4.3 Feed and Water Toxicants

Question 1

what are ionophores used for? what are common examples?

Answer 1

Used as coccidiostats and growth promotants
Examples include:
Monensin, Lasolacid, Salinomycin

Question 2

comparative toxicity of ionophores to different species?

Answer 2

Most toxic: Horses
Mid: Cattle, Sheep, Dogs
Least: Chicken, Turkeys

Question 3

Monensin: Mechanism of Toxicity

Answer 3

Mechanisms are not fully explained
Likely sustained Na+-induced Ca++ effect in myocytes Muscle contraction > necrosis

Question 4

How do we diagnose Monensin toxicity?

Answer 4

Serum biomarkers
 increased AST, CK, AP
 Cardiac troponin ❤
 Reduced Ca++ and K+

Chemical Analysis
 Ionophore screen in feed/tissue
 Cattle > 33 ppm, Poultry >110 ppm
 Rapidly metabolized in tissue residues

Question 5

Differentials for Monensin toxicity?

Answer 5

 White muscle disease (selenium deficiency)
 Cardiotoxins (yew, oleander)

Question 6

treatment for Monensin toxicity

Answer 6

 Feed change, supportive care, detoxification, decontamination
 Avoid cardiorespiratory exertion (putting cattle in a chute)

Question 7

Target organs of Monensin toxocity in various species

Answer 7

=>muscle necrosis

Cardiac muscle
Horses Donkeys Cattle

Skeletal muscle
Sheep Pigs Dogs

Question 8

clinical signs of Monensin toxicity in cattle

Answer 8

• Anorexia, decreased milk production
• Mild diarrhea and depression
• Dyspnea, ataxia, death from cardiac failure

Question 9

what factors contribute to acute nitrate/nitrite toxicity in ruminants?

Answer 9

High nitrate intake
 Plants (>1%) and/or water (>1000ppm)

Season and climate
 Some plants have high nitrate content
 More likely in spring (use of nitrate fertilizer), or after frost damage or drought
 Roots take up more nitrate as soil warms
 Reduced photosynthesis slows nitrate utilization

Mismanagement
 Hungry animals eat more
 Reduce proportion of high nitrate components in mix

Question 10

what is the mechanism of nitrate/nitrite toxicity in ruminants? what is the result?

Answer 10

Nitrates (water contamination, young green feed, etc)
>Convert to nitrite (rumen flora)
>Nitrite binds to Fe3+ in heme Oxidation to methemoglobin
>Hypoxia and vasodilation (nitric oxide/NO)
=>Methemoglobinemia

Question 11

clinical and necropsy signs of acute nitrate/nitrite toxicity in ruminants

Answer 11

 Weakness and collapse, ataxia, death
 Acute death, cyanosis, dark brownish blood (variable)
 Nitrate (>20 ppm) in ocular fluids (rapidly degraded)
 Abortions 3-7 days after fetal hypoxia

Question 12

treatment for acute nitrate/nitrite toxicity in ruminants

Answer 12

 IV methylene blue (1 or 2%: 1-10 mg/kg IV)
> Reverses methemoglobinemia

Question 13

prevention of acute nitrate/nitrite toxicity in ruminants

Answer 13

 Monitor feed nitrates, pasture levels, and intake in critical periods
 Safe levels < 0.5%

Question 14

how does salt poisoning occur?

Answer 14

High sodium intake during water deprivation
Precipitated by renewed access to water

Question 15

***what is the mechanism of salt toxicity? what are the dehydration and rehydration phases?

Answer 15

Dehydration phase [water deprivation]
1. Dehydration increases Na+ in plasma - 135 increase to 160+ mEq/L
2. High Na+ by equilibration in astrocytes and CSF
“salty brains”

Rehydration phase
Water moves into the salty brain!
1. Rapid rehydration reduces Na+ concentration in plasma
2. Water influx into astrocytes and CSF [brain edema] because excretion of Na+ is slower
3. Intracranial pressure increases
4. Perfusion decreases - ischemia and necrosis
5. Polioencephalomalacia (grey matter necrosis), especially in pigs

Question 16

clinical diagnostic signs of salt toxocity? lab signs? necropsy signs?

