2. Mycotoxins (Myco = of fungal origin)
• toxic substances produced by fungi (molds) growing on
crops/grains in the field or in storage.
• Secondary metabolites (chemicals) of a fungus that produce
toxic results in another organism.
• Unlike bacterial toxins, fungal toxins (mycoatoxins) are not
proteins and therefore are not usually detectable by the
immune systems of humans and animals
• Lack of visible appearance of fungus does not negate
presence of mycotoxins. Toxins can remain in the organism
after fungus has been removed.
• Cytotoxic: disrupt cell structures such as membranes, and
processes such as protein, DNA, and RNA synthesis.
• Can be heat stable, not destroyed by canning or other
processes.
3. Most fungi do not produce Mycotoxins
• Many fungi are edible
• Mushrooms are fungi
• Moldy feeds may be
degraded without
presence of mycotoxin, or
may be unaffected in
value.
• some material courtesy of
Mark Diekman
4. How was the concept of
Mycotoxins developed ?
• An outbreak of an unknown disease killed poultry
birds in 1960s
• This was named Turkey X disease
• After investigations it was finally traced to
mycotoxins in groundnut meal feed imported from
Brazil
• The feed was shown to contain a compound that
could cause cancer
• Today we know this mycotoxin by the name of
AFLATOXIN – A CLASS I CARCINOGEN
5. Brief History of Mycotoxins
• affected humans for thousands of years.
• Middle Ages had outbreaks of ergotism.
• Only in last 30-40 years have scientists been able
to isolate specific toxins from their fungal
source.
• Research ideas and methodologies, in this
field, change frequently, and data from 20 years
ago are considered questionable.
• Alimentary toxic aleukia-killed over I lakh people
• Stachybotryotoxicosis-killed thousands of horse
6. Information About Fungus
• Range from single cells to fruiting bodies that form
molds, mushrooms, smuts, and yeasts.
• Absorb nutrients from living or deceased
organisms, contain no chlorophyll.
• If multicellular, they have tubular filaments called
hyphae that branch out.
• Reproduce using spores.
7. How many mycotoxins are there?
• Today 300 - 400 mycotoxins are known
• Mycotoxins of human concern based on toxicity:
Aflatoxin
Deoxyniva-lenol (DON) or Vomitoxin
Zearalenone
Fumonisin
T-2 toxin
Ochratoxin A
8. • Species, breed
• Age
• Sex
• Nutritional status
• Other diseases
• Other mycotoxins
• Extent of exposure
9. Storage conditions that favor production
of mycotoxins:
Temperature (40 - 90o F ; 4 - 32o C)
Relative Humidity (> 70%)
Moisture (22-23% in grain)
Oxygen (1-2%)
12. Modes of Spore Transmission
• Airborne, wind or indoor ventilation systems.
• Attachment to insects of birds, thus transmitted
from plant to plant, or animal to animal, etc.
• Via transportation mechanisms such as trucks, crop
machinery, etc.
13. Route of infection
Ingestion/skin contact/ in halation
Blood stream & lymphatic system
Inhibit protein synthesis
Damage macrophages system
Inhibit particle clearance of the lungs
Increase sensitivity to bacterial endotoxins
14. Mycotoxins in corn
• Aflatoxins
Tricothecenes
• Fumonisins
O
O
OH
OH
HHH
H
O
H
OH
CH3
CH3
NH2
OHOH
OH
O
O
CH3CH3
O OH
OOH
O
O OH
O
OH
O
O
O
O
H
H
O
O
O
CH3
15. Common Mycotoxins
• Cool, wet weather
Fusarium Toxins
• Deoxynivalenol (DON or Vomitoxin)
– Considered a “marker”
• T-2 toxin (T-2)
• Zearalenone (F-2)
• Fumonisin
• Hot, humid weather
• Aflatoxin
18. Acute toxicity
• Deterioration of liver and kidney
functions, leading to death in extreme
cases
• Interference with protein synthesis
• Skin sensitivity affected
• Necrosis of skin
• Immunodeficiency
• Neurotoxins cause trembling in small doses
and brain damage or death in slightly higher
doses
19. Chronic toxicity
• Induction of cancer (Liver, oesophagus)
• Induction of tumors
• Induction is never detected at the time of
ingestion and remains undetected till the disease
is advanced
Mutagenic & Teratogenic toxicity
• Replication of DNA is affected producing
mutagenic and teratogenic effects
21. Potential uses of mycotoxins
• Medical application –
• Trichothecenes are known to possess
antileukaemic activity;
• zearalenone derivatives have been
considered as potential treatment for
menopausal syndrome in women;
• Agriculture application –
derivatives of zearalenone as growth
promoter in sheep and cattle; other
have been considered for use as
herbicides and insecticides.
