Previous - Next
by Sunchai Luxsanakoses
INTRODUCTION
History
Mycotoxins may be produced on bay, cereals, pastures, or fodder, or may be present in constituents used in the manufacture of meals or pelleted animal diets. Some animal diets, especially those containing grain or nuts, may contain several toxigenic species of mould, which may produce a number of mycotoxins having different toxic or pharmacological properties. Under these situations, clinical signs and lesions found In disease outbreaks may not conform to the usual descriptions of outbreaks, or to experimental findings in animals dosed with mycotoxins isolated from pure mould cultures.
Tentative Diagnosis (Confirmation)
History
Clinical signs
Lesions
requires extraction & identification of responsible mycotoxins from suspect foodstuffs.
Treatment
Generally ineffective
But some animals recover if the source of toxin is removed
Others are stunted or die.
CLASSIFICATION OF MYCOTOXINS
Classified according to the main organ system, they affect.;
Hepatotoxins
Nephrotoxins
Neurotoxins
Cytotoxins (Alimentary Tract Toxins)
Estrogenic Mycotoxins
Other Mycotoxins
Discovered by:
Stevens et al. 1960: Turkey H disease outbreak Wannop, 1961; Abrams, 1965: duckling is more susceptible
Asao et al (1963): isolated the Chemical structure & referred to it as "Aflatoxin"
Harley et al (1963): found FBI, FB2, FG1, and FG2 Aflatoxicosis increases the susceptibility of turkeys to candidasis. pasteurellosis and salmonellosis, and of chicks to coccidiosis and Marek's disease: Experimental work has revealed a significant interaction between aflatoxin and vitamin D with respect to bone calcification in chicks, this increasing their vitamin D requirements. (Bird, 1978).
Vitamin A increases mortality rate in Aflatoxin chicks (Bryden et al., 1979)
Affected: Animals:
Poultry
ducks; turkey poults; pheasant
chicks; chickens quail
Mammals
young pigs; pregnant sows;
dogs; calves; cattle; sheep; cats; monkeys; man
Fish
Lab. animals
Cause(s):
Some strains of Aspergillus flavus & most strains of A. parasiticus
Sign(s):
a high mortality
sudden onset
inappetite
dejected appearance
Farm animals:
Other animals:
Chicken:(5)
depression, inappetence, lower growth rates, poor condition, bruising, lowered egg production, fertility, and hatchability, with high mortality. Also, ataxia, convulsion and opisthotonos are common signs.
less plasma testosterone(22)
paralysis & lameness(24)
Turkey poults & ducklings are particularly susceptible. In acute outbreaks, death occunsafter only a short period of inappetence. Subacute symptoms are more usual.
Fish
highly sensitive
1 ppb B1 - cancer in Rainbow trout(5)
Rat
highly sensitive p.(6)
1 ppb B1 - cancer in Fisher rat(5)
Severity ~ Biological Effect of Toxin(3)
Doskges:
Duration of Expose:
Species:
Sheep - highest resistance
Duck - lowest resistance & the most susceptible
breed:
Age:
young animals are more susceptible to acute effect(22)
diet:
dietary protein (11): The effect of aflatoxin is enhanced by a low protein diet.
A low fat diet also: increases the aflatoxin effect
animal's health
individual susceptibility
Type of Toxin
PM Lesion(s):
Target organs(5)
Liver- major
Kidney - minor (in some condition)
Colon - minor (in some condition)
Chich(23)
Testes
Liver
general edema with congested spleen & kidneys marked degenerative changes in the parenchymal liver cells
bile duct proliferation a membranous glomerulonephritis hyaline droplet necrosis some degree of ascites & visceral edema pale & mottled liver with widespread necrosis excessive bile production (common) marked catarrhal enteritis (characteristic) (especisily duodenum).
Diagnosis:
A. flavus may be isolated from feed.
Biological assays for the toxin (duckling/poults).
Chemical assays: fluorescent/chromatographic
techniques.
Suspect: if his topath. shows that hyperplasia of
bile ducts (Common)
Chickens hepatic cells enlarged with some necrotic foci. if feed aflatoxin 25- 15,000 µg/Kg for 8wks the highest B1 residue will be found in liver (muscles)
Swine
if feed aflatoxin 300-500 ug/Kg for 4 months B1
residue can be found ~137 ug/kg in liver but if stop
feed aflatoxin for 2 wks-no liver aflatoxin residue
can be found
FDA (3)
to condemn foods with 15 ppb B1 (6)
Mild inhibitors can control the growth of A.flavus in the feed, i.e.