Answer 16

Clinical Signs:
* Circumstantial: recent water restriction and increased salt intake
* Typical CNS signs: dog sitting, wandering, bump into objects, circling,
seizures, opisthotonus, paddling in a coma
* Death within several to 48 hrs

Laboratory signs:
* High Na+ in serum and CSF
* Na+ analysis of feed (or water)

Necropsy signs:
* Polioencephalomalacia
* Eosinophilic meningoencephalitis transiently in pigs

Question 17

how can we manage and prevent salt toxicity?

Answer 17

Treatment
-No effective treatment

Prevention
-Reduce salt intake
-Gradually resupply water

Question 18

Differentials for salt toxicity?

Answer 18

Differentials: insecticide poisoning, pseudorabies, arsenic, Se intoxication, anything causing CNS signs

Question 19

Non-protein nitrogen (NPN) toxicosis mechanism and clinical signs?

Answer 19

Urea, ammonium acetate, ammoniated feeds, etc

NPN > converted to ammonia > amino acids in rumen

Overload causes hyperammonemia Rapid onset salivation, ataxia, muscle spasms, convulsions, death within
hours of access to new feed mix.

Question 20

how can we diagnose non-protein nitrogen toxicosis?

Answer 20

-High rumen pH (8-10) (but samples are unstable)
-Feed analysis

Question 21

how can we treat non-protein nitrogen toxicosis?

Answer 21

-Cold water (slows rumen metabolism)
-5% acetic acid orally before recumbency
>2-6 L for cattle, 0.5-1 L for sheep and goats

Question 22

what are cyanobacteria? when do we encounter them?

Answer 22

• Primitive photosynthetic bacteria
• Blooms under conditions favoring competition with plant algae
• Warm sunny weather (summer and fall)
• Eutrophication (animal wastes, phosphates)
• Water - pH 6 to 9
  Are generally hepatotoxic and/or neurotoxic

Question 23

what are some toxic forms of blue-green algae? what tissue do they affect?

Answer 23

-Microcystis (M. aeruginosa) and Nodularia (N. spumigen) effect liver
-anatoxin produced by anabaena is neurotoxic

Question 24

what is the mechanism of microcystis and nodularia toxicity?

Answer 24

Inhibit protein phosphatases
-Disrupts cytoskeleton leading to endothelial separation in hepatic sinusoids and zonal hemorrhage/necrosis

Question 25

clinical signs of Microcystis (M. aeruginosa) and Nodularia (N. spumigen) toxicity?

Answer 25

-Vomiting in some species, colic, diarrhea (often bloody)
-Sudden death from hepatic encephalopathy

Question 26

Microcystin Hepatotoxicity mechanism?

Answer 26

-Inhibits protein phosphatase 2A
-Cellular hyperphosphorylation
-Cellular injury and necrosis
-Loss of structural associations

Question 27

Anatoxin Neurotoxicity effects?

Answer 27

Anatoxin-a produced by Anabaena (cyanobacteria)
Acute anterior paralysis and sudden death

Question 28

what are mycotoxins? what do they do?

Answer 28

Toxic secondary metabolites produced by fungi
* ~7 groups are important in animal toxicoses (over 400 exist)
* Ranking depends on agricultural practice and climate
* Residues with human risk important to feed producers

=>toxin production depends on various conditions

Question 29

under what conditions do fungi flourish? which are likely to be found in fields vs storage?

Answer 29

Fungi flourish in high moisture conditions
 Field contamination by plant pathogens e.g. Fusarium
 Storage contamination by saprophytes e.g. Aspergillus

Grains (especially corn), nuts or vegetation (pasture, hay)
 25% of world’s crop harvests are contaminated with fungi
 Levels usually below those responsible for overt toxicity

Question 30

Factors affecting mycotoxin production

Answer 30

Plant substrate
 Plants favor selected pathogens and saprophytes
 Composition (e.g. starch)
 Damage (stress, insects, other fungi, etc)

Growth conditions
 Humidity
 Temperature
 pH
 Oxygen

Geographic locations
Type of mycotoxins consumed
Exposure
Animal susceptibility
Feeding systems

Question 31

zearalenone - where is it found? what is it? what animals does it affect? what are the sings/symptoms?

Answer 31

-found in northern corn areas, including Ontario
-estrogenic mycotoxin
-affects pigs > cattle > > poultry
-vulvar hypertrophy in gilts, infertility, rectal prolapse, mammary hypertrophy

Question 32

trichothecenes - where is it found? what is it and what types are there?

