MYCOTOXICOSIS AND

MYCETISMUS
 4.FUMONISINS
 The fumonisins are a group of mycotoxins derived from Fusarium and their Liseola section.They have
strong structural similarity to sphinganine, the backbone precursor of sphingolipids.

 More specifically, it can refer to:

 Fumonisin B1
 Fumonisin B2
 Fumonisin B3
 Fumonisin B4

 As the fumonisins appear to be non-genotoxic the possibility that they belong to another class of non-
genotoxic carcinogens, the peroxisome proliferators, was investigated
 Genetic engineering is reported as a promising means of detoxifying
mycotoxins. This approach may provide innovative solutions to the
problem of fumonisin in corn.

 At least 15 different fumonisins have so far been reported and other minor
metabolites have been identified, although most of them have not been
shown to occur naturally.
 In 2015, a unique class of non-aminated fumonisins was reported on
grapes infected with Aspergillus welwitschiae, although their toxicities
have not yet been established.
 cute intoxication with fumonisins causes diarrhoea and abdominal
pain and their chronic exposure is correlated with oesophageal
cancer in humans.
 Several studies have pointed out that high levels of FB1 in corn are
related with high incidence of oesophageal cancer in the population
of the same regions.
 4.OCHRATOXINS
 are a group of mycotoxins produced by Penicillium verrucosum and different species of
Aspergillus molds (A. alliaceus, A. auricomus, A. carbonarius, A. glaucus, A. melleus, A.
niger) that contaminate crops in the field leading to field and storage ochratoxins
contamination (Bennett and Klich 2003).
 Ochratoxins are derivatives of an isocoumarin moiety linked to phenylalanine by an amide
bond. The most important ochratoxins are ochratoxin A (OTA), ochratoxin B (OTB),
ochratoxin C (OTC), and ochratoxin α (OTα) . The most frequently found and the most
toxic is OTA.
 Ochratoxins occur worldwide, but most data are from European countries . Ochratoxins contaminate
cereals (barley, maize, oats, rice, rye, wheat) and other plant products (coffee beans, nuts, dried
peanuts, spices, dried fruits, raisins, wine, grape juice, and beer). Through a carryover effect, they
might be found as residues in food of animal origin (pork and poultry meat, milk, cheese) which
may contribute to human exposure. Inhalation in the workplace is a possible route of exposure .
Ochratoxins are relatively heat stable; baking and roasting reduces the content by 20%, while
boiling has no effect.
Toxic effects
 Ochratoxin A (OA), the most toxic member (LD50 about 20–25 mg kg−1)
and also most commonly found toxin in this group, is a potent nephrotoxin
causing kidney damage, including degeneration of the proximal tubule, in
many animal species.
 Liver necrosis and enteritis were also observed. Other than acute toxic
effects, OA also acts as an immunosuppressor and teratogen. Although OA
has never been shown to be mutagenic, a weak genotoxic effect has been
demonstrated in several systems.
 Ochratoxin A is only a weak nephrocarcinogen because a high level of toxin
and an extended period of exposure are necessary to induce the tumor.
 Humans are exposed via the diet. Cereals and grain products are the main
sources; however, ochratoxins are found in animal tissues with the highest
residues in the kidneys.
 Thus, meat products such as sausages, bacon, or ham also contribute to
exposure. Human exposure is particularly high within, but not limited to,
the Balkans and northern Europe.
 Ochratoxin A residues have been found in human serum, plasma, and milk
from northern European countries, particularly Denmark and Germany, and
from Canada.
5.PATULIN