- 8-Hydroxyquinoline (500 ppm [0.5 gm/kg]) - Gentian violet (500-1500 ppm [0.5-1.5 g/kg]) - Propionic acid (500-1500 ppm [0.5-1.5g/kg]) - Thiabendazole (100 ppm [100 mg/kg])
Fed a high energy, good quality protein diet, increfsed water, and fat soluble vitamins.
Luteoskyrin
Animals Affected: chicken rat
Cause(s): Penicillium islandicum
PM Lesion (s): liver necrosis
Cyclochlorotine
Animals Affected: chicken rat
Cause(s):
Penicillium islandicum
PM Lesion(s): liver necrosis
Rubratoxins
Sources: maize; legume; cereal; peanut kernels; pods; sunflower seeds; bran
Charcteristics: Classification: Rubratoxin A Rubratoxin B
Animals Affected: several spp.
Cause(s):
penicillium rubrum sign(s): several organs & tissues hemorrhage, especialIy - liver
Sterigmatocystin
Sources: Green coffee/moldy wheat/Dutch cheeses Charcteristics: low acute toxicity about 1/10 as potent a carcinogen as B1 Spp. Affected: Lab. animals mice/rats Cause(s): Several spp. of Aspergillus Penicillium luteum Bipolaris sp.
NEPHROTOXINS
Ochratoxin
Sources:
Cereal grains
wheat/Barley/Oats/Corn/Dry beans/
Moldy peanuts/Cheese/Tissues of
swine
Characteristics:
Ochratoxin A-a potent nephrotoxin in
RatslDogs/swine
teratogenic to Mice; Rats, & Chicken embryos
involved in Porcine nephropathy?
Animals Affected: Poultry ducks/chickens Mammals swine/dogs/man(?)
Cause(s): Aspergillus ochraceus & related spp. Penicillium uiridicatum other Penicillium spp.
Sign(s):
3.6 mg/Kg Ochratoxin A causes 5% mortality
rate(4)
54 mg/Kg Ochratoxin B(4)
lowered growth rate
edema of visceral organs
accumulated of uric acid in
kidneys
ureters
heart
spleen
liver
suppress as blood-forming in bone marrow
suppress as lymph formation in spleen
bursa of Fabricius
highest toxicity in broiler (4)
5 ppm Ochratoxin in feed- growth rate
4-8 ppm Ochratoxin in feed-high mortality
rate
4 ppm Ochratoxin in laying hen-ceases egg
production
Citrinin
Sources:
Cereal grains wheat/Barley/Corn/Rice
Charcteristics: a yellow colored compound involved in Porcine nephropathy? lower toxicity than Ochratoxin
Animals Affected:
Mammals
swine/dogs
Lab. animals
Cause(s): several Penicillium spp. several Aspergillus spp.
NEUROTOXINS
Penitrem A
Sources: silage
Characteristics: produces neurological & renal effects
Discovered by: Wilson et al. 1968
Spp. Affected: Cattle sheep horses
Causes(s): Penicillium cyclopium
Sign(s): incoordination syndrome (staggers)
Patulin
Sources: Moldy feed/Rotted apples/Apple juice/Wheat straw residue
Characteristics: carcinogenic in mice found Pexpansum in apple & apple juice
Spp. Affected: Poultry chicken embryo/chickens/quaiI Mammals cattle/cats Lab. animals mice/rats/rabbits Aquatics brine shrimp/guppies/zebra fish larvae
Cause(s): numerous Penicillium spp. numerous Aspergillus spp. Byssochlamys nivea
Citreoviridin
Cause(s): Penicillium citreoviride
Sign(s): directly affects the central nervous system paralysis convulsion respiratory failure cardiac failure death
Miscellaneous Neurotoxins
Cause(S): Claviceps paspali aspergillus fumigatus
Sign(s): nervous disorder: ataxialparesis/apathyl hypersensitivity/frenzy locomotor problems
CYTOTOXINS (ALIMENTARY TRACT TOXINS)
Trichothecenes
T-2 Toxin (Fusariotoxin)
Sources:
Corn/Wheat/Commercial cattle feed/Mixed feeds
Characteristics:
quite toxic to rats/trout/calves
involved in ATA (Alimentary toxic Aleukid) in human
has been implicated in "Yellow Rain" in Southeast
Asia
is not thought to be carcinogenic
is very toxic, but low contamination in foods & feeds
Spp. Affected: Poultry turkey/chickens Mammals swine/cattle/horses/dogs/cats/man Lab. animals mice/rats
Cause(s): Fusarium tricinctum(4) Fusarium spp.
