Fumonisins - Do we know the risks?

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Fumonisins DO WE KNOW THE RISKS?

Nemanja Todorović, Marko Vasiljević, Jog Raj, Hunor Farkaš, and Zdenka Jakovčević PATENT CO,. Mišićevo, Serbia

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Fumonisins are a significant health risk to livestock, and potentially also to humans There are 6 types of Fumonisins: B1, B2, B3, B4, A1 and A2

Fumonisins are naturally occurring toxins produced by several species of Fusarium fungi (molds), with

Fusarium moniliforme recognized as the largest producer of this mycotoxin. Other species such as F. proliferatum, F. nygamai, F. anthophilum, F. dlamini and F. napiforme are also producers.

Only Fumonisin B1 (FB1), B2 (FB2) and B3 (FB3) are toxicologically significant whereas the most predominant FB1 corresponds to 70% of fumonisins. In comparison to other mycotoxins, fumonisins are highly soluble and have greater capacity to spread easily and contaminate high volume of water and feedstus. FB1 is classified as a potential human carcinogen (class 2B) by International

Agency for Research on Cancer (IARC) and has been linked to acute toxicity in farm animals (horses and swine), including hepatotoxicity and nephrotoxicity.

70% -FB1

30% - Other

Raw materials affected Fungi of the Fusarium genus are FB1 and FB2 can be found as a natural contaminant

often called, field fungi. Insect

in cereals, specially corn and wheat, usually in

damage, adverse weather with

concentrations that generally induce subclinical

temperatures between 15 and 25°C and

intoxications in different species.

high contents of substrate humidity i.e. above 20% or water activity higher than 0.88 favor fumonisins production.

High humidity + Mild temperatures = Production of fumonisins

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Fusariosis Fungi of Fusarium genus are widespread worldwide and are the cause of economically significant diseases of cultivated and other plants called FUSARIOSIS. It can be found in grains e.g corn, wheat etc. In wheat, this disease can cause yield reductions of up to 70%.

Corn mycotoxins survey 2018 Fumonisins are found globally in grains and other feed materials. Recent mycotoxins survey conducted by PATENT CO shows that corn harvested around the world in 2018 and 2019 is mostly contaminated with fumonisins. In 2018 fumonisins were present in most of the samples (78%) with a median of 668 ppb and a total of 95% corn samples were contaminated with one or more mycotoxins.

yield reductions up to

70%

78%

samples contained Fumonisins

95%

corn samples were contaminated with one or more mycotoxins

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1.

ASIA

100 90

94

80 70 60

94

72

50 40 30 20 10 0

26 11

10 DON

AFB1

FB1

FB2

T-2

OTA

ZON

Fig 1: Percentage of mycotoxins detected in Asia.

2.

EUROPE 80 70

67

60 50

53

40 30

33 25

20 10

4

0 DON

AFB1

FB1

FB2

T-2

20

OTA

25

ZON

Fig 2: Percentage of mycotoxins detected in Europe.

3.

NORTH & SOUTH AMERICA

100 90

99

80 70 60

80

50 40 30 20 10

22

8

DON

AFB1

0

FB1

FB2

6

3

21

T-2

OTA

ZON

Fig 3: Percentage of mycotoxins detected in America.

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Corn mycotoxins survey 2019 Analysis of mycotoxins from corn samples in 2019 showed that 92% of the samples were contaminated

92%

with one or more mycotoxins.

samples contaminated with 1 or more mycotoxins

Fumonisins were detected in 82 % of samples, DON in 27%, AFB1 in 9%, T-2/HT-2 in 12% and ZON in 17 % of samples from the various countries.

These results demonstrate that fumonisins, type B trichothecenes and zearalenone were the predominant mycotoxins in the corn samples obtained from 2019 harvest in the different regions of the world.

FUMONISINS

82%

DON

27%

T-2/HT-2

12%

ZON

17%

AFB1

9%

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Pathogenesis The toxic effects of fumonisins are essentially the result of inhibiting sphingolipids synthesis (lipoprotein such as sphinganine and sphingosine), which controls cellular communication. The fumonisins are structurally similar to sphingosine, which forms a primary part of sphingolipids, a class of cell membrane lipids that include sphingomyelin, an important phospholipid. Fumonisins inhibit the sphinganine (sphingosine) N-acyltransferase (ceramide synthase), a key enzyme in lipid metabolism, resulting in disruption of this pathway.

This enzyme inhibition by fumonisins produces a disruption of sphingolipid metabolism resulting in increased sphinganine and sphingosine along with a decrease in complex sphingolipids in the serum and tissues of animals, which is commonly accepted as the mechanism of action for FUMONISIN toxicity in most species

(Smith et al., 2018).

Alteration of sphinganine-to-sphing osine ratio (Sa/So ratio) is used as a sensitive biomarker of fumonisins exposure.

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Fumonisins’ toxicity to animals EQUINE

The clinical signs associated

HIGH

with fumonisins’ toxicity vary significantly between species. This effect is dependent on primary target organ as safe levels of Fumonisins in feed are different

POULTRY

MEDIUM

SWINE

HIGH

for all animal species.

