Aflatoxin
& Ochratoxin
Kekacang
Beracun
Tahukah anda tepung, beras,
gandum, barley, oats, pulut, kekacang dan lain lain bijirin yang anda makan
mungkin mengandungi mikotoksin dan mikotoksin adalah berbahaya kepada tubuh
anda? Terdapat lebih 400 jenis mikotoksin yang ujud dalam dunia ini dan berapa
banyak antaranya yan gdipantau oleh agen pemantau?
Mikotoksin boleh menyebabkan
barah hati. Mikotoksin adalah berbahaya kerana sifatnya tiada berperasa (tawar),
tidak mempunyai bau, tidak berwarna, bersifat stabil dan tahan suhu didih (tidak
rosak oleh haba),
Untuk mengelakkan keracunan
mikotoksin, anda perlu menyimpan bijirin seperti tepung, beras, gandum, barley,
oats, pulut, kekacang dan lain lain bijirin dengan cermat:
1.
Cari yang segar sahaja ( baru dituai )
2.
Elakkan simpan bijirin di tempat rendah, gelap
dan lembab.
3.
Elakkan menyimpan lama
4.
Elakkan menyimpan stok dengan banyak
Abstract
Mycotoxins are secondary metabolites of
molds that have adverse effects on humans, animals, and crops that result in
illnesses and economic losses. The worldwide contamination of foods and feeds
with mycotoxins is a significant problem. Aflatoxins, ochratoxins,
trichothecenes, zearalenone, fumonisins, tremorgenic toxins, and ergot
alkaloids are the mycotoxins of greatest agro-economic importance. Some molds
are capable of producing more than one mycotoxin and some mycotoxins are
produced by more than one fungal species. Often more than one mycotoxin is
found on a contaminated substrate. Mycotoxins occur more frequently in areas
with a hot and humid climate, favourable for the growth of molds, they can also
be found in temperate zones. Exposure to mycotoxins is mostly by ingestion, but
also occurs by the dermal and inhalation routes. The diseases caused by
exposure to mycotoxins are known as mycotoxicoses. However, mycotoxicoses often
remain unrecognized by medical professionals, except when large numbers of people
are involved. Factors influencing the presence of mycotoxins in foods or feeds
include environmental conditions related to storage that can be controlled.
Other extrinsic factors such as climate or intrinsic factors such as fungal
strain specificity, strain variation, and instability of toxigenic properties
are more difficult to control. Mycotoxins have various acute and chronic
effects on humans and animals (especially monogastrics) depending on species
and susceptibility of an animal within a species. Ruminants have, however,
generally been more resistant to the adverse effects of mycotoxins. This is
because the rumen microbiota is capable of degrading mycotoxins. The economic
impact of mycotoxins include loss of human and animal life, increased health
care and veterinary care costs, reduced livestock production, disposal of
contaminated foods and feeds, and investment in research and applications to
reduce severity of the mycotoxin problem. Although efforts have continued
internationally to set guidelines to control mycotoxins, practical measures
have not been adequately implemented.
KEYWORDS
·
Mycotoxins;
·
Fungal
secondary metabolites;
·
Aflatoxins;
·
Aflatoxicoses
1. Introduction
It is difficult to define mycotoxin in a few words. All
mycotoxins are low-molecular-weight natural products (i.e., small molecules)
produced as secondary metabolites by filamentous fungi. These metabolites
constitute a toxigenically and chemically heterogeneous assemblage that are
grouped together only because the members can cause disease and death in human
beings and other vertebrates. Not surprisingly, many mycotoxins display
overlapping toxicities to invertebrates, plants, and microorganisms (Bennett, 1987).
The term mycotoxin was coined in 1962 in the aftermath of an unusual veterinary
crisis near London, England, during which approximately 100,000 turkey poults
died. When this mysterious turkey X disease was linked to a peanut (groundnut)
meal contaminated with secondary metabolites from Aspergillus
flavus (aflatoxins),
it sensitized scientists to the possibility that other occult mold metabolites
might be deadly ( Bennett and Klich,
2003). While all mycotoxins are of fungal origin, not
all toxic compounds produced by fungi are called mycotoxins. The target and the
concentration of the metabolite are both important. Fungal products that are
mainly toxic to bacteria (such as penicillin) are usually called antibiotics.