 Patulin is an organic compound classified as a polyketide. It is a white

powder soluble in acidic water and in organic solvents.
 It is a lactone that is heat-stable, so it is not destroyed by pasteurization or
thermal denaturation. However, stability following fermentation is lessened.
It is a mycotoxin produced by a variety of molds, in particular, Aspergillus
and Penicillium and Byssochlamys. Most commonly found in rotting apples,
the amount of patulin in apple products is generally viewed as a measure of
the quality of the apples used in production.
 Patulin has been found in other foods such as grains, fruits, and vegetables.
 Frequently, patulin is found in apples and apple products such as juices,
jams, and ciders. It has also been detected in other fruits including cherries,
blueberries, plums, bananas, strawberries, and grapes.[5] Fungal growth
leading to patulin production is most common on damaged fruits.[8] Patulin
has also been detected in grains like barley, wheat, corn and their processed
products as well as in shellfish.[5][9] Dietary intake of patulin from apple juice
has been estimated at between 0.03 and 0.26 μg/kg bw/day in various age
groups and populations.[10] Content of patulin in apple juice is estimated to be
less than 10–15μg/L
 While not a particularly potent toxin, patulin is genotoxic. Some theorize that
it may be a carcinogen, although animal studies have remained inconclusive.
Patulin has shown antimicrobial properties against some
microorganisms.Several countries have instituted patulin restrictions in apple
products. The World Health Organization recommends a maximum
concentration of 50 µg/L in apple juice
 In humans, it was tested as an antiviral intranasally for use against the
common cold with few significant adverse effects, yet also had negligible or
no beneficial effect.
7.TRICHOTHECENES
 Trichothecenes toxins (TCT) are produced by several fungal genera;
however, most of them have been isolated from Fusarium spp. TCT have
been found to contaminate wheat, barley, corn, rice, rye, oats, and other
crops. The effect of TCT has been extensively studied on poultry and farm
animals as TCT contaminate feed to a large extent
 Epoxides are found in all TCT at the C12 and C13 positions (Fig. 12.5C),
which is responsible for its toxic activity. TCT affect cell division in the
body, where cells are actively dividing such as the skin, gastrointestinal
tract, lymphoid, and erythroid cells. In these cells, TCT inhibit the protein
synthesis, resulting in acute necrosis in mucosal lining and skin. More fatal
consequences are depressed immune function and reduced bone marrow
 Symptoms may occur among exposed humans or animals. The likelihood of
developing adverse effects following exposure depends on such variables
as: toxin type and purity, dose, and duration of exposure. Dermal exposure
in some situations could lead to burning pain, redness, and blisters, and oral
exposure may lead to vomiting and diarrhea.
 Ocular exposure might result in blurred vision, and inhalational exposure
might cause nasal irritation and cough. Systemic symptoms can develop
with all routes of exposure (especially inhalation) and might include
weakness, ataxia, hypotension, coagulopathy, and death
8.ZEARALENONE

 Zearalenone is a nonsteroidal estrogenic mycotoxin produced by several

species of Fusarium fungi. The primary producer of zearalenone is
Fusarium graminearum (teleomorph Gibberella zeae). Additional Fusarium
fungi capable of producing zearalenone include F. culmorum, F.
verticillioides (F. moniliforme), F. sporotrichioides, F. semitectum, F.
equiseti, and F. oxysporum.
 Contamination of cereal grains by zearalenone has been reported worldwide,
primarily in temperate climates. Typically, zearalenone concentrations are
low in grain contaminated in the field, but increase under storage conditions
with moisture greater than 30%–40%. Zearalenone has major effects on
reproduction in females (as evidenced by hyperestrogenism), but it affects
the male reproductive system as well
 Zearalenone (ZEN) is very often found in grains, but also a huge range of
other commodities as soybeans can be contaminated. ZEN has limited, but
due to its oestrogen-like activity it can disrupt steroid hormone functions
when being consumed in sufficient levels. This might lead to hyper-
oestrogenism in humans.
 Precocious pubertal changes in young children have been reported in
Puerto Rico and gynecomastia with testicular atrophy in rural males in
southern Africa.
 Cases of premature breast development in girls under 8 years of age related
to ZEN-contaminated food intake were reported in Hungary and Italy.
 MYCETISMUS
 Mushroom poisoning is poisoning resulting from the ingestion of mushrooms that contain
toxic substances. Symptoms can vary from slight gastrointestinal discomfort to death in
about 10 days. Mushroom toxins are secondary metabolites produced by the fungus.
 Mushroom poisoning is usually the result of ingestion of wild mushrooms after
misidentification of a toxic mushroom as an edible species.
 The most common reason for this misidentification is a close resemblance in terms of colour
and general morphology of the toxic mushrooms species with edible species.
 The safety of eating wild mushrooms may depend on methods of preparation for cooking.
Some toxins, such as amatoxins, are thermostable and mushrooms containing such toxins
will not be rendered safe to eat by cooking.
1.COPRINE POISONING
 Coprine is a mycotoxin. It was first isolated from common inkcap (Coprinopsis
atramentaria). It occurs in mushrooms in the genera Coprinopsis. When combined with
alcohol, it causes "Coprinus syndrome". It inhibits the enzyme
acetaldehyde dehydrogenase, which is involved in the metabolism of alcohol. This
inhibition leads to a buildup of acetaldehyde, causing an alcohol flush reaction.
 Coprine hydrolyzes to glutamic acid and 1-aminocyclopropanol, which inhibits the
enzyme acetaldehyde dehydrogenase. 1-aminocyclopropanol quickly converts to
cyclopropanone hydrate, which binds covalently to the thiol group present in the enzyme,
deactivating the dehydrogenase activity.
 This inhibition then causes a buildup of acetaldehyde if ethanol is ingested. Since
acetaldehyde is toxic and can no longer be metabolized to the less toxic acetic acid, the
characteristic symptoms of coprine poisoning occur.
 Symptomes

