Poisonous Plants, Fungi, and Algae

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Poisonous Plants, Fungi, and Algae

• II Mycotoxins

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Fungal toxins

• Fungi produce a tremendous diversity of toxic
  compounds
• Mushroom toxins formed in the fleshy fruiting
  bodies of higher fungi
• Mycotoxins formed by hyphae of common molds
  growing under a variety of conditions

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Mycotoxins

• Mycotoxins produced by many fungi growing in
  contaminated foods and other substrates.
• Generally, the highest levels in substrates with
  high water activity and warm temperatures.
• Can develop in grains or nuts in the field due to
  activities of pathogenic as well as saprobic
  fungi on the living plant
• Forage grass may contain mycotoxins because of a
  pathogenic fungus or a fungal endophyte

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Mycotoxins

• More commonly -- mycotoxins develop in storage
  and remain within the food after processing and
  cooking
• Many common indoor environmental contaminants are
  toxigenic - able to produce toxins
• Some studies revealed significant levels of
  airborne mycotoxins in occupational settings,
  offices, and even homes

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Health effects of mycotoxins

• Acute and chronic effects on both humans and
  livestock
• Mycotoxins are believed to be among the most
  potent known carcinogens
• Majority of research focused on health effects
  following ingestion of contaminated food
• Effect range from immediate toxic responses and
  immunosupression to potential long-term
  teratogenic, estrogenic, and carcinogenic
  effects.
• Possible health effects due to airborne exposure
  (exposure to airborne spores with mycotoxins)

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History of mycotoxins

• Turkey X disease killed over 100,000 young
  turkeys in 1960 in England
• Affected turkeys stopped eating, became
  lethargic, suffered hemorrhages under the skin,
  and died
• Autopsies showed livers had undergone extensive
  necrosis, kidneys developed lesions
• Partridges, pheasants, ducklings, and other
  animals also affected
• Only factor in common with all the cases was
  Brazilian peanut meal as a feed supplement.
• Toxin isolated from feed associated with fungal
  contaminant Aspergillus flavus

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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

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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

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Effects of aflatoxins

• Toxic effects clearly shown in India in 1974 when
  hundreds were poisoned by eating corn containing
  aflatoxins and 106 people died
• Even when levels not toxic, prolonged exposure
  caused liver cancer in every species of lab
  animal tested
• Believed responsible for high rates of liver
  cancer in population groups in Asia and Africa
  where contaminated food is often consumed
• Most important crops - peanuts and corn

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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-gtT in the
  third position of codon resulting in serine
  instead of arginine - lab studies confirm

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Aflatoxins in corn

• Contamination occurs both in the field before
  harvest and in storage
• Most researchers agree is that if the
  contamination is prevented before harvest the
  problem can be managed
• Emphasis is placed on preventing A flavus
  infections of the corn by developing disease
  resistant varieties and also by insect control to
  prevent initial infections at wound sites

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Aflatoxin levels

• Levels permissible in foods subject to legal
  limits in many countries
• Today, foods most frequently contaminated,
  routinely screened before processing or sale
• 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

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Economic impact

• Because of enforced limits the presence of
  aflatoxins can have serious economic implications
• In 1980 nearly 66 of random corn samples from
  North Carolina had concentrations exceeding 20
  ppb resulting in a 31 million loss to producers
  and handlers
• When cows and goats are fed grains contaminated
  with aflatoxins, they produce milk with
  aflatoxins - as a result, limits exist for
  livestock feed but not as low

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Average yearly level of aflatoxin contamination
from corn grown along the coastal plain of Georgia
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Economics and health

• In US most corn goes to animal feed so aflatoxin
  exposure are not as much of a problem as in other
  countries
• In many countries in Africa, Central and South
  America and Mexico corn is a primary staple for
  human food and many people are exposed to
  aflatoxin levels above the standard
• In Benin - mean levels 37 ppb
• In Nigeria - mean levels 292 ppb

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Aflatoxin production

• Aflatoxins are produced under certain conditions
  but only by some strains
• Nontoxigenic strains of A. flavus used to prepare
  fermented foods in the orient

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Other mycotoxins

• Today over 400 mycotoxins have been identified
  from 150 species of fungi with new ones
  discovered each year
• Species of Aspergillus, Penicillium, Fusarium,
  Alternaria, Cladosporium and Stachybotrys form
  mycotoxins

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Mycotoxin production

• Can occur in one strain of a species, other
  strains of the same species not toxigenic
• Fungi from air samples in homes tested for
  mycotoxin production using tissue culture of
  human fibroblast cells
• In multiple isolates of a single species (up to
  12) some produced mycotoxins, others did not
• Warm temperatures and abundant moisture promote
  mycotoxin production

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Common toxigenic fungi
Aspergillus
Penicillium
Stachybotrys
Fusarium
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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

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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

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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

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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

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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.

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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
• Fungi are cellulose decomposers and found growing
  on hay or straw stored under poor conditions.

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Macrocyclic trichothecenes

• 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

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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

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Zearalenone

• Produced by species of Fusarium found in moldy
  corn
• Chronic exposure is estrogenic
• Female pigs especially sensitive causing
  vulvovaginitis.
• Swelling of the vulva, enlargement of the mammary
  glands, enlargement of the uterus, and vaginal
  prolapse.
• In lower levels causes infertility, stillbirths,
  and small litters

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Fumonisins

• Produced by several Fusarium species on moldy
  corn possibly other fungi as well
• First discovered in 1988
• Implicated in cases of esophageal cancer in
  humans and other cancer in farm animals
• Shown to disrupt sphingolipid metabolism
  (involved in membrane structure)
• Implicated in birth defects relating to neural
  tube abnormalities

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Exposure in Contaminated Environments

• Beginning in late 1980s scientists began raising
  the issue of possible inhalant exposure
• Mycotoxins are not volatile but they are present
  in fungal spores
• In contaminated indoor environments, people may
  be inhaling hundreds to thousands of fungal
  spores per hour
• If the spore are toxigenic, risks may occur

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Indoor Fungi

• Indoor spores generally reflects outdoors unless
  there is a source of contamination
• Many different types of fungi occur
• Most common genus is Cladosporium - just like it
  is outdoors
• BUT Penicillium and Aspergillus often exist at
  higher concentrations indoors
• Stachybotrys has received most media attention
  over the past 4 years

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Cladosporium

• Common fungal genus occurring both indoors and
  outdoors
• Most abundant outdoor spore type with a worldwide
  distribution
• Normally exists as a saprobe or weak plant
  pathogen
• Spores are known to be allergenic

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Cladosporium on diffuser
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Penicillium

• One of the most common soil fungi in natural
  environment
• Over 250 species
• Well known allergen
• Some species produce mycotoxins
• Produce VOCs

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Penicillium in culture
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Aspergillus

• Also common soil fungus and cause rot of stored
  grain
• Over 150 species
• Well known allergens
• Several species form mycotoxins
• Some species can grow at high temperatures
• Several species can cause human infections of
  lung and hypersensitivity pneumonitis

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Penicillium and Aspergillus

• Small spores passively aerosolized when spore
  clusters disturbed
• Spores extremely buoyant, remain airborne for
  extended time

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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

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Stachybotrys
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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 important
• Possible effects immune suppression, rash,
  headache, fatigue, sore throat, pulmonary
  hemorrhage (in infants)
• We need more research