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Abstract
Some filamentous fungi are able to grow in food and produce toxic metabolites.
It occurs mainly in grains, cereals, oilseeds and some by-products. The growth of
fungi in a particular food is governed largely by a series of physical and chemical
parameters. The production of toxic metabolites is not confined to a single group
of molds irrespective of whether they are grouped according to structure, ecology,
or phylogenetic relationships. Mycotoxins can be carcinogenic and cause several
harmful effects to both human and animal organisms, in addition to generating
large economic losses. The major mycotoxins found in food are the aflatoxins,
fumonisins, ochratoxins, patulin, zearalenone, and trichothecenes, generally stable
at high temperatures and long storage periods. Considering the difficult prevention
and control, international organizations for food safety establish safe levels of these
toxins in food destined for both human and animal consumption. Good agricultural
practices and control of temperature and moisture during storage are factors which
contribute significantly to inhibit the production of mycotoxins. The use of some
fungistatic products, such as essential oils and antioxidants, as well as physical,
mechanical, chemical, or thermal processing, represents important methods to have
the concentration of mycotoxins reduced in food.
1
Cell Growth
1. Introduction
2. Fungi
Fungi are able to grow in practically all ecological niches; however, they can
be found prevailing particularly in dead organic matters present in the soil. They
include eukaryotic organisms commonly known as yeasts, which normally grow in
the form of single cells, and molds, which grow by forming ramified chains called
hyphae. Even though most fungi are harmless to human beings, the exposition to
specific lineages and their metabolites may result in some clinical manifestations in
men and other animals.
a. Infections or diseases derived from the invasion of living tissue. The growth
of a fungus on the top of or inside a body is named mycosis. Mycoses can have
varied severity, encompassing from relatively benign and superficial infections
to severe diseases that threaten life.
The major toxigenic strains of interest for the public health belong to the genera
Aspergillus spp., Penicillium spp., and Fusarium spp. It is important to highlight that
not all fungi produce mycotoxins as well as that a single fungus species can produce
many secondary toxic compounds. The presence of a mycotoxin in food is necessar-
ily conditioned to fungus development, but it does not mean that a product without
any fungi could not contain mycotoxins [2]. A cereal stored under poor conditions
of temperature and moisture provides a favorable medium for fungus development
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and the production of mycotoxins. Once a mycotoxin is produced, even upon the
destruction of the fungus biomass, through a drying process, for example, the
metabolites excreted remain in the product.
As heterotrophs, fungi require organic compounds for both synthesis of biomass
(anabolic metabolism) and production of energy to drive these reactions (catabolic
metabolism). These aspects are referred to as primary metabolism. The secondary
metabolisms are distinct from primary metabolism in so far as they occur optimally
after a phase of a balanced growth and are often, but not always, associated with
morphogenetic changes such as sporulation; the production of particular secondary
metabolites is usually restricted to a small number of species and may be species,
or even strain, specific; it has not generally been possible to rationalize the bio-
logical function of secondary metabolites, although some are very active against
microorganisms (antibiotics), plants (phytotoxins), or animals (mycotoxins).
Although secondary metabolites in general, and mycotoxins specifically, do not
form a neat and a recognizable group of organic structures, they can be classified in
terms of the biosynthetic pathways leading to their production. This is so because
the processes of primary and secondary metabolism are linked by a relatively small
number of simple intermediates such as acetyl coenzyme A, mevalonic acid, and
amino acids [3–5].
3
Cell Growth
4. Mycotoxins
Mycotoxins have been known for a very long time, but they only became more
intensively studied after an incident occurred in 1960 in England, involving the
death of 100,000 birds fed on feed contaminated with fungus Aspergillus flavus.
Mycotoxins are produced mainly by mycelial structures present in filamentous
fungi. Even though their function for produced lineages is yet to be clarified,
mycotoxins are secondary metabolites that apparently do not present a biochemical
meaning to fungus growth and development [7, 15].
According to the Food and Agriculture Organization (FAO), it is estimated that
the contamination of food products by fungi and their toxic metabolites generates
qualitative and quantitative losses for around 25% of the agricultural food produc-
tion worldwide, occurring majorly in regions of tropical and subtropical climate,
where higher temperature and moisture favor microbial proliferation [16, 17].
Primary metabolites of fungi, such as of other organisms, are essential to
growth, while secondary ones are formed during the final exponential growth phase
and have not a clear significance to the growth or metabolism of the organism [1–3].
In general, these metabolites appear to be formed whenever large amounts of
primary metabolites precursors, such as amino acids, acetate, and pyruvate, among
others, are accumulated. The synthesis of mycotoxins represents a way for fungi to
reduce the amount of precursors, which are not required to metabolism [1–3].