Sign(S):
Poultry:
affect to G1 tract of broiler
1 ppm T-2 causes stomatitis
20 mg/Kg in Laying hen
stomatitis
<<appetite
wt. loss
<< egg production
soft shell
abnormal of hair coat
large doses in chickens cause
oral lesions
large intestine hemorrhage
severe ascites
neurotoxic effects
death
tibial dyschondroplasia (26)
Skin of Rabbits/Rats/& other animals (+Man) severe dermal responses
Cattle:(16) similar to other spp. coagulopathy immunosuppression hematologic changes Iymphatic necrosis or atrophy decreased feed consumption decreased weight gain
Swine:(19) anorexia lethargy posterior weakness/paresis persistent high fever decreased weight gain prominent neutrophilia decreased serum glucose/albumin/alkaline phosphatase increased serum globulin topical exposure can cause systemic effects reduced cardiac output (hypotension) (21) circulatory shock (21)
Treatment Swine superactivated charcoal with magnesium sulfate improved survival times and rates (25)
Diacetoxyscripenai
Sources:
Corn/Wheat/commercial cattle feed/Mixed feeds
Spp. Affected: Poultry turkey/chickens Mammals swine/cattle/horses/dogs/cats/man Lab. animals mice/rats
Neosolaniol
Sources:
Corn/Wheat/Commercial cattle feed/Mixed feeds
Spp. Affected: Poultry turkey/chickens Mammals swine/cattle/horses/dogs/cats/man Lab. animals mice/rats
Nivalenol
Sources:
Corn/Wheat/Commercial cattle feed/Mixed feeds
Spp. Affected: Poultry turkey/chickens Mammals swine/cattle/horses/dogs/cats/man Lab. animals mice/rats
Diacetyinivalenol
Sources:
Corn/Wheat/Commercial cattle feed/Mixed feeds
Spp. Affected: Poultry turkey/chickens Mammals swine/cattle/horses/dogs/cats/man Lab. animals
Deoxynivalenol (DON, vomitoxin)
Sources:
Corn/Wheat/Commercial cattle feed/Mixed feeds
Characteristics: moldy corn toxicosis of swine may have teratogenic effect unlike T-2 toxin, DON contamination in feed is significant
Spp. Affected: Poultry turkey/chickens Mammals swine/cattle/horses/dogs/cats/man Lab. animals mice/rats
Sign(s): vomitting in animals inappetite lack of weight gain digestive disorders diarrhea death
HT-2 Toxin
Sources:
Corn/Wheat/Commercial cattle feed/mixed feeds
Spp. Affected: Poultry turkey/chickens Mammals swine/cattle/horses/dogs/cats/man Lab. animals mice/rats
Fusarenon H
Sources:
Corn/Wheat/Commercial cattle feed/Mixed feeds
Spp. Affected: Poultry turkey/chickens Mammals swine/cattle/horses/dogs/cats/man Lab. animals mice/rats
ESTROGENIC MYCOTOXINS
F-2 Toxin (Zearalenone)
Sources:
Corn/Oats/Barley/Wheat/Sorghum(both fresh and
stored)/Moldy hay/Pelleted commercial feed high moisture corn
Characteristics:
- a potent nonsteroidal estrogen
- one of the Resorcyclic acid lactones (RAL)
- under controlled administration; "zearalanol", a closely related RAL, is widely used in cattle as an anabolic agent
- not highly toxic
- needs 1-5 ppm to cause responses in swine
- can be transmitted to piglets via sow's milk and causes estogenism in young pigs
Spp. Affected: Poultry turkey/chickens Mammals swine/dairy cattle/lambs Lab. animals mice/rats/guinea pigs
Cause(s): Fusarium Spp.(4) primarily from F. graminearium (roseum)
Sign(S)
affect Reproductive system of mammal
Poultry:
Fusarium roseum(4)
swollen & prolapse of poultry's cloaca
bursa of Fabricius enlargement of turkey
25 ppm F-2 causes no effect to chicken
300 ppm F-2/10 days(4)
no effect to growth rate of Leghorn chicken
but found cysts in reproductive tract
Swine:(48) no effect on libido/mating behavior slight increase in sperm abnormalities vulvovaginitis & estrogenic responses in swine
Cattle:(20) abortion
OTHER MYCOTOXINS
Ergot toxin
Sources: flowers or spikelets of cereals (rye) & of grasses perennial rye grass/cocksfoot/timothy/crested dog's tail/oat grass/yorkshire fog