Answer 32

found in continental climates with cold winters

-Over 170 structurally related compounds
-Few of these are important as animal toxins, but few are very potent
-Produced by fungi that grow in cool, damp conditions
-Fusarium spp
Type A: T-2 toxin, diacetoxyscirpenol (DAS), etc
Type B: Deoxynivalenol (vomitoxin), etc
Also have type C and D

Fungi proliferate on plants in the field Further fungal growth in feed storage
-Toxins produced under cool moist conditions
 Over wintered grain and forage
 Moisture >15%
 T-2 toxin + vomitoxin @ 6-12°C
 (whereas is Zearalenone 19-20°C)

Question 33

zearalenone diagnosis

Answer 33

Estrogenic lesions or infertility
Pink Fusarium mould contamination of grain, corn Conditions for production (cool, high moisture) Zearalenone analysis
Pigs >1 ppm (gilts) > 3 ppm (sows) > 9 ppm (boars)
Cattle > 12 ppm (heifers)
Poultry (very resistant)

Question 34

zearalenone treatment/prevention?

Answer 34

Withdraw or dilute feed
Divert feed to cattle (not dairy) or poultry
Prevent moisture and fungal contamination

Question 35

trichothecenes clinical signs

Answer 35

**1. Poor growth/production
**2. Feed refusal (or vomition)

3. Irritation of skin and mucosal membranes
4. Cytotoxic to replicating cells @ higher doses
   * Immunosuppression
   * Impaired hematopoiesis

Question 36

what animals are particularly susceptible to fumonisins?

Answer 36

Fumonisins - pigs and horses are particularly susceptible
=>Horses fed mouldy corn

Question 37

what type of toxic effects and clinical effects do fumonisins have?

Answer 37

Hepatotoxic, vasotoxic, and neurotoxic

**Acute porcine pulmonary edema (PPE)
**Cardiotoxic in pigs
-Hepatotoxicity in various species
-Hepatocarcinogenic in rats
-Nephropathy in rats, rabbits, and lambs
-Linked to esophageal cancer in humans

Question 38

what animal is resistant to fumonisins?

Answer 38

poultry

Question 39

what conditions favor fumonisin growth?

Answer 39

Fusarium verticillioides (syn. F. moniliforme)
Toxic mold in warm conditions

Question 40

what is the mechanism of fumosisin toxicity?

Answer 40

fumonisins inhibit ceramide lipid synthesis
=>cause buildup of sphingosine, which causes:
-CNS vasogenic edema
-inhibits Ca++ channels > cardiac failure

Question 41

what are alfatoxins produced by? how can we see them? where? what species do they affect and how?

Answer 41

 Produced by Aspergillus flavus and A. parasiticus
 Blue (AFB) or green (AFG) fluorescence UV
 Mainly on corn, sorghum, peanuts, small grains
 Grow in storage (or in field) in humid, warm conditions
 Highly potent human toxins
 Hepatotoxic, immunosuppressive, and hepatocarcinogenic
 Wide variation in susceptibility among species
 Dogs: chronic hepatopathy (eventual cirrhosis)

Question 42

effects of aflatoxin on the liver?

Answer 42

Acute: hepatic necrosis
Chronic: cirrhosis and cancer

Question 43

what are ochratoxins? how are they produced and what do they do? what species are susceptible or resistant?

Answer 43

 Produced by Aspergillus ochraceus and Penicillium viridicatum
 Nephrotoxic, hepatotoxic, carcinogenic
 Pigs and dogs most susceptible > chickens
> Porcine nephropathy in Denmark
> Consider meat residues (clear in a few weeks)
 Cattle are resistant (toxin degraded in rumen)

Question 44

what are tremorgens? what do they do and what species are susceptible? what are a few examples?

Answer 44

Neuro-excitatory toxins
-Tremors and convulsions if severe
-Sheep, cattle, dogs most susceptible

Penitrem A - Penicillium spp - Tremors in dogs

Roquefortine - P. roqueforti - (walnuts, garbage)

Paspalitrem - Claviceps paspali - Paspalum staggers

Question 45

what is ergot and where is it found? what does it produce? what effects does it have?

Answer 45

-Ergots are sclerotia (dark resting body, mass of hyphal threads) of Claviceps spp
-Grows in various grains Produce toxic ergot alkaloids
Indole alkaloids, lysergic acid, and ergotamine
-Constrict arterial smooth muscle
-Ischemia of extremities
-Exacerbated by cold