1. Poisonous Plants, Fungi, and Algae
I - Poisonous and Toxic Fungi

2. Fungal Toxins
Mushroom Toxins
Mycotoxins

3. Mushroom Toxin Groups I - Amanitins (Cyclopeptides)
II - Gyromitrin (Monomethylhydrazine)
III – Orellanine
IV - Coprine
V - Muscarine
VI - Ibotenic acid and Muscimol - already discussed
VII - Psilocybin (psilocin) - already discussed
VIII - Gastrointestinal irritants

4. Mushroom Structure

5. Cellular Toxins I - Amanitins - Cyclopeptides
II - Gyromitrin - Monomethylhydrazine
III -Orellanine

6. Group I: Distrubution of Amanitins
Amanita bisporigera,
A. phalloides,
A. verna,
A. virosa
Galerina autumnalis,
G. marginata, etc
Lepiota spp.
Conocybe filaris

7. Destroying Angels A. virosa and A. verna

8. Amanita phalloides

9. Galerina autumnalis

10. Conocybe filaris

11. Phallotoxins (Phalloidins)
Cyclopeptides (amino acids in a ring)
Phallotoxins consist of 7 amino acids in a ring
Cause cell destruction in liver?
Attack plasma membrane - bind to protein receptors
Cells leak Ca++ and then K+
Toxin enters cytoplasm and attacks organelles by rupturing lysosome membrane
Evidence suggests these may not be lethal because it does not appear to be absorbed through the intestine in experimental animal studies

12. Amatoxins (Amanitins)
8 amino acids in a ring
Also cause cellular destruction
Attacks cells with high rates of mitosis
First attacks GI tract, produces lesions in stomach which cause initial symptoms - vomiting, severe diarrhea, pain
Toxin is then absorbed into blood and carried to liver where most of the damage occurs

13. Amatoxins in the Liver Toxin invades nucleus of liver cells
Destroys nucleolus and inhibits mRNA polymerase
Toxin circulates to kidneys and attack kidney cells then re-enter blood stream and back to liver
Amatoxins are LETHAL

14. General Structure of Amatoxin

15. Symptoms of Amatoxin Poisoning
Within 5 to 24 hours - diarrhea, vomiting, and pain (typically 6 to 12 hours)
Short remission and apparent improvement
4 to 11 days later
severe liver damage
acute kidney failure
coma and death

16. Treatment of Amatoxin Poisoning
No antidote
Supportive care - pump stomach, restore fluid balance
Activated charcoal to absorb toxins in stomach
Plasmapheresis
Liver transplant
Other treatments which may inhibit toxin uptake by hepatocytes
High dose penicillin G - one million units/kg on 1st day and 500,000 units for next two days
Silibinin - water soluble extract of milk thistle

17. Group II - Gyromitrin (Monomethylhydrazine)
Gyromitra brunnea,
G. caroliniana,
G. esculenta,
G. fastigata, G. infula, G. gigas
Helvella elastica, H. lacunosa
Paxina spp.
Sarcosphaera crassa

18. Morel False Morel Morchella Gyromitra

19. Gyromitrin Poisoning
Gyromitrin hydrolyzes to monomethylhydrazin (rocket fuel) which is highly toxic
Resembles Amanita poisoning but is less severe.
Latent period of hours after ingestion
Followed by sudden onset of abdominal discomfort (feeling of fullness), severe headache, vomiting, and sometimes diarrhea, pain, cramps
The toxin primarily affects the liver with additional disturbances to blood cells and the central nervous system - may result in loss of coordination, coma, convulsions

20. Group III - Orellanine
Distribution - Cortinarius orellanus, C. orellanoides, C. reainierensis
Long latent period of 3 to 14 days - attacking kidneys
Burning thirst, excessive urination - first symptoms
Followed by nausea, headache, muscular pains, chills, spasms, and loss of consciousness
In severe cases, kidney failure may result in death
Fatty degeneration of the liver and severe inflammatory changes in the intestine accompany the renal damage

21. Toxins Affecting Autonomic Nervous System
IV - Coprine
V - Muscarine

22. Group IV - Coprine Distribution
Coprinus atramentarius - inky cap
Possibly other Coprinus species
Coprinus micaceus
Coprinus fuscescens
Coprinus insignis
Coprinus spp. (some African species)
Clitocybe clavipes

23. Coprine Coprine interfers with breakdown of alcohol
Chemically this compound is very similar to Antabuse
Symptoms occur usually within 5 to 30 minutes after eating this mushroom, if alcohol has been ingested within the past 72 hours

24. Coprine Poisoning Hot and sweaty face, becoming flushed
Flushing spreading to the neck and chest
Rapid, difficult breathing,
Rapid heart rate
Violent headache
Nausea and vomiting
Lasts for hours

25. Group V - Muscarine Inocybe species Clitocybe species
Amanita muscaria and Amanita pantherina were previously thought to have contained primarily muscarine - but they contain insignificant amounts

26. Muscarine Poisoning
Characterized by increased salivation, perspiration, and lacrimation within 15 to 30 minutes after ingestion
With large doses, symptoms may be followed by abdominal pain, severe nausea, diarrhea, blurred vision, and labored breathing
Intoxication generally subsides within 2 hours
Deaths are rare, but may result from cardiac or respiratory failure in severe cases
Atropine is the antidote (only one with antidote)

27. Toxins Affecting the Central Nervous System
VI - Ibotenic Acid and Muscimol
VII - Psilocybin and Psilocin

28. Group VIII - Gastrointestinal Irritants
Large variety of mushrooms contain toxins that can cause gastrointestinal distress, including but not limited to nausea, vomiting, diarrhea, and abdominal cramps
Symptoms similar to those caused by the deadly protoplasmic poisons - but usually have a rapid onset
Some mushrooms may cause vomiting and/or diarrhea which lasts for several days

