1. DIONNE FLETT
EMMA GILL
FUNGAL TOXINS IN FOOD
APRIL 2002

2. Introduction
Fungal toxins, also referred to as mycotoxins, are secondary metabolites produced by moulds. The most important mycotoxins include:
1. Aflatoxins Fumonisins
2. Tricothecenes Tremorgenic
3. Ochratoxins Toxins
4. Zearelenone Ergot Alkaloids

3. 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

4. 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)

5. Mycotoxin Overview 3. Ochratoxins 4. Zearelenone 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 Fig.2. Structure of
Structure of Zearelenone3
OTA3

6. 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

7. 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

8. 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

9. 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.

10. Incidence of Disease2,5,6,7
India 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

11. 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

12. 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

13. 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.

14. 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

15. Prevention Aflatoxins3,4 T-2 Toxin3,4
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

16. 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. Pp
3. Hussein, S. Hussein & Brasel, Jeffrey M. (2001) Toxicity, Metabolism & Impact of Mycotoxins on Humans & Animals, Toxicology, 167 pp
4. Kuiper-Goodman, T. (1995) Mycotoxins: risk assessment and legislation, Toxicology letters, 82/83, pp
5. Lederberg Joshua., (2000) Encyclopedia of Microbiology, 2nd Edition, Vol 3 L-P, Academic Press, pp
6. Mossel,D.A.A., et al,(1995) Essentials of the Microbiology of Foods: A textbook for advanced studies, J.Wiley & sons, pp
7. Robinson, Richard K. (2000) Encyclopedia of Food Microbiology, Academic Press, London, pp , pp