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DIONNE FLETT EMMA GILL FUNGAL TOXINS IN FOOD APRIL 2002. Introduction Fungal toxins, also referred to as mycotoxins, are secondary metabolites produced by moulds. The most important mycotoxins include: 1. Aflatoxins 5. Fumonisins
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DIONNE FLETT EMMA GILL FUNGAL TOXINS IN FOOD APRIL 2002
Introduction Fungal toxins, also referred to as mycotoxins, are secondary metabolites produced by moulds. The most important mycotoxins include: 1. Aflatoxins 5. Fumonisins 2. Tricothecenes 6. Tremorgenic 3. Ochratoxins Toxins 4. Zearelenone 7. Ergot Alkaloids
Mycotoxin Overview • 1. Aflatoxins • Produced by Aspergillus spp. and can grow on most foods/crops • Aflatoxins B1 & B2, (B1 is most toxic and is discussed in more detail later), are produced by A. flavus, A. parasiticus & A. nomius • Aflatoxins G1 & G2 are produced by A. parasiticus & A. nomius • Aflatoxins M1 & M2 are produced from the B1 & B2 aflatoxins & found in the milk of lactating animals • The letters denoted by the aflatoxins indicate the colours in which they are seen under UV light. (B=blue & G=green)2
Mycotoxin Overview • 2. Tricothecenes • Produced by Fusarium sporotrichioides, F. graminearum, F. poae & F. culmorum • These toxins may also be produced by Myrothecium, Trichothecium, Cephalosporium & Stachybotrys spp.4 • Found in corn, barley, wheat & rice • Included in tricothecenes are: • * T-2 Toxin * Diacetoxyscirpenol (DAS) • * Nivalenol * Deoxynivalenol (DON)1 • T-2 toxin is most toxic (discussed in more detail later)
Mycotoxin Overview • 3. Ochratoxins • Group of 7 mycotoxins • Ochratoxin A, (OTA), most toxic & is associated with kidney disease • OTA produced by Penicillium verrucosum & Aspergillus ochraceus1 • Contaminates barley, corn, peanuts & coffeebeans4 • 4. Zearelenone • Produced by Fusarium culmorum • Recently has been linked with stimulation of cancer cells in breast tissue • Contaminates cereal grains2 Fig.1. Fig.2. Structure of Structure of Zearelenone3 OTA3
Mycotoxin Overview • 5. Fumonisins • Produced by Fusarium verticillioides, F. moniliforme & F. proliferatum • Fumonisins B1 & B2 are both possible human carcinogens but Fumonisin B1 is most toxic • Fumonisins have been found to contaminate asparagus, beer & rice1 Fig.3. Structure of Fumonisins B1 & B23
Mycotoxin Overview • 6. Tremorgenic Toxins • Example of such toxins include, lolitrem B toxin3 • Produced by Acremonium ,Claviceps & Penicillium spp. • Affects the CNS and causes tremors2 • 7. Ergot Alkaloids Fig.4. Structure of lolitrem B toxin3 • Examples of theses toxins include ergotamine & ergostine • Produced by Claviceps purpurea & Acremonium spp.3 • Found in grasses & cereal grains in which they replace the developing ovary • If exposed to humans can result in convulsions & gangrene • Outbreak in Middle Ages termed ‘St Anthonys Fire’4 Fig.5. Structure of ergotamine3
Aflatoxin B1 • Produced by Aspergillus flavus, A. parasiticus & A. nomius6 • Found in nuts & oilseeds, especially corn, peanuts & cottonseeds6 • Preharvest contamination of above crops occurs via temperatures greater than 70oC, insect damage & severe, prolonged drought5 • Health Effects2,4,5,6,7 • Aflatoxin B1 causes: • * acute liver damage • * cirrhosis • * liver carcinogen • * immunosuppresive effects • * epidemics of acute toxic hepatitis
Mechanism of Action2 • Aflatoxin B1 is metabolised by the microsomal mixed function oxidase system in liver, leading to formation of highly reactive intermediates, one of which is 2,3-epoxy-aflatoxin B1. These reactive intermediates bind to DNA & disrupt transcription, resulting in abnormal cell proliferation. This leads to mutagenesis or carcinogenesis. • This toxin also inhibits O2 uptake in tissues by acting on electron transport chain & inhibiting various enzymes, resulting in a decreased production of ATP. • Hepatitis B virus can be an additional factor but evidence concerning this is contradicting. • Aflatoxin B1 is biotransformed by microsomal cytochrome monooxygenase.
