2013 Institute of Food Technologists®

ber 1988. There was an outbreak of acute hepatic encephalopathy resulting in death of 13 Chinese children in the northwestern state of Perak in peninsular Malaysia. The children have consumed Chinese noodle (joh see fun) and the symptoms include fever, vomiting, diarrhea, abdominal pain, and hematemesis. AFs were confirmed in the postmortem samples (Lye and others 1995). Since then, several studies have been carried out on different commodities. Due to the high health risks of AFs, they have been studied more often than other mycotoxins. Samples of imported and locally produced food have been examined. Surveys of aflatoxins in food from Malaysia showed that among all food products, peanuts are highly vulnerable to fungus and aflatoxin contamination, while in spices, oilseeds, and cereals, aflatoxin contamination is due to improper processing methods and poor storage conditions (Mat Isa and Tee 1984; Mat Isa and Abidin 1995; Abdullah and others 1998; Leong and others 2010).

Foods Cereals and grains Rice is the main product and staple food in Malaysia. Corn, wheat, and barley are not staple food grains in this country and are totally imported from Argentina, China, Indonesia, and Thailand (Warr and others 2008). In a survey on stored paddies, rice and rice flour samples were contaminated with AFs (MARDI 1992). However, AF levels in the positive samples were lower than 4 ng/g. A. flavus was also isolated from some of the AF-negative samples. Contamination of wheat flour from retail markets with AFs has been reported earlier (Abdullah and others 1998). The level of AFs in wheat flour samples was in the range of 11.25 to 436.25 ng/g. Abdullah and others (1998) conducted a survey on fungal colonies in starch-based foods from retail outlets in Malaysia. Aflatoxigenic colonies of Aspergillus were detected in wheat flour (20%), glutinous rice grains (4%), ordinary rice grains (4%), and glutinous rice flour (2%). Ordinary rice samples were contaminated with AFG1 (2.4%) and AFG2 (3.6%). Level of AFs in the positive samples collected from private homes ranged from 3.69 to 77.50 ng/g. About 1.2% of wheat flour samples was contaminated with AFB1 (25.62 ng/g), and 4.8% with AFB2 (11.25 to 252.50 ng/g), 3.6% with AFG1 (25.00 to 289.38 ng/g), and 13.25% with AFG2 (16.25 to 436.25 ng/kg). Higher incidence of AF contamination in wheat flour can be due to the following factors: first, presence of aflatoxin-producing Aspergillus spp. is more often seen in wheat flour than ordinary rice, and second, there are longer storage periods for wheat flour compared to other grain flours. Abdullah and others (1998) concluded that aflatoxin contamination occurred at the consumer level since the percentage of contaminated samples was higher at private homes compared to retail markets. Some of grains from Kuala Lumpur markets have been screened for AF contamination (Rahmani and others 2010). Rice and wheat samples were contaminated with AF : AFB1 (12%), AFB2 (23%), AFG1 (18%), and AFG2 (18%). The ranges of total AFs in the contaminated cereal samples were 0.01 to 5.9 ng/g. Yazdani and others (2011) collected samples of milled rice from retail markets in 4 provinces of Malaysia and screened them for Aspergillus and Eurotium spp. contamination. Isolates were then tested for their aflatoxin-producing ability. Only A. flavus isolate was able to produce AFB1 and AFB2 . In a survey by Hong and Nurim (2010), AFB1 and AFB2 were detected in 45% of corn-based products (0.2 to 101.8 ng/g). Samples were collected from imported and locally produced products at retail shops and local market in Kuala Terengganu. Wheat and barley samples from different markets in