Fungal products that are toxic to plants are called phytotoxins by plant
pathologists. Mycotoxins are made by fungi and are toxic to vertebrates and
other animal groups in low concentrations. Other low-molecular-weight fungal
metabolites such as ethanol that are toxic only in high concentrations are not
considered mycotoxins (Bennett, 1987).
Mycotoxins are a structurally diverse group of mostly small
molecular weight compounds, produced mainly by the secondary metabolism of some
filamentous fungi, or molds, which under suitable temperature and humidity
conditions, and may develop on various foods and feeds, causing serious risks
for human and animal health. Mycotoxins are secondary metabolites that have no
biochemical significance in fungal growth and development; however, they vary
from simple C4 compounds, e.g., moniliformin, to complex substances such as the
phomopsins (Dinis et al., 2007).
Currently, more than 300 mycotoxins are known, scientific attention is focused
mainly on those that have proven to be carcinogenic and/or toxic. Human
exposure to mycotoxins may result from consumption of plant-derived foods that
are contaminated with toxins, the carry-over of mycotoxins and their
metabolites in animal products such as meat and eggs (CAST, 2003)
or exposure to air and dust containing toxins (Jarvis, 2002).
Toxigenic molds are known to produce one or more of these toxic
secondary metabolites. It is well established that not all molds are toxigenic
and not all secondary metabolites from molds are toxic. Examples of mycotoxins
of greatest public health and agro-economic significance include aflatoxins
(AF), ochratoxins (OT), trichothecenes, zearalenone (ZEN), fumonisins (F),
tremorgenic toxins, and ergot alkaloids. These toxins account for millions of
dollars annually in losses worldwide in human health, animal health, and
condemned agricultural products. Factors contributing to the presence or
production of mycotoxins in foods or feeds include storage, environmental, and
ecological conditions. Often times most factors are beyond human control (Hussein and Brasel,
2001). Ochratoxin A (OTA) is a secondary metabolite
produced by several species of Aspergillus and Penicillium. The
toxin, which is a nephrotoxic and nephrocarcinogenic compound, has mainly been
found in cereals as well as in other products like coffee, wine, dried fruits,
beer and grape juice. It occurs in the kidney, liver and blood of farm animals
by transfer from animal feed. Although its genotoxic power has so far not been
definitively established, zearalenone (ZEA), produced by various species of Fusarium,
in particular Fusarium graminearum and Fusarium culmorum,
has an osteogenous action and is significantly toxic to the reproductive system
of animals ( Milicevic et al., 2010).
Human food can be contaminated with mycotoxins at various stages
in the food chain (Bennett and Klich,
2003) and the most important genera of mycotoxigenic
fungi are Aspergillus, Alternaria, Claviceps, Fusarium, Penicillium and Stachybotrys. The principal classes of mycotoxins
include a metabolite of A. flavus and Aspergillus parasiticus,
aflatoxin B1 (AFB1), the most potent hepatocarcinogenic substance
known, which has been recently proven to also be genotoxic. In dairy cattle,
another problem arises from the transformation of AFB1 and
AFB2 into
hydroxylated metabolites, aflatoxin M1 and M2(AFM1 and
AFM2), which are found in milk and milk products
obtained from livestock that have ingested contaminated feed (Boudra et al., 2007).
In 1993, the WHO-International Agency for Research on Cancer ( World Health Organization International Agency
for Research on Cancer (WHO-IARC), 1993a and World Health Organization International Agency
for Research on Cancer (WHO-IARC), 1993b) evaluated the carcinogenic
potential of AF, OT, trichothecenes, ZEN, and F. Naturally occurring AF were
classified as carcinogenic to humans (Group 1) while OT and F were classified
as possible carcinogens (Group 2B). Trichothecenes and ZEN, however, were not
classified as human carcinogens (Group 3). The health hazards of mycotoxins to
humans or animals have been reviewed extensively in recent years ( Yaling et al., 2008 and Averkieva, 2009).
