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The Major Groups Of Mycotoxins Causing Human And Animal Illness

The Major Groups Of Mycotoxins Causing Human And Animal Illness

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The Major Groups Of Mycotoxins Causing Human And Animal Illness

The Major Groups Of Mycotoxins Causing Human And Animal Illness

Groups Of Mycotoxins Causing Human And Animal Illness

Aflatoxins

Aflatoxins are a group of structurally related, toxic, secondary metabolites produced mainly by A. flavus and A.

parasitics that are present normally in soil and various organic materials.

While A. flavus strains produce only aflatoxins B1 (AFB1) and B2 (AFB2), A. parasiticus strains can produce AFB1,

AFB2, G1 (AFG1), and G2 (AFG2).

Since the discovery of AFs as causative agents of Turkey X disease killing 100,000 young turkeys in Great Britain in

1960, AFs have been the subject of a great deal of research and are considered the most studied mycotoxins.

The first outbreak of aflatoxicosis affecting humans, reported in India, led to the death of 100 people. Aflatoxin-

producing fungi grow on a wide variety of foods such cereals (maize, rice, barley, oats, and sorghum), peanuts,

groundnuts, pistachio nuts, almonds, walnuts, and cottonseeds.

Milk can be also contaminated with aflatoxin M1 (AFM1), which is a principal hydroxylated-AFB1 metabolite

biotransformed by hepatic microsomal cytochrome P450 in cows fed a diet contaminated with AFB1. AFM1 can be

detected in milk 12–24 h after cow consuming feed contaminated with AFB1, and the concentration of AFM1 in milk

is correlated to the levels of AFB1 in the raw feedstuffs.

The Major Groups Of Mycotoxins Causing Human And Animal Illness

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AFM1 can be detected also in some dairy products such as cheese with a concentration higher than that of

the raw milk since AFM1 is heat stable, binds well to casein, and is not affected by the cheese-making process  

AFs have carcinogenic, teratogenic, hepatotoxic, mutagenic, and immunosuppressive effects, with the liver the main

organ affected.

AFs are associated with both acute toxicity and chronic carcinogenicity in human and animal populations.

AFB1 is classified by the International Agency of Research on Cancer (IARC) as a Group 1 carcinogen,

with high risks for hepatocellular carcinoma (HCC) in individuals exposed to aflatoxins, while AFM1 is listed in

Group 2B (possibly carcinogenic to humans).

Acute toxicosis, while usually rare in developed countries, is common in some developing countries, especially in

Africa, whereas chronic carcinogenicity is a global problem.

The LD50 values range between 0.5–10 mg/kg body weight in different animal species. In humans, acute

aflatoxicosis is characterized by vomiting, abdominal pain, pulmonary and cerebral edema, coma, convulsions, and

even death.

In animals, symptoms of gastrointestinal dysfunction, reduced reproduction, reduced feed conversion and efficiency,

lowered milk and egg production, and anemia have been reported.

The toxic effects of AFB1 are principally due to the binding of bioactivated AFB1-8,9-epoxide to cellular

macromolecules, particularly mitochondrial and nuclear nucleic acids, and nucleoproteins resulting in general

cytotoxic effects.

Due to the extreme concerns about AF contamination in food and feed and their negative public health and economic

impacts, AFs have been closely controlled by the FDA since 1969.

Among all mycotoxins, AFs are the only ones regulated by established FDA action levels; others are subject only to

advisory levels. (Magnoli et al;2007)

The Major Groups Of Mycotoxins Causing Human And Animal Illness

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Ochratoxins

Discovered in 1965 in South Africa, ochratoxins are a group of related compounds produced by Aspergillus

ochraceus, Penicillium verrucosum, and other Penicilliumspecies.

The most important toxin of the group is ochratoxin A (OTA). Generally, P. verrucosum can produce OTA under

cool-temperate conditions, whereas A. ochraceus prefers to grow in hot-tropical regions Ochratoxins have been

found in a wide variety of agricultural commodities such as corn, wheat, barley, flour, coffee, rice, oats, rye, beans,

peas, and mixed feeds, and are notably present in wine, grape juice, and dried vine fruits.

Ochratoxins can also contaminate animal-derived products, such as meat and milk, and can be found in human milk.

Among all potential sources of OTA, coffees and wines are identified as major contributors to OTA intake.

