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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

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Dionne flett emma gill fungal toxins in food april 2002

DIONNE FLETT

EMMA GILL

FUNGAL TOXINS IN FOOD

APRIL 2002


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


Dionne flett emma gill fungal toxins in food april 2002

  • 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


Dionne flett emma gill fungal toxins in food april 2002

  • 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)


Dionne flett emma gill fungal toxins in food april 2002

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


Dionne flett emma gill fungal toxins in food april 2002

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


Dionne flett emma gill fungal toxins in food april 2002

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


Dionne flett emma gill fungal toxins in food april 2002

  • 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


Dionne flett emma gill fungal toxins in food april 2002

  • 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.


Dionne flett emma gill fungal toxins in food april 2002

  • 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


Dionne flett emma gill fungal toxins in food april 2002

  • 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


Dionne flett emma gill fungal toxins in food april 2002

  • 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


Dionne flett emma gill fungal toxins in food april 2002

  • 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.


Dionne flett emma gill fungal toxins in food april 2002

  • 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


Dionne flett emma gill fungal toxins in food april 2002

  • 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


Dionne flett emma gill fungal toxins in food april 2002

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


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