Characteristics: a worldwide disease of farm animals ergot contains a number of alkaloids ergotamine & ergonovine (ergometrine) are the most important alkaloids ergotamine stimulates the central nervous system
Discovered by:
Edwards (1953)
Spp. Affected: cattle swine sheep
Cause(s):
Claviceps purpurea
(ergot)
Sign(s):
Ergotamine: — Weak clonic convulsions followed by depression — lethargy — weakness —ataxia — stupor — paralysis of respiratory center — hypertension —> tone of uterus — death
Ergometrine:
—capillary endothelium damage
— blocking of capillary flow
—vascular stasis
— thrombosis in small arterioles
— dry gangrene
Cattle:
— lameness for 2-6 weeks or longer
— hindlimbs are affected before forelimbs
— high fever
— high pulse rate
— high respiration rate
— swelling & tenderness of fetlock & pastern
joints
— in 1 week, loss of sensation of the affected
area
— dry gangrene at the distal part
— sloughing of distal part
Swine: — lower feed intake — lower weight gain — lack of udder development of sow pregnacy — weak and undersized newborn piglets — low survival rate of the piglets
Sheep: — similar signs to cattle with additional, mouth ulceration
PM Lesion(s): marked intestinal inflammation in sheep
Control: immediate change to an ergot-free diet grazing or topping of pastures to reduce flower head production.
Fescue toxin (Fescue Foot/Tall Fescue Lameness)
Sources: perennial grass
Characteristics: cool season perennial grass in Australia, New Zealand, Eastern & Central USA, France, Italy
Discovered by: Case (1966) and Keyl ea at. (1967)
SDD. Affected: cattle sheep
Cause(s): unidentified, may be related to Acremonium coenophialum, Fusarium spp., and Aspergillus terreus
Sign(s): lameness in one or both hind feet may progress to necrosis of the distal part of the affected limb tail & ears may also be affected with or without lameness.
Lupins Toxin (Mycotic Lupinosis)
sources: sweet lupines
Characteristics: differs from Lupine poisoning (a nervous syndrome caused by alkaloids present in bitter lupines)
Discovered by: van Warmelo et al. (1970)
Spp. Affected: sheep cattle
Cause(s): Phomopsis leptostromiformis
Sign(s): — inappetite —listlessness — photosensitive (sheep) — ketosis (common) — lacrimation (cattle) — salivation (cattle) —jaundice — death occur in 2-14 days in acute case
PM Lesion(s):
— liver—damage, enlarge, orange-yellow, fatty (acute)
— liver - bronze-or tan -colored, firm, contracted in size, distorted and fibrosed
— copious transudates in abdominal, thoracic and pericardial sac
control:
— frequent surveillance of sheep and of lupine fodder material for characteristic black spot fungal infestation, especially after rains
—oral doses of zinc (0.5 9 or more per day) for protection from phomopsin-induced liver in jury in sheep.
REGULATION AND CONTROL
The U.S. Food, Drug & Cosmetic Act: defines food as adulterated if it contains "any poisonous or deleterious substance which may render it injurious to health". (Labuza 1982: Rodricks & Roberts, 1977)
Safe tolerance levels have not been established for any of the mycotoxins. In the absence of tolerances, FDA has set a regulation which apply to all products known to be susceptible to aflatoxin contamination, including animal feeds. In the U.S., the FDA has an action level of 20 ppb (ug/kg) for aflatoxin in susceptible commodities. Since 1984, FDA has relaxed its action level for aflatoxin levels in feed. The new aflatoxin in feed level should not exceed 100 ppb except those for dairy cows, in which the level still should not exceed 20 ppb. The action level for aflatoxin in whole milk, skim milk and low fat milk is 0.5 ppb.