Importantly, OTA is very stable in acidic environments and can tolerate high thermal processing; thus, OTA can be

found in cereal products, beer, and roasted coffee and is difficult to eliminate from food under normal cooking

conditions OTA is classified by IARC in Group 2B (possible human carcinogen), and it has been suspected to cause

Balkan Endemic Nephropathy (BEN: chronic tubulointerstitial disease) which affects south-eastern Europeans OTA

is acutely nephrotoxic and hepatotoxic. The oral LD50 of OTA ranges from 3 to 20 mg/kg in different animals.

In addition, OTA is reported to cause immunotoxicity, genotoxicity, neurotoxicity, teratogenicity, and embryotoxicity

in both humans and animals. OTA impacts the productivity of food-producing animals by reduced feed conversion

and body weight gain and may decrease egg production in laying hens. As OTA is fat-soluble, it tends to accumulate

in the tissue of animals, especially pigs.

Because of its structural similarity to the essential amino acid phenylalanine, OTA interferes with phenylalanine

hydroxylase activity in the kidney and liver, resulting in the inhibition of proper protein synthesis.

However, OTA also inhibits RNA and DNA synthesis. Until now, the US FDA has not set any

regulatory guidelines for OTA. However, the EU has established limits of OTA in several foodstuffs, in the ranges of

5–50 parts per billion (ppb) (Regulations (EC) No. 1881/2006). (Duarte;2000).

The Major Groups Of Mycotoxins Causing Human And Animal Illness

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Zearalenone

Zearalenone (ZEA), a macrocyclic β-resorcyclic acid lactone, is produced by Fusarium species, mainly F.

graminearum and F. semitectum .

Due to its structural similarity to the naturally-occurring estrogens, ZEA is better described as an estrogenic

mycotoxin that induces obvious estrogenic effects in humans and animals.

ZEA is frequently found in corn, wheat, barley, sorghum, and rye. Corn and wheat are more frequently contaminated

with ZEA in the United States and Canada, whereas, the major sources of ZEA contamination are wheat, rye, and

oats in European countries.

ZEA production is favored by high humidity and low-temperature conditions. ZEA contamination simultaneously

occurs with DON, and less frequently with aflatoxins.

ZEA is stable under regular cooking temperatures and partially eliminated under high temperatures.

ZEA is classified as a Group 3 carcinogen by IARC. Public health concern over ZEA is associated with its strong

estrogenic activity.

ZEA binds competitively to estrogen receptors (ERα and ERβ) in a number of in vitro or in vivo models in various

animal species, resulting in changes and lesions in the female reproductive system.

ZEA and its derivatives act by displacing estradiol from its uterine binding protein, eliciting an estrogenic response.

ZEA causes significant alterations in the reproductive tract of laboratory and domestic animals. Infertility swelling of

the uterus and vulva increased embryo lethal resorptions, and atrophy of ovaries have been observed in mice, rats,

guinea pigs, and rabbits.

In cattle, consuming feed contaminated with a high amount of ZEA may be directly associated with

infertility, reduced milk production, and hyperestrogenism.

To date, there are no advisory levels of ZEA set by the US FDA. However, the European Commission has regulated

the maximum levels of zearalenone ranging between 20–100 ppb in various food commodities ((EC) No.

1126/2007)

The Major Groups Of Mycotoxins Causing Human And Animal Illness

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Fumonisins

Fumonisins, a group of non-fluorescent mycotoxins, were discovered in 1988.  These are hydrophilic

mycotoxins that are structurally different from most other mycotoxins, which can be dissolved completely in organic

solvents.

It produced mainly by F. verticillioides, were isolated from corn that was associated with the

outbreak of leuko-encephalomalacia (LEM) in equine in South Africa in 1970. Fumonisins also caused pulmonary

edema when contaminated corn was fed to pigs.

Fumonisins are also produced by F. proliferatum. Presently, over 28 fumonisins have been isolated and are classified

into four groups (A, B, C, and P). Fumonisin B1 (FB1) is the most commonly found, comprising 70–80% of the total

fumonisins family. FB1 commonly contaminates maize kernels.

Fumonisins can also occur in sorghum, wheat, barley, soybean, asparagus spears, figs, black tea, and medicinal

plants. In the US, F. verticillioides contaminate about 80% of all harvested corn.

In China, FB1, FB2, and FB3 were detected in 98.1% of corn product samples collected from Shandong Province in

2014. (Dauarte et al,2000).