They are constituted by a large variety of chemical assembles, which provides
them with several biological activities, classified according to the toxicity level
exerted on human and animal organisms [2] possibly with carcinogenic, mutagenic,
teratogenic, cytotoxic, neurotoxic, nephrotoxic, immunosuppressant, and estro-
gen effects. However, its toxicity largely depends on the amount ingested, time of
exposition, and possible synergy with the ingestion of many different mycotoxins
simultaneously, in addition to individual physiological conditions [4].
Mycotoxin ingestion can produce both acute and chronic toxicities. Acute is
characterized by a rapid onset and an obvious toxic response including rapid death.
Chronic is resulting from low-dose exposure to mycotoxins over a long period of time,
with toxic responses including cancers such as hepatocellular carcinoma [18, 19].
The International Agency for Research on Cancer (IARC) in Lyon (France)—
through its IARC Monographs program—has performed the carcinogenic hazard
assessment of some mycotoxins in humans, on the basis of epidemiological data,
studies of cancer in experimental animals, and mechanistic studies. There are five
groups classified according to the scientific evidence for their carcinogenicity:
Group 1, carcinogenic to humans; Group 2A, probably carcinogenic to humans;
Group 2B, possibly carcinogenic to humans; Group 3, not classifiable as to its
carcinogenicity to humans; and Group 4, probably not carcinogenic to humans.
Carcinogenic effects and related mechanisms of some mycotoxins (e.g., aflatoxins)
are well-known. However, for some other important mycotoxins (e.g., OTA, FUM
B1, and FUM B2), there is a need for continued research on understanding these
mechanisms [20–24].
4.1 Aflatoxins
Many types of aflatoxin (14 or more) occur in nature, but only four of them are
particularly dangerous to humans and animals. Aflatoxins are mainly produced by
species of Aspergillus flavus and Aspergillus parasiticus and classified in aflatoxins
B1 and B2 and G1 and G2. Their name derives from the fluorescence emitted after
absorption of ultraviolet light at 365 nm (B, blue; and G, green). They are char-
acteristically heat-resistant and bear the process of sterilization with a structure
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remaining unaltered for long periods of storage. Their chemical structure allows
good solubility in organic solvents and are insoluble in water proving sensitive in
alkaline medium, which decreased their toxicity [22]. The group of aflatoxins is
considered by the IARC as belonging to Group 1—cancer-causing substances to
men [21].
Mycotoxin B1 is pointed out as the most toxic in the group and can generate
metabolites in the organism of mammals (M1). Aflatoxin M1, generated by B1
metabolism, is transported to milk at a proportion of 1% of the total ingested and
can also be found in animal tissues in which there is a high exposition to this toxin.
Subsequently, humans can ingest this aflatoxin through breast milk, milk, and
milk-derived products, especially in areas where grains and cereals of poor quality
are used to feed animals [17–23].
Birds are the most sensitive animals to aflatoxins, and whenever ingested in
contaminated feed, they present fast absorption through the gastrointestinal tract.
The effects include damages to the liver, harm to the productivity and reproductive
efficiency, decreased production of eggs, lower quality of egg shell, lower quality
of carcass, and increased susceptibility to diseases. Pigs are, somehow, less sensitive
than birds. Aflatoxin is also hepatotoxic to these animals, and its chronic effects are
largely attributed to damage to the liver. In cattle, the primary symptom is reduction
in weight gain. In addition, milk production is reduced [25–27].
Aflatoxins occur mainly in products such as peanut and nuts, maize, and cotton-
seed, among others, which is associated with pre-crop contamination. Cultures such
as coffee, rice, and spices can also be contaminated by these toxins post-crop [26].
Many countries introduced legislation specific to mycotoxins. Most of these
legislation rules are regarding aflatoxins, alkaloids of ergot, deoxynivalenol, and
ochratoxins. Even though legal measures are yet to be uniformed at a worldwide
level, the Codex Alimentarius Commission is gathering efforts to establish interna-
tional guidelines regarding levels of mycotoxins. For aflatoxins, the Food and Drug
Administration established the maximum limit of 20 ppb to maize, peanut, cotton
bran, and other food and ingredients for animals [27–31].