Incidence of Disease2,5,6,7 • India 1974 - 100 out 400 people who contracted hepatitis died • because of aflatoxins • - corn contaminated with A. flavus (~15mg/kg) • - died mainly from gastrointestinal haemorrhage • In the North Western Malaysian state of Perak, 13 children died due to aflatoxin poisoning • Aflatoxin related deaths reported in Africa due to high cosumption of mouldy grain & brewery products • Death rates due to aflatoxins in China & Africa range from 10-60% • ~ 25,000 deaths in China & Sub Saharan Africa caused by human hepatocellular carcinomas attributed to risk factors such as high daily intake of aflatoxins & high incidence of hepatitis B
T-2 Toxin • Produced by a number of Fusarium spp. including, F. aqcuminatum, F. crookwellense, F. graminearum, F. poae, F. sambucinum & F. tricinctum3 • Contaminates cereal grains, wheat, rye, barley, corn & bread2 • Health Effects • Initial clinical symptoms include; vomiting, diaorrhea, haemorrhaging, breathing difficulty, chest pain, blisters, headaches, fatigue & dizziness2 • Conditions caused by this toxin:2,5,7 • * Alimentary Toxic Aleutia (ATA) • * neurotoxicity • * inflammations
Alimentary Toxic Aleutia (ATA)5 • Disease caused by ingestion of T-2 toxin and resembles radiation poisoning. • Divided into four stages: • * stage 1: 3-9 days after exposure. Symptoms; skin • inflammation, sore throat, abdominal pain, • salivation, headaches, weakness & rapid heart • rate • * stage 2: bone marrow depression, anaemia, decreased platelet & white • blood counts • * stage 3: bleeding from gums, GI tract & nose. Increased susceptibility • to infectious agents (possible death) • * stage 4: improvement in bone marrow function. Patient usually recovers • if this stage is reached
Mechanism of Action2,3 • T-2 toxin inhibits the synthesis of protein, RNA & DNA synthesis. The toxin binds to polysomes & ribosomes & peptide linkages are interrupted. The initiation & termination sequences are diminished & the ribosomal cycle is disrupted. • T-2 toxin disrupts the transport of amino acids, nucleotides & glucose, along with the activity of Ca - K channels on cell membranes. • Succinate Dehydrogenase activity is suppressed by the T-2 toxin, & mitochondrial electron transport is inhibited.
Incidence of Disease • 1944 in Russia during World War II, food shortages meant people ate overwintered Mouldy grain cereals5,7 • This lead to an outbreak of alimentary toxic aleukia. • Symptoms were severe haemorrhaging, anaemia and death • Sick houses • immunosuppressive diseases like leukaemia develop • every member of the household is effected • caused by Fusarium in dust2,7
Prevention • Aflatoxins3,4 • Determine levels that are unlikely to be of a health concern • European Union set aflatoxin B1 levels at 2ppb with a maximum upper limit of 4ppb in agricultural commodities • US Federal Food Drug & Cosmetic Act section 402a set levels at 20ppb in foods & feeds. Grains & nuts were limited at 1µg/kg • By 1994, 177 countries had regulations for aflatoxins in foods & feeds • T-2 Toxin3,4 • As yet there is no legislation regarding Fusarium spp. & T-2 toxin
References 1. Creppy, Edmond E. (2001) Update of Survey ,Regulation & Toxic Effects of Mycotoxins in Europe, Toxicology Letters, In Press, Uncorrected Proof 2. Doyle, Michael P., Beuchat, Larry B. & Montville, Thomas J. (1997) Food Microbiology Fundamentals & Frontiers, ASM Press, Washington D.C. Pp393-431 3. Hussein, S. Hussein & Brasel, Jeffrey M. (2001) Toxicity, Metabolism & Impact of Mycotoxins on Humans & Animals, Toxicology, 167 pp101-134 4. Kuiper-Goodman, T. (1995) Mycotoxins: risk assessment and legislation, Toxicology letters, 82/83, pp853-859 5. Lederberg Joshua., (2000) Encyclopedia of Microbiology, 2nd Edition, Vol 3 L-P, Academic Press, pp338-347 6. Mossel,D.A.A., et al,(1995) Essentials of the Microbiology of Foods: A textbook for advanced studies, J.Wiley & sons, pp154-158 7. Robinson, Richard K. (2000) Encyclopedia of Food Microbiology, Academic Press, London, pp339-342, pp1518-1523