Mycotoxins Flashcards
Fungal spores are spread by:
- Insects
- Rodents
- Other animals
What leads to the decomposition of organic substrates by fungi?
Spores germinate and the metabolic activity accompanying the growth and development of mould leads to decomposition of organic substrates.
What are mycotoxins?
Secondary metabolites produced by fungal species belonging to various genera such as Aspergillus, Penicillium and Fusarium
What is the toxicological significance of mould contamination?
- Thriving mould species produce toxic secondary metabolites known as mycotoxins.
- Consumption of mycotoxins can lead to mycotoxicoses and some are potent carcinogens.
- Oxidized products with very strong affinity for DNA
- There is proven relationship of mycotoxins consumption with teratogenesis, carcinogenesis, and mutagenesis
When are crops (grains & nuts) most susceptible to mycotoxigenic fungi infestation?
Under high temperature and humidity
Humidity; moisture; time; aerobic (optimal for mould growth)
- Also present in animal products (e.g., milk, liver and kidney) from animals fed contaminated crops (e.g., Aflatoxin B1 & M1; Ochratoxin A; fumonisins)
- RTE foods are popular and may also contain mycotoxins.
Give two examples of mycotoxins of Aspergillus.
- Aflatoxins (B, M, G) - carcinogenic
- Ochratoxins
Name two mycotoxins of Penicillium.
- Erythroskyrine (interferes with growth development of infants)
- Islanditoxin
Name two mycotoxins of Fusarium.
-
Trichothecenes (interferes with growth development of infants)
- e.g., deoxynivelenol (a.k.a. vomitoxin); nivelenol T-2 and HT-2
- Zearalenone (endocrine disrupter)
Also Enniatins (ENNs) and beauvericin (BEA).
Name a mycotoxin not from Aspergillus, Penicillium, nor Fusarium.
Ergot (localized painful inflammatory effect)
What is the health effect of aflatoxin? [3]
Aspergillus moulds
- Acute toxicity
- Hepatic cancer
- Reye’s syndrome
What is the health effect of trichothecenes? [3]
Fusarium moulds
- Acute toxicity
- Cancer
- Alimentary toxic aleukia
e.g., deoxynivalenol (a.k.a. vomitoxin)
What is the health effect of Ochratoxin? [3]
Aspergillus moulds
- Cancer
- Kidney disorders
- Hepatic damage
What is the health effect of Ergot alkaloids?
Ergotism
May be convulsive or gangrenous
Name the associated health risk.
Aflatoxin B1
Mycotoxin
Carcinogen Group 1
Associated health risk
Aspergillus
Name the associated health risk.
Deoxynivalenol [3]
Mycotoxin
- Delayed growth
- Immunotoxic effects
- Hematotoxic effects
Associated health risk
a.k.a. vomitoxin
Name the associated health risk.
Ochratoxin A
Mycotoxin
Carcinogen Group 2B
Associated health risk
Aspergillus
Name the associated health risk.
Zearalenone
Mycotoxin
Reproductive issues in farm animals (endocrine disruptor)
Associated health risk
Fusarium mould
Name the associated health risk.
Fumonisins [3]
Mycotoxin
- Teratogenic
- Hepatotoxic
- Nephrotoxic
Associated health risk
Fusarium mould
Name the associated health risk.
Nivalenol, T-2 and HT-2 [3]
Mycotoxin
Toxicological effects on:
- GI tract
- Immune system
- Endocrine system
Associated health risk
Trichothecene produced by Fusarium moulds.
Name the associated health risk.
Enniatins and beauvericin [1]
Mycotoxin
Cytotoxic
Associated health risk
Fusarium mould
Name the mycotoxin.
Carcinogen Group 1
Associated health risk
Mycotoxin
Aflatoxin B1
Mycotoxin
Name the mycotoxin
Delayed growth as well as immunotoxic and hematotoxic effects
Associated health risk
Mycotoxin
Deoxynivalenol
Mycotoxin
Name the mycotoxin.
Carcinogen Group 2B
Associated health risk
Mycotoxin
Ochratoxin A
Mycotoxin
Name the mycotoxin.
Reproductive issues in farm animals
Associated health risk
Mycotoxin
Zearalenone
Mycotoxin
Name the mycotoxin.
Teratogenic, hepatotoxic, and nephrotoxic
Associated health risk
Mycotoxin
Fumonisins
Mycotoxin
Name the mycotoxin.
Toxicological effects on GI tract, immune, and endocrine systems
Associated health risk
Mycotoxin
Nivalenol, T-2 and HT-2
Mycotoxin
Name the mycotoxin.
Cytotoxic
Associated health risk
Mycotoxin
Enniatins and beauvericin
Mycotoxin
Describe the frequency of mycotoxin food recalls.