4.2 Ochratoxin A
5
Cell Growth
4.3 Patulin
4.4 Trichothecenes
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provides toxicity. These toxins are classified in type A, in which toxins T-2, HT-2,
15-monoacetoxyscirpenol (15-MAS), and diacetoxyscirpenol (DAS) are found, and
type B, in which deoxynivalenol (DON) occurs. Deoxynivalenol is an epoxy-
sesquiterpenoid which occurs naturally combined with 3-acetyl-deoxynivalenol
(3AcDON) and 15-acetyl-deoxynivalenol (15AcDON), which increases DON toxicity.
According to the IARC, DON is classified in level 3, that is, it does not represent a risk
of cancer induction, although co-occurrence with aflatoxin may increase aflatoxin
carcinogenicity. DON can also coexist combined with zearalenone [1, 2, 37].
Despite the existence of a relatively large amount of different trichothecenes,
their natural occurrence in food and feed is mainly related to nivalenol, deoxyniva-
lenol, toxin T-2, diacetoxyscirpenol, and less often furarenone-X, toxin HT-2, and
neosolaniol.
DON is probably the most largely distributed mycotoxin in food and feed often
detected in wheat, barley, rye, malt, oat, maize, and consequently products derived
from these cereals, such as flours and beers, and less often rice, sorghum, and
triticale. It is a heat-resistant toxin which is not altered during food processing, in
addition to being stable over long storage periods [37, 38].
Discovered in the early 1970s, DON is also popularly known as vomitoxin for its
acute effect on the ingestion of high doses causing symptoms similar to enterotoxins
of Staphylococcus aureus and Bacillus cereus, such as nausea, vomit, abdominal pains,
diarrhea, leukopenia, bleeding, and even death in humans and animals [37, 38].
Pig is the most sensitive animal to DON, and the chronic effects of ingestion of
contaminated feed result in reduced weight gain and growth, infertility, including
the birth of animals with malformation, and miscarriage. Birds are more tolerant
than pig, and the effects of intoxication are lower quality and weight of the eggs
produced. Cattle are more tolerant, possibly due to the toxin degradation in second-
ary metabolites in the rumen. The effects in cattle include lower feed consumption
and conception rate in addition to reduced milk production [2, 37].
The Codex Alimentarius Commission (CAC) establishes the maximum level of
2 μg/kg for DON for wheat, maize, and barley. The European Union, in turn, proposes
0.75 μg/kg for cereals and flour and 0.2 μg/kg for wheat germ [38].
4.5 Zearalenone
7
Cell Growth
conditions (high moisture). The detection of this mycotoxin in bird feed has been
considered a biomarker for other toxins belonging to the genus Fusarium [31].
Despite some evidence, the IARC assessed the carcinogenicity of zearalenone
and found it to be a possible cancer-causing substance to humans. Zearalenone
residues do not seem to be an issue after consumed.
4.6 Fumonisins
They were discovered in 1988 and described as fumonisins B1, B2, and B3, in
which B1 occurs more frequently. However, fumonisins constitute a group encom-
passing over 16 substances already identified, called B1 (FB1, FB2, FB3, and FB4),
A1, A2, A3, AK1, C1, C3, C4, P1, P2, P3, PH1a, and PH1b. They are highly water-
soluble unlike other mycotoxins and do not have an aromatic structure or a single
chromophore to analytically facilitate its identification, therefore being difficult to
identify through ultraviolet spectrum [25].
These substances are produced by several species of the genus Fusarium,
especially by Fusarium verticillioides (previously classified as F. moniliforme), F.
proliferatum, and F. nygamai, in addition to Alternaria alternata. Other species, such
as F. anthophilum, F. dlamini, F. napiforme, F. subglutinans, F. polyphialidicum, and F.
oxysporum, also have been included in the group of these mycotoxin products [25, 38].
Fumonisins have been found as a common contaminant in maize-based food
and feed. When ingested, fumonisins present low bioavailability and are rapidly
metabolized and excreted. The carcinogenic nature of fumonisins does not seem to
involve an interaction with DNA. Their mode of action is related to their toxicity
in the interference of the biosynthesis of sphingolipid, which are very important to
maintain the integrity of the cell membrane, regulation of receptors of cell surface,
ion pump, regulation of growth factors, and other vital systems for the functioning
and survival of the cell. In addition, fumonisins are potent immunosuppressant
agents and can enhance the susceptibility to diseases [38–44].
These toxins cause many diseases in animals, such as leukoencephalomalacia
(LEME) in horses and pulmonary edema in pigs. LEME is a noninfectious, highly
fatal disease which affects the central nervous system of horses and other equines
with a large distribution worldwide and considered a disease derived from regions
of temperate, tropical climate. LEME involves metabolic alterations that produce
the softening of the white substance of the encephalon as well as its liquefaction,
which occurs due to a mycotoxin present in the feed. The disease occurs because of
the need to supplement horse diet with grains of maize or feed containing them in
their formulation due to the lack of fodder in pastures [43].