FB1 is the most prevalent fumonisin in human food and also the most toxic, classified in Group 2B (probably

carcinogenic) by IARC. Structurally, fumonisins are similar to sphinganine, and FB1 exerts its toxic effects by

disrupting sphingolipid metabolism.

Fumonisins target mainly the liver and the kidney and cause severe toxicity in experimental animals. Due to their

hydrophilicity, there are no carryovers of fumonisins into milk in cattle, and little FB1 accumulates in edible tissues.

WHO set the provisional maximum tolerable daily intake at 2 µg/kg body weight.

FDA has set the recommended maximum levels at 2–4 ppm for fumonisins in human foods such as corn and

processed corn-based products and at 5–100 ppm in different animal feeds, which it considers achievable with the

use of good agricultural and good manufacturing practices.

In 2007, the EU amended the legislation on the maximum levels of fumonisins in maize and maize-based products

to 4 ppm in unprocessed maize and 1 ppm in maize intended for direct human consumption.

Trichothecenes

Trichothecenes (TCTC) were recognized as causing alimentary toxic leukemia (ATA) toxicosis in the USSR in 1932.

Over 150 TCTC variants have been identified to date, but only a few are of agricultural importance.

TCTC is the most chemically diversified of all mycotoxins. Among TCTC, deoxynivalenol (DON) is the most common

and well-studied but is also among the least toxic.

Also produced mainly by Fusarium species fungi. However, Acremonium (Cephalosporium), Cylindrocarpon,

Dendrodochium, Myrothecium, Trichoderma, Trichothecium, and Stachybotrys species are also able to produce

TCTC.

The Major Groups Of Mycotoxins Causing Human And Animal Illness

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Fusarium species usually infect and produce TCTC in crop plants in the field. Economically, the most

important TCTC producers are F. graminearum and F. culmorum which cause Fusarium Head Blight (FHB), a destructive disease of cereal grain crops with worldwide economic impact.

TCTC mainly contaminates cereals such as wheat, barley, oats, rye, maize, and rice. They may also be present in

soybeans, potatoes, sunflower seeds, peanuts, and bananas, and have been found in some processed foods derived

from cereals (bread, breakfast cereals, noodles, and beer).

DON is the most widely distributed Fusarium mycotoxin, contaminating cereals in Japan, Korea, Europe, Southern

Africa, and Australia.

The IARC has placed DON in carcinogenesis Group 3. The oral LD50 for DON is 46–78 mg/kg. Human exposure to

It also-contaminated grains have been reported to cause nausea, vomiting, diarrhea, abdominal pain, headache,

dizziness, and fever.

Generally, the common symptoms of TCTC toxicity in animals are slow growth, lowered milk

production in cattle, feed refusal, drop in egg production in laying hens, intestinal hemorrhage, and suppression of

immune responses.

TCTC is highly toxic and can easily penetrate cell membrane lipid bilayers to react with DNA,

RNA, and cellular organelles 1.

The major mechanism of TCTC toxicity is inhibition of ribosomal protein synthesis, which is followed by secondary

disruption of DNA and RNA synthesis.

The US FDA has established advisory levels of 1 ppm DON for a finished wheat product such as flour and bran that

may be consumed by humans and 5 ~ 10 ppm for all grains and grain by-products intended for animal consumption.

(Robens,2000).

Patulin

Patulin is a polyketide mycotoxin discovered in 1943. It is produced by certain species of Penicillium, Aspergillus,

and Byssochlamys growing on fruit and vegetables, with P. expansum recognized as the most fungus for its

production.

While it predominantly contaminates apples, apple juice, and apple products, other fruit including pears, peach, and

grapes may also be vulnerable to patulin contamination.

The Major Groups Of Mycotoxins Causing Human And Animal Illness

Patulin was initially studied as a potential antibiotic, but subsequent research demonstrated human toxicities,

including nausea, vomiting, ulceration, and hemorrhage.

In rodents, the oral LD50 of patulin ranges from 29–55 mg/kg body weight. Although IARC has

expressed much concern about the possible carcinogenicity of patulin, it nevertheless placed patulin in

carcinogenicity Group 3.

The US FDA limits patulin to 50 ppb as an action level in food for human consumption. EU committee has set a

maximum level of 50 ppb for fruit juices and concentrated fruit juices, 25 ppb for solid apple

products, and 10 ppb for juices and foods consumed by babies and is not specified by the manufacturer.

(Robens et al;2000).

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