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Home , Aflatoxin B1, Patulin

Zearalenones are estrogen mimics, bind to estrogen receptors

Affect reproductive systems in mammals Precocious puberty in Puerto Rico in 1980s? High in maize diet Not acutely toxic but may cause reproductive disorders Livestock and humans affected Contaminated maize the most common source, but also barley and malt Occurs together with other Fusarium

No FDA regulation of zearalenones, but EU regulates , : Aspergillus and Penicillium

Highly toxic, widely distributed Aflatoxins first discovered in 1960

Associated with death of over 100,000 turkeys in England

‘Turkey X disease’, related to peanut meal feed contaminated with Aspergillus flavus

Symptoms reproduced by feeding turkeys pure A. flavus and A. flavus culture extracts, hence

Aflatoxins the most potent naturally occurring cause in all animals tested at very low doses

Closely monitored in food supply by USDA, only regulated in US food supply 5 ppb for human, 30 ppb for animal feed EU limit is 2 ppb Up to 400,000 µg/kg can occur in a single corn kernel! structure of

Aflatoxin B fluoresces blue Aflatoxin G fluoresces green ppb Aflatoxins Produced by four species of Aspergillus: A. flavus, A. parasiticus, A. nomius, A. pseudotamarii

Aflatoxins designated as B, G (blue or green fluorescence), and M (found in milk) Aflatoxin M is found in animal tissue, derived from aflatoxin B1

Aflatoxins found in: milk, cheese, meat, yogurt, eggs, corn, cottonseed meal, spices, peanuts, almonds, pecans, pistacios, brazil nuts, figs, various other foods

Aflatoxin in maize mainly associated with drought summer of 1998 maize in SE US had >150 ppb

Milk, eggs, meat can be contaminated from animals that consume contaminated feed Aflatoxin diseases Acute aflatoxicosis hepatitis, liver degeneration, ‘fatty liver syndrome’ Kwashiorkor, malnutrition disease (protein deficiency) in infants linked to seasonal occurrence of aflatoxins in food fatty liver, immunosuppression aflatoxins found in autopsies causal relationship unclear Reye’s syndrome acute encephalopathy, fatty degeneration of liver link to aflatoxin suspected but not clear relationship to aflatoxin exposure not consistent Chronic aflatoxicosis liver cancers aflatoxin linked to specific mutations (biomarkers) G to T transversions at a specific location (position 249) in tumor suppressor gene p53 finding these markers in tumors a direct link to aflatoxin also immunosuppressive 2012 summer drought increased aflatoxin levels in US maize Aspergillus contamination Ochratoxin-A

Aspergillus ochraceous, Penicillium verrucosum most frequently found mycotoxin in poultry meat and pork, sausages etc Also found in barley, green coffee beans, grapes, raisins

Nephrotoxic, associated with various kidney disorders Carcinogenic in mice

Conjecturally associated with ‘Balkan endemic nephropathy’ chronic kidney and excretory system problems/tumors linked to dietary Penicillium contamination

Airborne contamination by ochratoxin a high risk factor for workers grain dust etc building contamination, e.g. heating ducts

Not regulated by FDA, regulated by EU Stachybotrys

Sick Building syndrome

Stachybotrys is a cellulolytic , so can grow on cellulose based building materials, like wallboard, if water is available

Associated with water damage in buildings Stachybotrys a common soil fungus, also produces mycotoxins (Satratoxin H). Mycotoxins present in conidia

Stachybotrycosis: from inhalation of conidia? Association between disease and Stachybotrys in buildings not proved Stachybotrys chartarum a cellulolytic fungus S. chartarum produces a variety of macrocylic and related trichoverroids: roridin E and L-2; satratoxins F, G, and H; isosatratoxins F, G, and H; verrucarins B and J; and the trichoverroids, trichoverrols A and B and trichoverrins A and B. satratoxin G was the most cytotoxic of eight trichothecenes tested on mammalian cells, even more toxic than the well known T-2 associated with alimentary toxic aleukia. Other researchers have also reported the high toxicity of satratoxins compared to other trichothecenes (18). The LD50 in mice for satratoxins is ~1 mg/kg