Mycotoxins are not only hard to define, they are also
challenging to classify. Due to their diverse chemical structures and
biosynthetic origins, their myriad biological effects, and their production by
a wide number of different fungal species, classification schemes tend to
reflect the training of the person doing the categorizing. Clinicians often
arrange them by the organ they affect. Thus, mycotoxins can be classified as
hepatotoxins, nephrotoxins, neurotoxins, immunotoxins, and so forth. Cell
biologists put them into generic groups such as teratogens, mutagens,
carcinogens, and allergens. Organic chemists have attempted to classify them by
their chemical structures (e.g., lactones, coumarins); biochemists according to
their biosynthetic origins (polyketides, amino acid-derived, etc.); physicians
by the illnesses they cause (e.g., St. Anthony’s fire, stachybotryotoxicosis),
and mycologists by the fungi that produce them (e.g., Aspergillus toxins, Penicillium toxins). None of these classifications
is entirely satisfactory ( Bennett and Klich,
2003).
2. Occurrence and significance of mycotoxins
in foods and feeds
Mycotoxicoses in humans or animals are characterized as food or
feed related, non-contagious, non-transferable, non-infectious, and
non-traceable to microorganisms other than fungi. Clinical symptoms usually
subside upon removal of contaminated food or feed. A wide range of commodities
can be contaminated with mycotoxins both pre- and post-harvest (CAST, 2003).
Aflatoxins (AFTs) are found in maize and peanuts, as well as in tree nuts and
dried fruits. OTA is found mainly in cereals, but significant levels of
contamination may also occur in wine, coffee, spices and dried fruits. Other
products of concern are beans, roasted coffee and cocoa, malt and beer, bread
and bakery products, wines and grape juices, spices, poultry meat and kidneys,
pig kidneys and pork sausages (Milicevic et al., 2008).
2.1. Aflatoxins
The aflatoxins were isolated and characterized after the death
of more than 100,000 turkey poults (turkey X disease) was traced to the
consumption of a mold-contaminated peanut meal. The major aflatoxins are called
B1, B2, G1, and G2 (based on their fluorescence under UV
light (blue or green) and relative chromatographic mobility during thin-layer
chromatography) M1 and M2 (produced in milk and dairy products) (Fig. 1)
(D’Mello and MacDonald,
1997). Aflatoxin B1 is the most potent natural carcinogen
known and is usually the major aflatoxin produced by toxigenic strains (Squire, 1981).
Aflatoxins are difuranocoumarin derivatives produced by a polyketide pathway by
many strains of A. flavus and A. parasiticus; in
particular, A. flavus is a common contaminant in
agriculture. Aspergillus bombycis, Aspergillus
ochraceoroseus, Aspergillus nomius,
and Aspergillus pseudotamari are also aflatoxin-producing species,
but they are encountered less frequently ( Peterson et al., 2001).
Aflatoxin contamination has
been linked to increased mortality in farm animals and thus significantly
lowers the value of grains as an animal feed and as an export commodity. Milk
products can also serve as an indirect source of aflatoxin. When cows consume
aflatoxin-contaminated feeds, they metabolically biotransform aflatoxin B1 into a
hydroxylated form called aflatoxin M1 (Van Egmond, 1989).
Aflatoxin is associated with both toxicity and carcinogenicity in human and
animal populations. The diseases caused by aflatoxin consumption are loosely
called aflatoxicoses. Acute aflatoxicosis results in death; chronic
aflatoxicosis results in cancer, immune suppression, and other “slow”
pathological conditions. The liver is the primary target organ, with liver
damage occurring when poultry, fish, rodents, and nonhuman primates are fed
aflatoxin B1. There are substantial differences in species
susceptibility. Moreover, within a given species, the magnitude of the response
is influenced by age, sex, weight, diet, exposure to infectious agents, and the
presence of other mycotoxins and pharmacologically active substances. Thousands
of studies on aflatoxin toxicity have been conducted, mostly concerning
laboratory models or agriculturally important species (Cullen and Newberne,
1994).
Finally, it should be mentioned that Aspergillus oryzae and Aspergillus sojae,
species that are widely used in Asian food fermentations such as soy sauce,
miso, and sake, are closely related to the aflatoxigenic species A. flavus and A. parasiticus.