- Grains: AFB1(12); Ochratoxin A (6); HT-2 toxin (3)
- Nuts: AFB1(13)
- Dairy: AFM1 (8)
- Herbs & spices: AFB1 (1); Ochratoxin A (4); HT-2 toxin (2)
- Vegetables: AFB1 (2)
Data is from around the year 2000. Global problem.
Grains, dairy, and nuts were primary sources of aflatoxin infestation.
Describe the toxicity of deoxynivalenol.
- Biotransformation process of a toxin (very hydrophobic) that is not as toxic as its metabolite
- Phase I enzymes oxidize
- Phase II enzumes conjugate oxidized products so it can be excreted
- In many cases - this is not a balanced activity between Phase I and II enzymes so you end up with a build-up of oxidized products.
- Enzymatic antioxidant mechanisms (e.g., superoxide dismutase) function to inactivate the hydrogen peroxide or the oxidized molecule.
- Lack of cofactors (e.g., zinc, iron, etc) due to micronutrient deficiency, then these enzymes will not function efficiently
- Non-enzymatic antioxidant mechanisms contribute too (e.g., vitamin C is a water soluble reducing agent; vitamin E is a lipid-soluble antioxidant, but it will become a free-radical when saturated unless it is reduced by vitamin C - vitamin C takes on the free radical and is eliminated in the urine and vitamin E is regenerated to its original lipid-soluble antioxidant form)
Which aflatoxin is the most powerful and lethal natural occurring liver carcinogen?
Aflatoxin B1
What is aflatoxin B1?
The most powerful and lethal natural occurring liver carcinogen.
Which aflatoxins are usually found in food?
- B1
- B2
- G1
- G2
- M1
- M2
M1 and M2 are metabolic products of B1 and B2, respectively.
B group gives characteristic blue fluorescence in UV light while the G group gives green fluorescence.
What foods are aflatoxins present in?
- Cereals
- Maize grains
- Peanuts
Also dairy when animals are fed contaminated grains.
What are aflatoxins?
- A group of approximately 20 related fungal metabolites produced mainly by Aspergillus flavus and Aspergillus parasitica.
Describe the life cycle of Aspergillus flavus on maize.
What is turkey-X disease?
Aflatoxin was first discovered by observing a “plague” on many turkey farms, particularly in England in the early 1960’s, where the turkeys died rapidly due to being fed peanut meal contaminated with Aspergillus flavus and related species .
Describe the structure of B group aflatoxins.
- Bifuranocoumarins fused to a cyclopentanone
- The cyclopentanone ring gives the molecule greater toxic potency compared to the lactone in G2.
- The dihydrofurofuran moiety is also toxic - reduction of this portion reduces activity (B1 vs B2)
Describe the structure of G group aflatoxins.
- Bifuranocoumarin fused to a six-membered lactone (lower toxic potency than the cyclopentanone in B group aflatoxins)
- The dihydrofurofuran moiety is also toxic - reduction of this portion reduces activity (G1 vs. G2)
Describe the structure of M group aflatoxins.
- Bifuranocoumarin fused to cyclopentanone
- The dihydrofurofuran moiety is also toxic - reduction of this portion reduces activity (B1 vs B2)
- M1 and M2 are metabolic products of B1 and B2
What is the LD50 of aflatoxin B1?
0.5 mg/kg
All peanut butter contain alfatoxins.
True or False?
True.
It is usually far below the recommended safe level.
Peanut butter does not naturally contain aflatoxin.
True or False?
False.
All sources of peanut butter contain minute quantities of aflatoxin, but it is far below the recommended safe level.
Aflatoxin can be found in milk.
True or False?
True.
It can be found in the milk of animals which are fed contaminated feed.
Alfatoxin is not found in milk.
True or False?
False.
The toxin can be found in the milk of animals which are fed contaminated feed.
When will the FDA consider action? (W.r.t. aflatoxins)
If aflatoxin levels exceed:
Describe the route of toxicity of aflatoxins.
- Liver: a lipophilic organ: store and concentrates all compounds carried by blood stream.
- Aflatoxins are converted to reactive 8,9-epoxide form (cytochrome P450).
- Capable of binding both DNA and proteins.
- Binds to N7 position of guanines.
- May lead to hepatocellular carcinoma (HCC).
- High concentration intake of aflatoxin may induce acute toxicity.
- Immunosuppressive effect
At the molecular level, these toxins disrupt normal cell function by inhibiting protein synthesis via binding to the ribosome and by activating critical cellular kinases involved in signal transduction related to proliferation, differentiation, and apoptosis.
What are the symptoms of aflatoxin and deoxynivalenol consumption in humans?
- Edema of the legs
- Abdominal pain
- Vomiting
- Palpable liver
- Liver necrosis - fatty accumulation in the liver cells
- At the molecular level, these toxins disrupt normal cell function by inhibiting protein synthesis via binding to the ribosome and by activating critical cellular kinases involved in signal transduction related to proliferation, differentiation, and apoptosis.