In addition, the fungus produces nine phenylspirodrimanes (spirolactones and spirolactams) and cyclosporin, which are potent immunosuppressive agents Trichothecenes Stachybotrycosis

In Ukraine and other parts of eastern Europe during the 1930s outbreaks of a new disease in horses and other animals symptoms such as irritation of the mouth, throat, and nose; shock; dermal ; a decrease in leukocytes; hemorrhage; nervous disorder; and death. Similar to T-2 poisoning (alimentary toxic aleukia)

In 1938, Russian scientists determined the disease was associated with S. chartarum (then known as S. alternans) growing on the straw and grain fed to the animals.

Horses were fed cultures of the fungus. Contents from 30 petri plates containing the fungus were fed to horses and resulted in death, while even the contents of one plate resulted in sickness.

Horses seem to be especially susceptible to these ; 1 mg of pure toxin is reported to cause death. Most outbreaks were associated with hay or feed that became infested during storage under wet conditions. Stachybotricosis of horses due to consumption of contaminated hay Contaminated hay In 1996 workers at a horticultural facility in Germany developed very painful, inflamed lesions on their fingertips followed by scaling off of the skin when they handled decomposable pots infested with S. chartartum. The pots were made of recycled paper.

Pots made of recycled paper showing S. chartarum growing on the sides (notice the black blotches on the white pots). Photograph from Dill, et al., 1997. Mycoses 40:110-114. In indoor environments S. chartarum frequently linked to water damage.

Pithomyces chartarum causes facial eczema of sheep and cattle Toxin sporidesmin affects the liver Incomplete breakdown of chlorophyll by liver Photoreactive compounds in exposed skin lead to eczema symptoms Alternaria mycotoxins

Tenuazonic acid Alternariol Alternariol methyl ether

Tenuazonic acid found in carrots, tomatoes, apples, wheat, oats, barely, sorghum

Causes growth reduction in livestock Tenuazonic acid interferes with protein synthesis, associated with cancers also a phytotoxin, associated with pathogenicity to

Produced by Penicillium species associated with pome fruits P. expansum, also some Aspergillus species Carcinogenic? A concern in infant foods

Mushroom toxins Amanita phalloides, A. virosa Galerina autumnalis

Toxins are lethal in 2 - 8 days, LD50 0.5 mg/kg inhibit mammalian RNA polymerase II phallotoxins lethal in 2- 5 hr, but LD50 3 mg/kg not absorbed through gut virotoxins all are cyclic peptides

Amatoxins and phallotoxins are encoded by genes and are directly synthesized on ribosomes

Initially 34-35 amino acid pro- proteins

Post translational processing cleaves into 1 -10 residue structure

phallotoxin How much amatoxin is lethal?

LD50= 0.1mg/kg body weight, so 6 - 7 mg (60-70 kg adult) concentration of amatoxin in mushroom tissue 0.5 - 1.5 mg/g an average sized A. phalloides weighs 60 g (30 - 90 mg toxin per mushroom)

Concentration in Galerina spp. is less, and the mushrooms are smaller. About 100 - 150 g of mushrooms (~20) would be lethal symptoms: 1. 8-12 h after ingestion GI irritation, vomiting, diarrhea 2. 24 h after ingestion recovery, ‘honeymoon’ 3. 72 h after ingestion recurrence of abdominal symptoms and liver failure 4. Coma, death

Amanita muscaria A. pantherina

Ibotenic acid is converted to upon ingestion, and excreted in urine. Muscimol causes hallucinations and has been used recreationally and as a traditional ‘entheogen’. Ibotenic acid, muscimol affect neurotransmitters (GABA receptors) , may be neurotoxic

About 6 mg of muscimol (~1 mushroom) induces CNS effects Coprine, Coprinopsis atramentaria

Coprine, from C. atramentarius inhibits the aldehyde dehydrogenase which converts acetaldehyde to acetate. Buildup of acetealdehyde causes nausea.

Similar in action to sulfiram (antabuse), used to treat chronic alchoholism