Although these food fungi have never been shown to produce aflatoxin, they
contain homologues of several aflatoxin biosynthesis pathway genes. Deletions
and other genetic defects have led to silencing of the aflatoxin pathway in
both A.
oryzae and A. sojae ( Takahashi et al., 2002).
2.2. Ochratoxins
Ochratoxin A (OTA) (Fig. 2)
is produced by fungi of the genera Aspergillus and Penicillium. The
major species implicated in OTA production includes Aspergillus ochraceus, Aspergillus carbonarius, Aspergillus melleus, Aspergillus sclerotiorum, Aspergillus sulphureus, Pichia verrucossum.
However, Aspergillus
niger and Pichia purpurescens are less important OTA producers ( Benford et al., 2001). OTA
is a frequent natural contaminant of many foodstuffs such as cocoa beans,
coffee beans, cassava flour, cereals, fish, peanuts, dried fruits, wine,
poultry eggs and milk (Weidenborner, 2001).
The mycotoxin was reported in 35% in “under-five clinics” of breast milks in
Southern province of Sierra Leone with up to 22% cooccurrence with aflatoxins.
However, the scientists observed that whenever OTA was detected in high levels,
AFB1was absent or present at very low levels and vice
versa which suggests some sort of competition between these toxins either at
the production level in foodstuffs or in their rate of absorption in the
gastrointestinal tract. OTA has also been reported as a contaminant of tiger
nuts and fermented maize dough in West Africa (Kpodo, 1996).
2.3. Fumonisins
Fumonisins (B1 and B2) (Fig. 3) are cancer-promoting
metabolites of Fusarium proliferatum and Fusarium verticillioides that have a long-chain hydrocarbon
unit (similar to that of sphingosine and sphinganine) which plays a role in
their toxicity. Fumonisin B1(FB1) is the most toxic and has been shown to promote
tumor in rats and cause equine leukoencephalomalacia and porcine pulmonary
edema. The naturally co-occurring aminopentol isomers (formed by base
hydrolysis of the ester-linked tricarballylic acid of FB1) have been suggested to exert toxic effects due to
their structural analogy to sphingoid bases (Humpf et al., 1998). Consumption
of fumonisin (Fig. 3) has been associated with
elevated human oesophageal cancer incidence in various parts of Africa, Central
America, and Asia and among the black population in Charleston, South Carolina,
USA. Because fumonisin B1 reduces uptake of folate in different
cell lines, fumonisin consumption has been implicated in neural tube defects in
human babies. Some correlation studies have suggested a link between the
consumption of maize with high incidence of F. verticillioides and fumonisins and the high incidence
of human oesophageal carcinoma in certain parts of South Africa ( Marasas et al., 2004).
2.4. Trichothecenes
The trichothecene mycotoxins (TCT) (Fig. 4)
comprise a vast group of over 100 fungal metabolites with the same basic
structure. Several fungal genera are capable of producing TCT; however, most of
them have been isolated from Fusarium spp. All trichothecene contain an
epoxide at the C12,13 positions, which is responsible for
their toxicological activity. At the cellular level, the main toxic effect of
TCT mycotoxins appears to be a primary inhibition of protein synthesis. TCT
affect actively dividing cells such as those lining the gastrointestinal tract,
the skin, lymphoid and erythroid cells. The toxic action of TCT results in
extensive necrosis of the oral mucosa and skin in contact with the toxin, acute
effect on the digestive tract and decreased bone marrow and immune function (Schwarzer, 2009).
The trichothecene mycotoxins occur worldwide in grains and other commodities.
Toxin production is greatest with high humidity and temperatures of
6–24 °C. Natural occurrence of TCT has been reported in Asia, Africa,
South America, Europe, and North America (Scott, 1989).
Trichothecenes have been detected in corn, wheat, barley, oats, rice, rye,
vegetables, and other crops. They are common contaminants of poultry feeds and
feedstuffs and their adverse effects on poultry health and productivity have
been studied extensively (Leeson et al., 1995).