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A review on mycotoxins in food and feed . . . the state of Penang were analyzed for the presence of Aspergillus spp. and AFB1 . Reddy and Salleh (2010) reported A. flavus and A. niger as the dominant aflatoxin-producing specie in all samples. AFB1 was detected in some of wheat samples at 0.42 to 1.89 ng/g and 1 barley sample at 0.58 ng/g. Barley and wheat samples were imported from Thailand and India, respectively (Reddy and Salleh 2010). Later in 2011, Reddy and his research group identified A. flavus and A. niger as the dominant aflatoxin-producing fungi in rice samples from Penang (Reddy and others 2011). They reported that rice-based products had the highest incidence of A. flavus. About 65.4% of A. flavus isolates produced AFB1 ranging from 1700 to 4400 ng/g, and 31% produced AFB2 ranging from 620 to 1670 ng/g. Their studies revealed that among the various examined food groups, cereal-based foods were the second most susceptible foods to AFB1 contamination. Peanut products were reported to be the most susceptible to AFB1 and 50% to 75% of cereal-based foods were contaminated with AFB1 with a mean level ranging from 1.25 to 3.86 ng/g. High levels of AFB1 contamination were detected in corn-based products (75%), rice (69.2%), wheat (64.2%), and oats (50%) (Reddy and others 2011). Malaysian commercial cereal samples including rice, wheat, and maize flakes were analyzed for AFs. The results showed that 33.3% of rice samples were contaminated with AFs ranging from 0.01 to 3.96 ng/g (Soleimany and others 2011). Later in 2012, Soleimany and others determined AFs in cereals from Malaysian markets using a more accurate method. About 70% of cereal samples were contaminated with AFs at levels of 0.15 to 4.54, 0.2 to 3.2, 0.26 to 2.59, and 0.12 to 1.94 ng/g for rice, wheat, barley, oat, and maize meal, respectively (Soleimany and others 2012a, b). As AFs were detected at low concentration in rice, therefore, rice and its products can be considered low-risk commodities in Malaysia. There were only a few reports on OTA in cereals from Malaysia. Rahmani and others (2010) found very low levels of OTA ranging from 0.03 to 5.32 ng/g in barley, rice, maize meal, and oat from Malaysian markets (Rahmani and others 2010). In the simultaneous determination of mycotoxins in cereals, Soleimany and others (2011) detected OTA in barley, wheat, maize meal, oat, and rice samples (0.1 to 5.32 ng/g) (Soleimany and others 2011). They also surveyed OTA contamination in commercial samples of rice, wheat, and maize flakes in Malaysia. Low levels of OTA were detected in the samples (0.49 to 5.71 ng/g) (Soleimany and others 2012a). Later, in a broader study, they used UPLC-MS/MS for the detection of mycotoxins in cereals and reported that some samples of rice, wheat, oat, barley, and maize meal were contaminated with OTA (Table 1). However, only 1 maize-meal sample exceeded the proposed regulatory limit of 5 ng/g (Soleimany and others 2012b). Rahmani and others (2010) also reported 2.8 to 73.11 and 2.38 to 24.43 ng/g of ZEN in rice and barley samples, respectively. However, they did not detect any ZEN contamination in wheat samples. Soleimany and others (2011; 2012a, b), who screened a broader range of cereal samples, detected ZEN in rice samples from 1.5 to 51.1 ng/g, while the lowest level was found in oat and wheat samples (Table 1). Soleimany and others (2011; 2012a, b) also analyzed cereal and grain samples from Malaysian markets for FMN. In 2011, they examined fumonisins B1 (FB1), fumonisin B2 (FB2), and fumonisin B3 (FB3) in rice, maize, and wheat samples. Wheat samples contained higher levels of FMN (80.63 ng/g). FMN contamination in rice samples ranged from 27.85 to 74.67 ng/g. Later in 2012, they surveyed rice, wheat, barley, oat, and maize meal samples and reported high levels of FB1 and FB2 in maize meal samples (48.2 to 209.3 ng/g) (Soleimany and others

2012a). In another study by Soleimany and others (2012b), low levels of FMN in cereals were reported (10.75 to 33.25 ng/g). Moazami and Jinap (2009) examined different wheat-based noodle products consumed in Malaysia for trichothecenes. Several types of noodles, composed of yellow alkaline, instant noodle, and white salted noodle, were analyzed. They reported a low occurrence of DON in commercial noodle products ranged from 0.627 to 1.243 ng/g. The incidence of DON was higher in imported noodles as compared to local products. Soleimany and others (2011, 2012a, b) reported DON contamination in cereal samples ranged from 12.5 to 81.2, 22.8 to 112.5, 35 to 109, 5.5 to 72.5, 6.72 to 100.2 in rice, wheat, maize, barley, and oat samples, respectively. More recently, Samsudin and Abdullah (2013) surveyed the occurrence of mycotoxigenic fungi and mycotoxins levels in red rice in Malaysia. Red rice, a fermented product of Monascus spp., was contaminated with mycotoxins due to its traditional preparation method. Monascus spp. as starter fungi were present in all 50 samples followed by Penicillium chrysogenum in 62%, Aspergillus niger in 54%, and Aspergillus flavus in 44% of the samples. Citrinin was detected in all samples ate levels of 0.23 to 20.65 mg/kg, AF in 92% of samples at 0.61 to 77.33 μg/kg, and OTA in all samples at 0.23 to 2.48 μg/kg. Hsuan and others (2011) studied distribution of Fusarium species on rice, sugarcane, and maize samples obtained from farms in different states in Malaysia. They identified 5 species, namely, F. sacchari, F. fujikuroi, F. proliferatum, F. andiyazi, and F. verticillioides. Izzati and others (2011) studied distribution of Fusarium species in maize grown in different locations throughout Malaysia. They reported 8 Fusarium species in samples from Johor, Selangor, Pahang, Pulau Pinang, and Sabah states. The most frequent species detected were F. proliferatum (29.9% isolates), F. semitectum (22.2% isolates), F. verticillioides (13.7% isolates), and F. subglutinans (12.6% isolates). According to Zainudin and others (2011), several species of Fusarium are associated with corn cultivated throughout Malaysia. They isolated 10 Fusarium species from corn plants cultured in 12 main corn growing locations in Malaysia. The most domenent species were F. proliferatum, F. subglutinans, F. verticillioides, and F. nygamai. The most contaminated samples with Fusarium sopecies were obtained in Semenyih, Selangor. Darnetty and other (2008) also isolated F. proliferatum, F. oxysporum, F. nygamai, F. semitectum, F. solani, and F. verticillioides from corn samples grown in 4 states of Malaysia, namely Pulau Pinang, Perlis, Sabah, and Sarawak.