What is vomitoxin?
- Active compound characterized as a trichothecene
- Called vomitoxin because of observed emetic effect on swine.
- First isolated by Japanese workers in 1972 as ‘Rd-toxin’ from barley infected with Fusarium spp., and from northwestern Ohio corn infected with Fusarium spp. in 1973.
a.k.a. deoxynivalenol
Deoxynivalenol commonly contaminates cereal-based foods.
Baking/heating is effective against deoxynivalenol, thus it is usually not found in most finished products.
True or False?
False.
Baking/heating seems to have little effect on deoxynivalenol, thus it is usually found in most finished products.
a.k.a. vomitoxin
Commonly contaminates cereal-based foods.
Baking/heating seems to have little effect on deoxynivalenol, thus it is usually found in most finished products.
True or False?
True.
a.k.a. vomitoxin
Commonly contaminates cereal-based foods.
What are methods of mycotoxin detection?
- Gas Chromatography and High Powered Liquid Chromatography (quantification) coupled with Mass Spectroscopy (identification)
- (fluorescence and UV detection).
- Thin-layer chromatography
- Enzyme-linked immunosorbent assay
How is probable daily intake calculated?
- Combining the mycotoxin content and the food consumption data for adult population
How is the health risk characterization of each mycotoxin (% relevant TDI) calculated?
%TDI=(PDI/TDI) x 100
Ratio is of probable to total daily intake expressed as a percentage.
Food and Drug Administration (FDA) has established an advisory level of 1 ppm DON for bran, flour, and germ targeted for human consumption
Discuss tolerable intakes of mycotoxins. [6]
TDI = daily; TWI = weekly
- TWI for OTA: 120 ng/kg bw
- TDI for sum of T-2 and HT-2 toxins: 100 ng/kg bw
- TDI for ZEA: 250 ng/kg bw
- TDI for DON and their acetyls: 1000 ng/kg bw
- TDI for NIV: 1200 ng/kg bw
No tolerable intake levels have been set for aflatoxins!
Describe regulations on mycotoxins (i.e., spectrum of safety from all aspects of exposure). [5]
- Trade barriers can arise with regulations for stringent levels for mycotoxins in grains (HACCP integration).
- Farmers recommended to apply GAP (good agricultural practices) at farm level.
- Grain processors recommended to apply GMP during handling and storage and distribution.
- Wholesalers apply GSP (good storage practices) during storage.
- “Biocontrol” using bacteria, yeasts and atoxigenic strains to control infection process.
What causes ergotism?
Claviceps purpurea
What foods serve as ergot hosts?
Rye, triticale, wheat, durum, barley, oat, quack grass, crested wheat grass, brome grass, foxtail, rye grass, orchard grass, timothy, wild rye, and other grasses serve as ergot hosts.
Describe the life cycle of ergot.
- Ergots over-winter on the ground or are sown with seed
- Ergots germinate in spring
- Ascospores form in stromata
- Ascospores eject and spread by wind
- Ascospores infect the host during flowering
- Ovaries colonized by fungas from base upwards
- Honeydew exudes from infected florets (secondary spread)
- Ergots develop in the place of grain
What are the toxic or biologically active principles of ergot?
- Peptides of lysergic acid or isolysergic acids in cyclol form
- Biological activity of C. purpurea can be ascribed only to the lysergic acid alkaloids (e.g., ergotamine)
Describe the three major types of toxic effects from alkaloids of ergot.
- Peripheral effects, such as vasoconstriction and contraction of the uterus
- Neurohumoral effects; e.g., antagonism between epinephrine and serotonin
- CNS effects; e.g., the inhibition of the vasomotor activity of the brain and stimulation of the sympathetic structures of the brain (especially the hypothalamus)
Describe the clinical symptoms of gangrenous ergotism.
- Initial symptoms include: pain in the lumbar region, limbs, the calf, followed with mild vomiting.
- After few weeks, the foot and hands become swollen, inflamed and burning pains. The affected part becomes numb and painless.
- At this stage, grangrene sets in. The gangrenous part blackens, shrinks, dries up and may fall off.
What are the clinical symptoms of convulsive ergotism?
- Characterized by sudden, painful, convulsive seizures beginning with the fingers and toes and spreading to the arms and the rest of the body.
- Convulsions may be followed by coma for 6 to 8 hours or by drowsiness or giddiness.
- Sometimes blindness or deafness follows.
What is the difference between aflatoxin B1 and B2?
The dihydrofurofuran moiety is also toxic - reduction of this portion reduces activity (B1 vs B2).
- Bifuranocoumarins fused to a cyclopentanone (or a lactone in G1/2)
List enzymatic and non enzymatic protection against ROS.