RUMINANTS AQUACULTURE

LOW MEDIUM

FUMONISINS ARE SEVERE IMMUNOSUPPRESSANTS AT VERY LOW CONCENTRATIONS

Typical mycotoxin induced symptoms are usually correlated with acute intoxications. However, another important fact is that Fumonisins impair immune response in many ways. Following oral intake of low amounts of these mycotoxins, firstly, the gastro-intestinal epithelial cell layer is exposed to these toxins. Fumonisins alter the different intestinal defense mechanisms including epithelial integrity, cell proliferation, and cytokine production. Since the intestinal tract is a major entrance to many enteric pathogens and their toxins, mycotoxin exposure can result in a greater susceptibility to enteric infections in animals consuming feed contaminated with these toxins. intestinal permeability by DON, T-2, FB1

cell proliferation by DON, T-2, FB1

altered cytokines production by DON, T-2, nivalenol, FB1, ZEN

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Horses – extremely sensitive Fumonisins can be extremely harmful to horses. When present in corn or other grains, fumonisins can result in moldy corn poisoning or leukoencephalmalcia. The disease syndrome was named

Leukoencephalomalacia due to the type (malacia = softening [due to necrosis]) and distribution (leuko = white matter) of the most prominent lesion in the brain. Equine are the only species in which fumonisins induce this lesion. Feed manufacturers selling corn or horse feed containing corn should Common symptoms are, horses become disoriented, walk aimlessly, circling, deranged behavior, colic, press head against solid objects, blindness, and in some cased

consider testing to ensure that the feed is safe for horses. The presence of fumonisins should alert feed manufacturers to monitor ingredients, especially corn, and evaluate the level of corn in horse feeds.

even death can occur.

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Swine

Numerous studies showed that acute fumonisins’ toxicity in

Swine chronically intoxicated with FB1 and FB2 even at low dose shows

swine is linked with pulmonary

nonspecific clinical symptoms such as reduction of daily feed

edema which generally occurs

consumption and body weight gain, lower feed conversion rate and

between 3 and 5 days after

carcass quality, associated with hepatic lesions and overall sickly

the initial consumption of

appearance of the animal..

contaminated feed. Necropsy of swine intoxicated with high doses of fumonisins have shown the occurrence of pulmonary edema which frequently evolves into hydrothorax. The lungs of pigs affected by pulmonary edema did not collapse when removed from the chest, and they increased in size with rounded edges.

D ifferen t

stadiums of pulmon ary

edema syndrome in pigs induced by fumonisins in toxication

1

2 Apathy and

Dog sitting position in

depression at the

order to relieve

beginning of clinical

pulmonary pressure

symptoms of pulmonary edema

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Cyanosis of

4

Progression of respiratory

extremities and

diculties and initiation of

progression of apathy

oral respiration

5 Death of animal due to intense pulmonary edema

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Poultry Nevertheless, of the relative resistance to fumonisins, these can still have negative effects on poultry. These negative effects can be summarized as follows:

The most important immunosuppressive effects Decreased performance

Increased kidney

(weight loss and poor

and liver weights,

feed conversion)

liver necrosis

of fumonisins in poultry are: Reduced thymus weight Reduced immunization against Newcastle disease Reduced macrophage numbers

Reduced egg

Fertility and

production

hatchability of eggs

Decreased phagocytic ability of macrophages, leading to increased susceptibility to bacterial infections

Decreased total white blood cell counts

Reduced

Low exposure levels to FB1 increased

pigmentation

sphinganine to sphingosine ratios in broiler chicks (Ledoux et al., 2003)

Induces thymic cortical thinning, mild bursal follicular atrophy and mild splenic lymphocyte depletion Decreased lymphocyte response to Salmonella gallinarum infection

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Ruminants Ruminants are

Gross and histopathological lesions, as well as

considered less

changes in serum enzymes and biochemistry indicate

sensitive than horses

an impairment of liver and possibly kidney function.

and pigs.

Although fumonisin is poorly absorbed and metabolized by cattle, it induces disturbances in the gastrointestinal tract.

Rumen motility can be slowed, due to increased exposure of the intestinal epithelium to Fumonisins and other mycotoxins.

INVISIBLE LOSSES - SUBCLINICAL EFFECTS Acute mycotoxicosis occurrences are rare events in modern livestock production. However, low mycotoxin doses, which very often not detected, are responsible for reduced efficiency of production and increased susceptibility to infectious diseases.

Nonetheless, a more likely scenario is to find mycotoxins at lower levels interacting with other stress factors leading to subclinical losses in performance, increase in incidence of disease and reduced reproductive performance. For the farmers, these subclinical losses are of greater economic importance than losses from acute effects, which are even more difficult to diagnose.

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The molds They grow on a variety of different crops and foodstuffs including cereals, nuts, spices, dried fruits, apples and coffee beans, often under warm and humid conditions. According to FAO, at least 25% of the world’s food crops are contaminated with mycotoxins, at a time when the production of agricultural commodities is barely sustainable.

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