Nuts and nut products In Malaysia, peanuts are a common dietary staple consumed in the raw, roasted, or baked form. Peanuts and peanut products have the highest consumption among the nuts produced in Malaysia. Penang adults consume an average of 0.77 grams of total nuts (including peanuts) per day (Leong and others 2010). Raw shelled peanuts can be found in almost all retailed outlets throughout the country and they are widely used as an ingredient in a variety of popular foods and dishes. Peanuts in Malaysia are partially supplied by local production; however, the majority are imported from India, Vietnam, and China. The occurrence of AF in nuts and peanut has been proven (Abdulkadar and others 2004). AF contamination of groundnut and groundnut oil was reported by Chong and Beng (1965). Consumption of such contaminated commodities exposes humans and animals to different levels of AF from nanograms to micrograms per day. Due to consumption of AF-contaminated groundnuts, an outbreak in pig farms in Melaka was reported in 1960 (Lim 1964).

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A review on mycotoxins in food and feed . . . Table 1–Mycotoxin levels (ng/g) in cereals and grains. Products Rice

Wheat

Wheat flour Wheat-based noodle Barley

Oat

Maize meal

Corn

AFs

OTA

FUZ

DON

ZEN

Reference

67.79 g/d) showed considerably high urinary AFM1 level compared to those with low intake. The study found a significant and positive relation between milk/dairy products consumption and urinary AFM1 level. Although the level of AFM1 in urine samples was not too high, long-term exposure to AFM1 may pose negative health effects.

Conclusions In order to protect Malaysian consumers from the risks of mycotoxin contamination, maximum permissible levels have to be generated for all food products and subjected to control by regulatory authorities. Of the food commodities surveyed, peanuts and their products are the ones most susceptible to growth and consequent mycotoxin contamination. Therefore, methods of control and mitigation of mycotoxins at storage in shops and homes should be developed. Intervention and reduction protocols for contamination in spice commodities are also needed. Rice, as one of the staple foods for Malaysians, was safe regarding mycotoxin contaminations. There is a lack of studies on animal-derived products such as milk and dairy products, meats, and eggs. Most of the studies carried out include surveys and exposure assessments. Hence, studies on interventions, preventions, and detoxifications are needed. Nevertheless, to evaluate the extent of the mycotoxin problem in Malaysia, there is a need for a more extensive and frequent observations of susceptible commodities from farm to table. Con-

sumer awareness programs are also needed to minimize the risk. Like other agriculture communities, mycotoxins contamination in food and feed can have considerable economic implications in Malaysia. Losses from rejected shipments and lower prices for lowquality products can devastate country export markets. Mycotoxin contamination also affects farmers by reduced income from lower selling prices for contaminated commodities. The economic impact of mycotoxin contamination on livestock production includes mortality, reductions in productivity, weight gain, feed efficiency, fertility, and ability to resist disease. The cost of mortality, morbidity, hospitalization, and health care services are also need to be taken into account. However, there is no report on economic analysis or the annual cost of mycotoxins contamination in Malaysia in terms of agricultural products spoilage, losses in livestock productivity, and human health effects, to date. Therefore, the economic losses have to be calculated and the costs of preventing mycotoxins through better production, harvesting, and storage practices must be weighed against the economic losses. High-risk agricultural commodities and high-risk population groups for selected mycotoxins need to be identified. The effect of mycotoxins on national economies and international trade must to be assessed.

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