 Symptoms of coprine poisoning include facial reddening/flushing, nausea, vomiting,

malaise, agitation, palpitations, tingling in limbs, and sometimes headache and excessive
salivation.
 This can be described as the alcohol flush reaction. Symptoms typically arise five to ten
minutes after consumption of alcohol. If no more alcohol is consumed, the symptoms
will generally subside over two to three hours, and symptom severity is proportional to
the amount of alcohol consumed.

 Consumption of alcohol can induce these symptoms for up to 5 days after ingesting
coprine. Interestingly, symptoms of coprine poisoning do not appear when the mushroom
is ingested raw, but only when the mushroom is cooked.
2.CYCLOPEPTIDES

 Cyclopeptides toxins represents family of nine cyclic octapeptides and produce

cellular necrosis through inhibition of mRNA systhesise by blocking specific enzyme
RNA polymerase 2 thereby interrupting protein synthesise and consequently causing
death of humans being consuming such toxins.
 α-Amanitin (alpha-Amanitin) is a cyclic peptide of eight amino acids. It is possibly the
most deadly of all the amatoxins, toxins found in several species of the mushroom genus
Amanita, one being the death cap (Amanita phalloides) as well as the destroying angel, a
complex of similar species, principally A. virosa and A. bisporigera. It is also found in the
mushrooms Galerina marginata and Conocybe filaris. The oral LD50 of amanitin is
100 μg/kg for rats.

 Unlike most cyclic peptides, amatoxins (and phallotoxins) are synthesized on ribosomes.
The genes encoding the proprotein for α-amanitin belong to the same family as those that
encode for phallacidin (a phallotoxin).
 α-Amanitin has an unusually strong and specific attraction to the enzyme RNA
polymerase II. Upon ingestion and uptake by liver cells, it binds to the RNA polymerase
II enzyme, effectively causing cytolysis of hepatocytes (liver cells).
 Few effects are reported within 10 hours; it is not unusual for significant effects to take as
long as 24 hours after ingestion to appear, with this delay in symptoms making α-amanitin
poisoning even more difficult to diagnose and all the more dangerous. By then, it is far
past the time in which stomach pumping would yield an efficient result.
 Diarrhea and cramps are the first symptoms, but those pass, giving a false sign of
remission. Typically, on the 4th to 5th day, the toxin starts to have severe effects on the
liver and kidneys, leading to total system failure in both. Death usually takes place around
a week from ingestion.
MUSCARINE POISONING
 Muscarine, L-(+)-muscarine, or muscarin is a natural product found in certain mushrooms,
particularly in Inocybe and Clitocybe species, such as the deadly C. dealbata.
 Mushrooms in the genera Entoloma and Mycena have also been found to contain levels of
muscarine which can be dangerous if ingested. Muscarine has been found in harmless trace
amounts in Boletus, Hygrocybe, Lactarius and Russula. Trace concentrations of muscarine
are also found in Amanita muscaria, though the pharmacologically more relevant compound
from this mushroom is the Z-drug-like alkaloid muscimol.
 A. muscaria fruitbodies contain a variable dose of muscarine, usually around 0.0003% fresh
weight. This is very low and toxicity symptoms occur very rarely. Inocybe and Clitocybe
contain muscarine concentrations up to 1.6%.

 Muscarine is a selective agonist of the muscarinic acetylcholine receptors.