Examples of type A TCT include T-2 toxin (T-2) and HT-2 toxin (HT-2), and
diacetoxyscirpenol (DAS). Fusarenone-X (FUX), deoxynivalenol (DON), and
nivalenol (NIV) are some of the common naturally occurring type B TCT. Types A
and B trichothecene are distinguished by the presence or absence of a carbonyl
group at the C8 position, respectively (Schwarzer, 2009).
Nivalenol was usually found
associated with DON and its derivatives (mono-acetyldeoxynivalenols), along
with FUX, which were produced by F.
graminearum, Fusarium
cerealis, Fusarium
culmorum in the
southern areas and in northern areas, by Fusarium poae.
Moreover, from central to northern European countries, moniliform has been
consistently reported, as a consequence of the widespread distribution of Fusarium avenaceum,
whereas the occurrence of T-2 derivatives, such as T-2 and HT-2, and DAS have
been recorded in conjunction with sporadic epidemics of Fusarium sporotrichioides and F. poae ( Bottalico and Perrone, 2002).
Rainbow trout and channel catfish trial data indicates the
impact of T-2 toxin (up to 5 ppm) or Don (up to 15 ppm) diet
supplementation on growth rate, feed efficiency, hematocrit, intestinal
hemorrhaging (Manning et al., 2003).
2.5. Zearalenone
Zearalenone (Fig. 5) is a mycotoxin produced
by F.
graminearum and
other Fusarium molds using corn, wheat, barley, oats and
sorghum as substrates. It is a non-steroidal compound that exhibits
oestrogen-like activity in certain farm animals such as cattle, sheep and pigs.
Zearalenone is a phenolic resorcyclic acid lactone with potent oestrogenic
properties, produced primarily by Fusarium ( Schwarzer, 2009). Zearalenone is a
phytoestrogenic compound known as 6-(10-hydroxy-6-oxo-trans-1-undecenyl)-β-resorcylic
acid μ-lactone. It is a metabolite primarily associated with several Fusarium species (i.e. F. culmorum, F. graminearum, and F. sporotrichioides) with F. graminearum being the species most responsible for the
oestrogenic effects commonly found in farm animals. Alcohol metabolites of ZEN
(i.e. α-zearalenol and β-zearalenol) are also oestrogenic ( Cheeke, 1998a).
2.6. Moniliformin
Moniliformin (i.e. a potassium or sodium salt of
1-hydroxycyclobut-1-ene-3,4-dione, Fig. 6) is produced by several Fusarium species (mainly F. proliferatum)
and is usually found on the corn kernel. It can be transferred to next
generation crops and survive for years in the soil. Although both FB1 and
moniliformin are produced by the same fungal species (F. proliferatum)
no structural resemblance is found between the two toxins ( Price et al., 1993).
3. Negative effects of mycotoxins on humans
Mycotoxicoses, like all toxicological syndromes, can be
categorized as acute or chronic. Acute toxicity generally has a rapid onset and
an obvious toxic response, while chronic toxicity is characterized by low-dose
exposure over a long time period, resulting in cancers and other generally
irreversible effects (James, 2005).
Prior to the discovery and implementation of modern milling practices, Fusarium species have been implicated in
several human outbreaks of mycotoxicoses. Cereal grains contaminated with F. sporitrichoides and F. poae were implicated in alimentary toxic
aleukia in Russia from 1932 to 1947. Symptoms included mucous membrane
hyperaemia, oesophageal pain, laryngitis, asphyxiation, gastroenteritis, and
vertigo ( Lewis et al., 2005).
Aflatoxicosis is a toxic hepatitis leading to jaundice and, in
severe cases, death. Repetitive incidents of this nature have occurred in Kenya
(during 1981, 2001, 2004 and 2005), India, and Malaysia (Shephard, 2004 and Lewis et al., 2005). AFB1 has
been extensively linked to human primary liver cancer in which it acts synergistically
with HBV infection and was classified by the International Agency for Research
on Cancer (IARC) as a human carcinogen (Group 1 carcinogen) (IARC, 1993).
This combination represents a heavy cancer burden in developing countries. A
recent comparison of the estimated population risk between Kenya and France
highlighted the greater burden that can be placed on developing countries (Shephard, 2006).