22. Effects of Molds/Mycotoxins
Molds - Decrease digestibility (5%)
- Decrease production (5-10%)
Mycotoxins – Impact on milk production, weight
-- gain greater than molds
Mimic other herd health problems
– Depressed immune system
– Off-feed
– Diarrhea
– Hemorrhaging
– Abortions
– Reproduction issues
23. Health effects of mycotoxins
Acute and chronic effects on both humans and
livestock
Mycotoxins are believed to be among the most
potent known carcinogens
Effect range from immediate toxic responses &
immunosupression to potential long-term
teratogenic, estrogenic, & carcinogenic effects.
Possible health effects due to airborne exposure
(exposure to airborne spores with mycotoxins)
24. Human mycotoxicosis
In 1967, 26 Taiwanese in a farming community
became ill after eating contaminated rice; 3
children died.
Cause of death: Contaminated rice showed >200
µg aflatoxin B1/kg.
In 1974, an outbreak of hepatitis in India
affected 400 people resulting in 100
deaths;
Cause of death: aflatoxins in corn ( >15 mg/kg)
25. Human mycotoxicosis
In 2004, one of the largest aflatoxicosis
outbreak occurred in rural Kenya resulting in
317 cases and 125 deaths.
Cause of death:
corn contaminated with 4,400 µg/kg of
aflatoxin B1, 220 times higher than Kenyan
regulatory limit for food.
26. Mycotoxin Toxicity: Effect on Humans
• Physiological and pathological changes
• Food poisoning
• Inhibition of protein synthesis & Alteration of capacity of
cells to proliferate
• Increase of tryptophan in blood and brain (affects
appetite, muscular co-ordination and sleep
• Nausea ,Vomiting
• Headache
• Abdominal pain, Diarrhoea Giddiness
• Convulsions
• Reproductive and mammary changes
• Role in hormonal balance and breast cancer
• Precocious pubertal changes in children
• Breast enlargement in boys
• Role in cancer
• Immunosuppressor
27. Symptoms of Mycotoxicosis
1. Drugs and antibiotics are not effective in treatment.
2. The symptoms can be traced to foodstuffs or feed.
3. Testing of said foodstuffs or feed reveals fungal
contamination.
4. The symptoms are not transmissable person to person.
5. The degree of toxicity is subject to persons age (more
often in very young and very old), sex ( more often in
females than males)and nutritional status.
6. Outbreaks of symptoms appear seasonally.
28. Mycotoxin Effects on Animals
• Feed refusal.
• Impaired animal health, resulting in reduced
production of eggs, milk, weight gain, etc.
• Metabolites are passed through the milk in
cheese, dry milk, and yogurt.
• Disease.
• Death in animals.
29.
30. Fusarium
plant pathogens in soil
• corn, wheat, barley, beans,
• Trichothecene toxins target the
circulatory, alimentary, skin, and nervous
systems.
F. graminearum- Wheat
Causes scab damage to kernels and head blight.
Produces deoxynivalenol (DON), also called
vomitotoxin.
31. F. graminearum in Maize (Corn)
• Produces the toxins: DON & zearalenone
(ZEN), and T-2 toxins.
• Have damaging effects on plants, humans,
and other animals with monogastric digestive
processes.
Zearalenone T-2 toxin
32. F. moniliforme-corn
• Plant pathogen most associated with corn. Also found
in rice, sorghum, yams, hazelnuts, pecans, and cheeses.
• Diseases “crazy horse disease” in horses,
pulmonary edema in pigs,
liver cancer in rats,
bone malformation in chicks and pigs.
esophageal cancer in humans.