 The name muscarine derives from that of Amanita muscaria, from which it was first isolated, by
German chemists Oswald Schmiedeberg and Richard Koppe at the University of Tartu, who reported
their findings in 1869. The mushroom's specific name in turn comes from the Latin musca for fly
because the mushroom was often used to attract and catch flies, hence its common name, "fly
agaric".
 Muscarine mimics the action of the neurotransmitter acetylcholine by agonising muscarinic
acetylcholine receptors. These receptors were named after muscarine, to differentiate them from the
other acetylcholine receptors (nicotinic receptors), which are comparatively unresponsive to
muscarine.
 There are five different types of muscarinic receptors: M1, M2, M3, M4 and M5. Most tissues
express a mixture of subtypes. The M2 and M3 subtypes mediate muscarinic responses at peripheral
autonomic tissues. M1 and M4 subtypes are more abundant in brain and autonomic ganglia. The odd
numbered receptors, M1, M3 and M5, interact with Gq proteins to stimulate phosphoinositide
hydrolysis and the release of intracellular calcium.
 Conversely, the even numbered receptors, M2 and M4, interact with Gi proteins to inhibit adenylyl
cyclase, which results in a decrease of intracellular concentration of cyclic adenosine monophosphate
(cAMP)
 Muscarine poisoning is characterized by miosis, blurred vision, increased salivation, excessive
sweating, lacrimation, bronchial secretions, bronchoconstriction, bradycardia, abdominal cramping,
increased gastric acid secretion, diarrhea and polyuria. If muscarine reaches the brain it can cause
tremor, convulsions and hypothermia.
 Cardiac ventricles contain muscarinic receptors that mediate a decrease in the force of contractions
leading to a lower blood pressure. If muscarine is administered intravenously, muscarine can trigger
acute circulatory failure with cardiac arrest.
 The symptoms of intoxication with mushrooms rich in muscarine, especially Inocybe, are very
typical: The symptoms start early, after one-quarter to two hours, with headache, nausea, vomiting, and
constriction of the pharynx. Then salivation, lacrimation, and diffuse perspiration set in, combined
with miosis, disturbed accommodation, and reduced vision. Gastric and small bowel colic leads to
diarrhea, and there is a painful urge for urination.
 Bronchoconstriction leads to asthmatic attacks and severe dyspnea, and bradycardia combined with
marked hypotension and vasodilation results in circulatory shock. Death after 8 to 9 hours has been
reported in about 5% of the cases, but can be avoided completely by prompt administration of IV or
IM anticholinergic drugs.[21]
4.ORELLANUS SYNDROME

 The Orellanus syndrome is a rare nephrotoxic disease caused by several fungi of the genus
Cortinarius. For a long time the sole report of this syndrome was a mass intoxication in
Poland.
 About 32 cases of Orellanus syndrome caused by Cortinarius orellanus, speciocissimus and
splendens have been described in recent years. A few other species are also suspected of
being nephrotoxic.
 The syndrome is characterized by a delayed latency period of 2 days to 3 weeks, and a
chronic evolution involving fatigue, anorexia, headache, thirst, pains in the lumbar region
and renal insufficiency with oliguria and anuria, and the clinical picture by reversible or
irreversible interstitial nephritis
Physiological methods like
 TLC
 GLC
 HPLC
 Spectrophotometry
 ELISA
Cytological assays can also done which can beperformed by producing cytotoxic effects on
the tissue culture( Primary foetal bovine kidney cells are
Used)
 Newer techniques ; DNA-DNA homology ,RFLP
Treatment
 Intravenous fluid replacement
 Hemodialysis and hemoperfusion
 Intravenous Penicillin and Silibinin (For amantoxin poisonings)
 Plasma exchange
 Atropine( For treatment of mycetismus)
 Corticosteroides
Prevention
 Reducing environmental pollution
 Applying appropriate technology control measures in food and feed production,
manufacturing, processing, preparation, packing and transport eg. Mushrooms.
Control measures
Decontamination: Investigation and removal of mycotoxins from feeds
 Hand picking and density segregation with water or NaCl for groundnut ,maize ,wheat
and rice reducing about 70 to90% mycotoxins.
Detoxification
Physical(use of heat in combination with pressure durin processing),
chemical (Formaldehide and ammonium hydroxide treatment)and microbiological method
 Add toxin binding agent to animal and human feeds.
Legislation: Food safty and Standards Authority of india(FSSAI) reviced the maximum permissible
levels of mycotoxins in various foods to protect the consumers health.