The largest risk of AF to humans is usually the result of
chronic dietary exposure. Such dietary AF exposures have been associated with
human hepatocellular carcinomas, which may be compounded by hepatitis B virus.
Approximately 250,000 deaths are caused by hepatocellular carcinomas in China
and Sub-Saharan Africa annually and are attributed to risk factors such as high
daily intake (1.4 μg) of AF and high incidence of hepatitis B (Wild et al., 1992).
Aflatoxins have been found in tissues of children suffering from Kwashiorkor
and Reye’s syndrome and were thought to be a contributing factor to these
diseases. Reye’s syndrome, which is characterized by encephalopathy and
visceral deterioration, results in liver and kidney enlargement and cerebral
edema (Blunden et al., 1991).
Aflatoxin has long been linked to Kwashiorkor, a disease usually considered a
form of protein energy malnutrition, although some characteristics of the
disease are known to be among the pathological effects caused by aflatoxins in
animals. Aflatoxin exposure was associated with reduced levels of secretory
immunoglobulin A (IgA) in Gambian children (Turner et al., 2003).
Changes in differential subset distributions and functional alterations of
specific lymphocyte subsets have been correlated with aflatoxin exposure in
Ghanaian adults and indicate that aflatoxins could cause impairment of human
cellular immunity that could decrease resistance to infections (Jiang et al., 2005).
Of the other health risk factors, the morbidity and mortality
associated with unsafe sex, unsafe water and indoor smoke, arises from
infectious diseases, such as HIV/AIDS, infectious diarrhoea and lower
respiratory tract infection, respectively. The immunological suppression
associated with aflatoxin and possibly DON could adversely affect all these
outcomes. The modulating effect of aflatoxins in cases of zinc, iron and
vitamin A deficiency in human health is less clear, but evidence from animal
nutrition would suggest it could be significant (Williams et al., 2004).
Fumonisins have been implicated in one incident of acute food-borne disease in
India in which the occurrence of borborygmy, abdominal pain, and diarrhoea was
associated with the consumption of maize and sorghum contaminated with high
levels of fumonisins. Fumonisin B1, the most
abundant of the numerous fumonisin analogues, was classified by the IARC as a
Group 2B carcinogen (possibly carcinogenic in humans) (IARC, 2002).
Fumonisins, which inhibit the uptake of folic acid via the folate receptor,
have also been implicated in the high incidence of neural tube defects in rural
populations known to consume contaminated maize, such as the former Transkei
region of South Africa and areas of Northern China (Marasas et al., 2004).
Both DON and ZEN from toxic Fusaria have been linked to scabby grain
toxicoses in the USA, China, Japan, and Australia. Symptoms included nausea,
vomiting, and diarrhea. Fumonisin B1 was associated with an illness
outbreak in India with symptoms of acute onset of abdominal pain and diarrhea.
Fumonisins also have been implicated in oesophageal cancer in China (Yoshizawa et al., 1994).
However, with limited causal relationships and the presence of several
confounding factors, data compiled by the International Agency for Research on
Cancer were not conclusive for F carcinogenicity in humans (Casegnaro and Wild,
1995). Trichothecenes have been suggested as potential
biological warfare agents. For example, T-2 toxin was implicated as the
chemical agent of ‘yellow rain’ used against the Lao Peoples Democratic
Republic from 1975 through 1981 (Peraica et al., 1999).
In an investigation of similar biological warfare agents in Cambodia from 1978
to 1981, T-2 toxin, DON, ZEN, nivalenol, and DAS were isolated from water and
leaf samples collected from the affected areas (Peraica et al., 1999).
Clinical symptoms preceding death included vomiting, diarrhea,
hemorrhage, breathing difficulty, chest pain, blisters, headache, fatigue, and
dizziness. In addition to nephritic congestion, autopsy findings included
necrosis of the lining of the stomach and upper small intestine, lungs, and
liver. It should be noted, however, that the origin of the samples of yellow
rain is still a subject of debate. For example, one theory attributed the
source of illnesses to unidentified endemic factors because the yellow rain was
found to be a native bee fecal material devoid of mycotoxins (Seeley et al., 1985).
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