29. Chlorophyllum molybdites

30. Chlorophyllum molybdites

31. Mycotoxins

32. Mycotoxins Background Health effects
Carcinogenic
Immediate toxic effects
Immunosupression
History – Turkey X Disease – Aspergillus flavus

33. Aflatoxins Aflatoxin: A (aspergillus) - fla (flavus) - toxin
Four toxins soon identified: aflatoxin B1, B2, G1, G2 - (B and G refer to blue or green florescence under uv-light)
Today known to be 10 aflatoxins
Aflatoxin B1 most important - highly carcinogenic and widespread occurrence in foods

34. Sources of aflatoxins
Produced by 3 species of Aspergillus: A. flavus, A. parasiticus, A. nomius
Aspergillus flavus a common fungus that occurs on grains and legumes
A. parasiticus most toxigenic species
Aflatoxins not only toxic but also carcinogenic, mutagenic, and teratogenic

35. Aflatoxin B1 is Mutagenic
Hepatocellular carcinoma (HCC) is a major cause of mortality in certain areas of the world
About 50% of the HCC cases in parts of the world where food is contaminated with AFB1show a mutation in codon 249 of p53 tumor suppressor gene
Mutation consists of transversion of G->T in the third position of codon resulting in serine instead of arginine - lab studies confirm

36. Aflatoxin levels
Permissible limits generally quite low (15-20 parts per billion in US - lower in Europe) for human food
Some scientists feel that no detectable levels of aflatoxins should be permitted because of the carcinogenic effects

37. Other mycotoxins
Today over 400 mycotoxins have been identified from 150 species of fungi with new ones discovered each year
Ergot alkaloids now considered mycotoxins
Species of Aspergillus, Penicillium, Fusarium, Alternaria, Cladosporium and Stachybotrys form mycotoxins

38. Common toxigenic fungi
Aspergillus
Penicillium
Common toxigenic fungi
Stachybotrys
Fusarium

39. Ochratoxins
Produced by species of Aspergillus such as Aspergillus ochraceus
Most important is Penicillium verrucosum which occurs on grains
Ochratoxin A a nephrotoxin responsible for nephropathy in pigs and probably humans
It is immunosuppressive and also assumed to be carcinogenic in humans - in animal studies it is one of the strongest carcinogens

40. Patulin
Produced by a number of species of Penicillium, Aspergillus and Byssochlamys.
Most important producer is Penicillium expansum.
Fungus causes a soft rot of apples; toxin found in apple juice
Patulin first attracted attention as an antibiotic in 1943; no current interest in antibiotic properties because it is too toxic

41. Trichothecenes Produced by several species of Fusarium
One of the most toxic is T-2
Believed T-2 responsible for outbreak of alimentary toxic aleukia (ATA) in Siberia during and after World War II
In some areas 10% of the population developed the disease and in most cases it was fatal

42. Alimentary Toxic Aleukia - ATA
Characterized by nausea, vomiting, hemorrhages in many organs, bleeding from nose and throat, bloody diarrhea, low leukocyte count, exhaustion of bone marrow
About a third of deaths due to strangulation from internal swelling of throat
Years later scientists made the connection between the disease and consumption of moldy grain
Symptoms appeared when people ate 2 kg of moldy grain, 6 kg was lethal. Similar hemorrhagic syndrome in animals called moldy corn toxicosis

43. Vomitoxin (Deoxynivalenol)
A trichothecene produced by some Fusarium spp.
Produces vomiting in pigs at low concentrations
Much less toxic than T-2 but immunosuppressive
Contaminates corn, barley, and wheat
Permissible limits are 0.3 ppm for flour and 0.1 ppm in bread or breakfast cereal
During recent wet growing season, Ontario farmers lost $17 million on a wheat harvest contaminated with vomitoxin.

44. Macrocyclic trichothecenes
More toxic than T-2
Produced by Stachybotrys chartarum (S. atra) and also by species of Myrothecium
Specific toxins are satratoxins, verrucarins, and roridins
Responsible for the deaths of many horses, but it can also affect cattle, pigs, sheep, poultry
Complex of unpleasant symptoms like ATA.
Stachybotrys found indoors in many locations growing on ceiling tiles and wallboard
Concern about airborne inhalation of spores

45. Yellow rain
During the Vietnam war, there was concern that the Viet Cong were using chemical weapons against the US as well as the population in Laos and Cambodia
Victims were sprayed with a yellow rain
Symptoms were like ATA (possibly some evidence of trichothecene toxins in some of the victims. However, the issue was not clear cut)
Little evidence Viet Cong using chemical weapons
Samples of the yellow rain deposits later shown to be largely made up of pollen - “cleansing flight theory”
This issue has never been resolved

46. Exposure in Contaminated Environments
In contaminated indoor environments, people may be inhaling hundreds to thousands of fungal spores per hour
If the spore are toxigenic, risks may occur
Many different types of fungi occur indoors
Most common genus is Cladosporium - just like it is outdoors
Penicillium and Aspergillus often exist at higher concentrations indoors
Stachybotrys has received most media attention over the past 9 years

47. Stachybotrys Soil fungus in nature
Commonly found indoors on wet materials containing cellulose, such as wallboard, jute, wicker, straw baskets, and paper materials
Spores in slimy mass
Thought to be allergenic although little is known
May produce potent mycotoxins

48. Stachybotrys

51. Health effects from airborne exposure?
Clinical studies not completed yet
Possible correlations in contaminated buildings but no experimental studies with human exposure
Animal studies suggest effects of respiratory exposure may be important but may not correlate with exposure levels
Possible effects: immune suppression, rash, headache, fatigue, sore throat, pulmonary hemorrhage (in infants)
We need more research