Even though their effects on human beings are difficult to determine, fumoni-
sins have been statistically associated with high occurrence of esophageal cancer
in South Africa and liver cancer in certain endemic areas in China. Based on toxi-
cological evidence, the IARC declared the toxins of F. moniliforme as potentially
carcinogenic to humans (Class 2B) [44].
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Recently, with the modernization of the means to detect the toxins, such as high-
performance liquid chromatography associated with mass spectrometry, many other
compounds derived from mycotoxins were discovered, and the term “mask myco-
toxin” made way to the name of modified mycotoxins. This denomination classifies
all substance derived from free mycotoxin, that is, all toxic substance originated by
the secondary metabolism of fungi, which through a biological process (human, ani-
mal metabolism or even through the defense mechanism of plants) or technological
process (food processing), have their structure altered as well as polarity, solubility,
and molecular mass, originating a new substance with characteristic toxicity or able
to reinforce the damages caused by parental mycotoxin [45, 46].
Some examples of modified mycotoxins are N-(1-deoxy-D-fructos-1-yl)-
fumonisin B1 (NDF-FB1) and N-(carboxymethyl)-fumonisin B1 (NCM-FB1)
formed in a Maillard reaction between fumonisins and reducing sugars and reaction
of reduction occurring in DON when animal feed is treated with sodium bisulfite
generating sulfonated DON [46].
Cereals, grains, and oilseed are often infected by insects and toxigenic fungi
when still in the field interfering directly in the quality and productivity of food.
Controlling fungi infestations is not an easy task for involving climatic and environ-
mental issues which frequently cannot be controlled by men. Therefore, it is crucial
to disseminate and implement techniques for good agricultural practices, indis-
pensable to minimize problems related to the production of mycotoxins and quality
of the food in the field. Some of these techniques involve choosing the variety to be
cultivated by preferring lineages that are more resistant to attacks of plagues and
microorganisms, good soil preparation, and turnover of cultures. It is also impor-
tant to rationally employ agricultural pesticides by replacing them with sustainable
techniques for plague control whenever possible, such as biological products, oils,
and natural extracts, seeking to protect the cultivation and the environment [47].
The crop at the correct maturation point and the regulation of agricultural
implements to soften mechanical damages to beans and grains are factors which
combined with good storage practice can reduce fungus infestations in food
products. The main storage practices encompass the improvement of the products
received by removing impurities derived from the field, the control of moisture
through drying process at recommended levels, good ventilation, cleansing of the
storage location, and control of insects and rodents, in addition to a system to rela-
tive air humidity.
In addition to good agricultural and storage practices, some strategies for the
detoxification of food and feed contaminated with mycotoxins have emerged as an
effort to reduce or eliminate their toxic effects through chemical, physical, and bio-
logical methods. Some of them involve the application of gamma irradiation, ozone
(O3), and some microbial strains and fungus parasites able to inhibit the production
or decrease the toxicity of some secondary metabolites like Streptomyces rimosusand
and Gliocladium roseum, respectively. These methods are essential to improve food
safety, prevent economic losses, and retrieve contaminated products [48, 49].
6. Conclusion
9
Cell Growth
environment in which it is growing. Even if a strain of mold has the genetic poten-
tial to produce a particular mycotoxin, the level of production will be influenced
by the nutrients available. Even when the nutritional requirements are suitable
for mycotoxin biosynthesis, physical parameters, such as temperature and water
activity, will influence production. In nature there are many other factors inter-
acting with the growth and metabolism of a mold. There may be, for example,
antimicrobial agents produced by other microorganisms, by the plant on which
the mold is growing, or added as biocides during crop husbandry. Mycotoxins have
attracted worldwide attention not only because of their perceived impact on human
health but also because of the economic losses accruing from contaminated foods.
Mycotoxins have been extensively studied as well as their impact on human health.
It is clear that food contaminated with toxic substances are not proper for either
human or animal consumption. Considering that mycotoxins are natural contami-
nants and practically impossible to be completely eliminated from food, interna-
tional food safety organizations provide guidance on the serious risks of mycotoxins
to human health by updating and establishing safe levels of ingestion for these
toxins. As a short-term solution, methods of prevention and food detoxification
have been offered to producers aiming at providing means to enlarge the availability
of safe food to the population worldwide.
Author details
© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms
of the Creative Commons Attribution License (http://creativecommons.org/licenses/
by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.
10
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DOI: http://dx.doi.org/10.5772/intechopen.86533
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