• Other toxins produced include fusaric
acid, fusarins, and fusariocins.
• Advisory levels are 5 ppm in animal feed.
33. DON and T-2 Toxin
• tricothecenes of wheat, grain, and barley.
• necrosis and hemorrhage of the digestive
tract, decreased blood production in the bone
and spleen, and changes to reproductive systems.
• In poultry, causes reduced egg production, beak
lesions, and abnormal feathering
• Optimal temperature range is between 70 and 85
degrees Farenheit.
• Advisory level of DON is 1 ppm.
34. Alimentary Toxic Aleukia (ATA)
• During World War II, in Soviet Union, corn grain left to
over-winter becomes contaminated with T-2 toxin.
• Severe mycotoxicosis occurs.
• burning in the mouth, esophagus, tongue & stomach.
• Bone marrow formation is halted & anemia develops.
• Hemorrhage of nose, gums,
mouth and stomach occurs.
35. Zearalenone
Species : Fusarium roseum, F.graminearum, F.
poae, F. culmorum
Food affected: corn, wheat, barley, oats
Interesting facts:
• Zearalenone has estrogenic effects.
36. Zearalenone
Mimics the body’s production of estrogen.
Lengthened or absent estrous cycle
Causes feminization of male animals.
Prepuberal gilts show enlarged, swollen vulva as if
in estrus
Interrupted reproductive cycles in
female swine
Prolapse of the vulva possible
Little or no effect on growth
Pigs are especially sensitive, poultry
and cows show little sensitivity.
37. Alternaria Toxins
• wheat, sorghum, and barley.
• Also fruits and vegetables that can cause spoilage in
refrigeration.
• Toxins include: alternariol, alternariol monomethyl
ether, altenuene, tenuazonic acid, and altertoxins.
• Little is know of these toxins; but, toxic effects are
seen in rats, chicks, ducklings, and turkeys.
38. Claviceps Toxins
• Earliest recognized mycotoxicosis caused
by C. purpurea, with ergot mold.
• Outbreaks have been reported since 857
A.D.
• Humans consumed bread baked with
grain containing ergot spores, which
produced lysergic acid diethylamide
(LSD) symptoms and hallucinations.
39. Ergot Poisoning (St. Anthony’s Fire)
• Disease of barley, oats and wheat.
•Grains are replaced by ergot sclerotia that contain toxins.
•Main toxin is called ergotamine.
•Named for the belief that a pilgrimage
to the shrine of St. Anthony would
alleviate the symptoms. Ergotamine
Species:
Claviceps purpurea, and Aspergillus and Penicillium
Affected foods :- rye, barley, wheat, and oats
Interesting facts:
• First documented case of ergot poisoning was in 857. [5]
• Ergot contains a chemical precursor to lysergic acid
(LSD).
40. Ergot Poisoning (Cont…)
•Animal symptoms:
• Dry gangrene,
• Internal bleeding,
• Vomiting,
• Constipation,
•Diarrhea, and
•In pigs:
abortion of fetuses.
Human symptoms:
Gastrointestinal
stress; convulsions;
Fetal abortion;
Extreme burning and
Cold sensations in
Fingers, hands, & feet;
Gangrene of
extremitie
41. Aspergillus Toxins
• more than 100 species, 50 of which are
known to produce mycotoxins.
• Aspergillus niger is used to make artificial
citric acid; one use is in soft drinks.
• Miso, soy sauce, and sake use strains of A.
oryzae.
Cotton, peanut, maize
spices, pistachoos
42. Aspergillus and Aflatoxin
• Aflatoxicosis: caused by high doses in short
intervals or low doses in high intervals.
• 1961, caused the deaths of over 100,000 turkey
poults: “Turkey X disease”.
• Toxin was traced to contaminated Brazilian
peanut meal in poultry feed.
• Grows best between 80-90 degrees Farenheit.
• Damage to grain increases
likelihood of fungal growth.
43. 1. Sources :Corn, peanuts
2. Factor favoring production of aflatoxins
a. Temperature : 25-30 c
b. Grain moisture
highly toxic carcinogenic secondary metabolites
produced by fungi namely:-
1. Aspergillus flavus
2. Aspergillus parasiticus
3. Aspergillus nomius
44. Types of Aflatoxins
• Naturally produced Aflatoxins –B1, B2, G1, G2
• They undergo modifications during cellular
metabolism and processing of foods to
produce several derivatives such as
M1, M2, P1, etc.