REFERENCES
1. Velthman JR: Reducing the effects of mycotoxins through nutrition. Texas A & M.Feed International, May 1984:33-36.
2. Casarett & Doull's Toxicology. 2nd Ed:104-105.
3. Richardson KE, Nelson LA, Hamilton PB: Effect of dietary fat levels on dose response relationships during aflatoxicosis in young chickens. Poultry science (1987) 66(9) 1470-1478.
4. Shoyinka SVO, Onyekweodiri EO: Clinicopathology of Interaction between Aflatoxin and Aspergillosis in Chickens. Dep Vet Path & Microbiol, Univ, Nsukka, Nigeria. Veterinary Bulletin. 1988 V58 #2. February.
5. Borisova L et al.: Experimental reproduction of aflatoxicosis in broilers. Borisova L, Duparinova M, Alexandrov M, Tacheva T. Dzhurov D, Chotinski D, Tsvetkov A. Tsentralen Veterinarnomed. Inst., Sofia, Bulgaria. Veterinary Bulletin. 1988 V58 # 1. January.
6. Dafalla R. Hassan YM, Adam SKI: Fatty & hemorrhagic liver & kidney syndrome in breeding hens caused by aflatoxin B1 & heat stress in the sudan. Fac Vet Sci, Univ, PO Box 32, KhartoumNorth, Sudan. Veterinary Bulletin. 1987 V57 #12. December
7. Richardson KE, Nelson LA, Hamilton PB: Interaction of dietary protein level in dose response relationships during aflatoxicosis in young chickens. Dep Poultry Sci, State Univ, Raleigh, NG 27695-608, USA Veterinary Bulletin. 1988 V58 # 1. January.
8. The Merck Vet manual. 6th Ed.1287-88 & 1365.
9. Daivi RR, Adlmoyero AA: Toxic effects of aflatoxin B1 in chickens given feed contaminated c A.flavus & reduction Of the toxicity by activated charcoal & some chemical agents. Avian Diseases (28)1 (1984)
10. Clarke Ml, Harvey DG, Humphreys DJ: Vet.Toxicology 2nd Ed.
11. Hamilton PB: Aflatoxicosis in farm animals. Aflatoxin in Maize. A proceedings of the workshop. El Batan, Mexico, April 7-11, 1986: 51 - 57.
12. Hook BS: Effects of T-2 toxin in cattle. Dissertation Abstracts International, B (1988) 48 (10): 28322833.
13. Bonnefoi M, Bezille P. Arvay O. Braun JP, Bars JLE: Economic impact of facial eczema of sheep in Basque country: preliminary study. Revue de Medecine Veterinaire (1988) 139 (5): 489 - 492.
14. Stolla R. Bauer J. Gedek B: Effect of the mycotoxin zearalenone on semen characters in boars. zuchthygiene (1987) 22 (4): 165-172.
15. Pang et al.: The toxicity of T-2 toxin in swine following topical application. Fundamental & applied toxicology (1987) 9 (1) 50-59.
16. Zhao et al.: Study of abortion in dairy cows caused by zearalenone. J. of Vet. Scs. and Tech. (1987) 5:3 - 6.
17. Lundeen GR: Systemic & regional distribution of blood flow during T-2 toxin induced shock in swine. Dissertation Abstracts International, B (1987) 48 (5): 1267.
18. Clarke RN Doerr JA, Ottinger MA: Age related changes in testicular development & reproductive endocrinology associated with aflatoxicosis in the male chicken. Biology of Reproduction (1987) 36 (1): 117-124.
19. Marvan et al.: Aflatoxin B1 residues in the organs of young poultry. Biologizace a Chemizace Zivocisne Vyroby-Veterinaria (1988) 24 (1): 85-92.
20. Okoye JOA, Asuzu IU, Gugnoni HC: Paralysis and iameness associated with afla toxicosis in broilers. Avian Pathology (1988) 17 (3) 731 - 734.
21. Poppenga RH: Effect of therapeutic intervention on pathophysiology, pathology, and survival in rats and swine following acute intravenous exposure to T-2 toxin. Dissertation Abstracts International, B (1988) 49 (1): 54.
22. Lawler EM, shivers JL, Walser MM: Acid phosphatase activity of chondroclasts from Fusarium-induced tibial dyschondroplastic cartilage. Avian Diseases (1988) 32 (2): 240-245.