International limit 15mg per kg food
45. Aflatoxin B-1
• most potent aflatoxin
• Classified as Class I Human carcinogen
• selectively targets human gene
p53 described as ‘Guardian of the genome’
• Definite link to cancer in animals.
• Primarily attacks the liver, in cases of cirrhosis, necrosis,&
carcinomas with a secondary affect immune suppression.
• Risk factor for neonatal jaundice, in areas of maternal
consumption.
• Does not stay in the body for long periods of time, usually
excreted within 96 hours, in animals.
• In milk, for human consumption, advisory level is .5 ppb.
46. AFLATOXIN EFFECTS
Inhibits protein synthesis
Poor gain
Liver damage
Susceptibility to Infection
Residues / carcinogenicity
Reproduction in swine not
primarily affected
47. Penicillium Toxins
• Large genus with over 150 species.
• Discovered antibacterial properties within
genus, causing production of penicillin.
• 100 species have mycotoxins.
• Nine specific toxins affecting human health
are citreoviridin, citrinin, cyclopiazonic
acid, ochratoxin A, patulin, penitrem A, PR
toxin, Roquefortine C, and, Secalonic acid D.
48. Penicillium Toxins (Cont.)
• Separated into two groups: those that affect
liver and kidneys, and those that are
neurotoxic.
• Liver and kidney toxins are asymptomatic and
cause overall animal debility.
• Neurotoxins cause visible
trembling.
http://farma.qfb.umich.mx/images/penicillium.jpg
49. Ochratoxin A and Citrinin
• Affects kidney function.
• Causes Balkan nephropathy and Yellow Rice Fever in humans.
• Chickens, turkeys, and ducklings are affected by
ochratoxicosis, causing poor weight gain, egg output, and poor shell
quality.
• Ochratoxin sources are peanuts, pecans, beans, dried fruit and
dried fish.
• Citrinin sources are in wheat, rice, corn, and flour.
• Citrinin is most associated with horses, pigs, dogs, and poultry.
Ocratoxin A Citrinin
50. Ochratoxin A
Species: P. Verrucosum and A. ochraceus
Food affected: Cereals, coffee beans, and grapes.
Interesting Facts: Ochratoxin can be transmitted from
pork to humans by eating pork that is fed with
contaminated food.
51. Cyclopiazonic Acid (CPA)
• Found in corn and peanuts in Georgia.
• Chief species from Penicillium causes cheese
spoilage.
• Causes fatty degeneration in liver and kidneys
in animals, chickens are very susceptible.
• May act synergistically with aflatoxin.
CPA
52. Types of Tests for Mycotoxins
Quick Test (Qualitative)
Immunoassays (Elisa tests)
Thin Layer Chromatography (TLC)
Use: (Detect Specific Mycotoxin)
Confirmatory Tests (Quantitative)
High Pressure Liquid Chromatography(HPLC)
Use: Determine level of mycotoxins
Detect several mycotoxins
53. Managing Moldy/Mycotoxin Problems
Ensure adequate levels of vitamins (A,E,B-1) and
minerals (Se,Cu,Zn,Mn).
Include aluminosilicate or bentonite in ration
Dilution is the solution.
Reduce intake of contaminated feeds.
Eliminate highly contaminated feeds.
Remove moldy layers of feed before feeding.
54. Quick Toxin Review
Organ System Affected Toxin(s)
Vascular Aflatoxin
Digestive Aflatoxin, T-
2toxin, Vomitotoxin
Respiratory Trichothecenes
Nervous Trichothecenes
Cutaneous Tricothecenes
Urinary Ochratoxin A, Citrinin
Reproductive Zearalenone, T-2 toxin
Immune Many
55. Future Fight Against Mycotoxins
• Have farmers select strains resistant to
contamination.
• Scientists hope to genetically engineer plants
resistant to fungal infection.
• Use feed additives that sequester the toxins
and prevent absorption from the
gastrointestinal tract.
