Category: Toxicology

Scott Fritz, DVM, ABVT Toxicologist Beef Cattle Institute Kansas State University  Scottfritz@vet.k-state.edu

Sources 

Feed, Protein Tubs, Fertilizer-contaminated water 

Mechanism 

Rumen urease cleaves urea making ammonium, that reaction causes the rumen pH to climb.  At pH >8, the reaction selects for ammonia that is absorbed and transported to the liver.  The liver’s ability to metabolize ammonia is overwhelmed leading to hyperammonemia. 

Signs 

Rapid onset (20-60 minutes) of uneasiness, bloat, dyspnea, recumbency, paddling, cyanosis, and death.  The rapid progression from consumption to death precludes the formation of any reliable lesions.  Rumen pH will typically remain elevated for ~24, pH paper is a cheap and effective way for in-field evaluation. 

Treatment 

Treatment is based on lowering the pH and diluting the urea concentration.  The most effective way to accomplish this is a rumen infusion of acetic acid (vinegar) and cold water.  Animals should be triaged with treatment directed towards clinical animals that are not yet recumbent.  Survivors generally have no lasting effects. 

Diagnosis 

Post-mortem diagnosis is based on ammonia concentrations in ocular fluid as well as rumen pH.  Rumen content should be frozen ASAP because the ammonia will volatize off the sample. 

Links 

• https://www.ksvdl.org/
• https://www.ksvdl.org/testing/submission-forms/Bovine_Submission_Form_091622.pdf
• https://www.ksvdl.org/reports/december_2017/ruminant_toxicosis.html

Scott Fritz, DVM, ABVT Toxicologist Beef Cattle Institute Kansas State University  Scottfritz@vet.k-state.edu

Sources 

Primarily a water deprivation syndrome – cattle can consume a significant amount of salt if fresh water is available.  There are reports of mineral-starved cattle overeating mineral supplements with sodium used as an intake limiter. 

Mechanism 

As animals become dehydrated, the sodium concentration in the brain increases.  The problem is upon rehydration, water follows the sodium into the brain resulting in cerebral edema and death to neurons. 

Signs 

Clinical signs are the same for lead poisoning and polioencephalomalacia and rooted in the central nervous system.  Blindness is a hallmark of the syndrome and can help rule out causes of neurologic disease in cattle.  Ataxia, head pression, recumbency, and death are also associated with the progression of clinical signs. 

Treatment 

The classic therapy for polio cases is injectable thiamine.  Thiamine is a general neuro-protectant but is less effective in water deprivation cases than polio and lead encephalopathy.  Slow rehydration of affected animals is the best approach.  This can be a challenge on a herd basis and veterinarians and producers are often forced to get creative.  Unlimited access to water will precipitate clinical signs and IV fluid therapy is not practical.  Allowing water to run on a flat surface and forcing animals to drink slowly is ideal.  Fluid deficits should be corrected over 12-24 hours. 

Diagnosis 

Diagnosis is based upon clinical signs, lack of a response to thiamine, characteristic lesions in the brain, and elevated brain sodium levels.  It is important to submit both fixed and fresh brain in these cases as formalin-fixed brain is useless for sodium evaluation. 

Links 

• https://www.ksvdl.org/
• https://www.ksvdl.org/testing/submission-forms/Bovine_Submission_Form_091622.pdf

Scott Fritz, DVM, ABVT ToxicologistBeef Cattle Institute Kansas State University  Scottfritz@vet.k-state.edu

Sources 

Alfalfa is the most common source of phytoestrogen exposure in the US.  Other clover species can contribute to the total exposure. 

Mechanism 

Phytoestrogens bind to estrogen receptors in the animal leading to multiple effects. 

Signs 

The most economically important clinical sign associated with phytoestrogens is infertility.  This is especially true in pre-pubescent animals that are exposed and can lead to life-long infertility by disrupting the estrogen-influenced maturation process.  Prolapses have also been associated with feeding high levels of phytoestrogens.  Phytoestrogens do not cause abortion. 

Treatment 

Remove the suspect source. 

Diagnosis 

Phytoestrogen evaluation of suspect feed source.  Clinical improvement following removal. 

Links 

• https://www.ksvdl.org/
• https://www.ksvdl.org/testing/submission-forms/Bovine_Submission_Form_091622.pdf

Scott Fritz, DVM, ABVT Toxicologist Beef Cattle Institute Kansas State University  Scottfritz@vet.k-state.edu

Sources 

• Plants are typically fertilized, and drought-stressed, occasionally herbicide-treated plants can become more palatable and cause problems 
• Plants (Johnson grass, corn stalks, Sudan grass), water (especially with fertilizer contamination) 

Mechanism 

Rumen reduces nitrate to nitrite.  Nitrite reduces the iron in heme forming methemoglobin that can’t carry oxygen – the affected animal become anoxic.  Clinical signs will occur at 30-40% methemoglobin, death can occur when methemoglobin is >70%. 

Signs 

Rapid onset (30 minutes to hours) of weakness, bloat, ataxia, recumbency, cyanosis, and death.  The rapid progression from consumption to death precludes the formation of any reliable lesions.  Pregnant animals that survive the acute disease may abort 3-7 days after exposure.   

Treatment 

Methylene blue is the traditional antidote administered at 10 mg/kg of a 1% solution.  There are withdrawal concerns for the use of methylene blue due to it being a potential carcinogen, FARAD should be consulted.  Remove the suspect source. 

Diagnosis 

• Brown discoloration of venous blood.  Serum is a good antemortem sample, ocular fluid is the best post-mortem sample.  Rumen content is not a good post-mortem sample as the rumen microbes will continue to degrade nitrate.  Methemoglobin rapidly decays after collection so its diagnostic utility is limited. 
• 1% nitrate in forage can result in acute deaths, 0.5% nitrate feed should not be fed to pregnant animals.  100 ppm in water can result in clinical signs.  Laboratories that do feed and water analyses use different units to report the nitrate content, these units are different and it is imperative to recognize the differences.

 Links 

• https://www.ksvdl.org/
• https://www.ksvdl.org/testing/submission-forms/Bovine_Submission_Form_091622.pdf
• https://www.ksre.k-state.edu/news/stories/2022/08/cattle-chat-toxic-pastures.html
• https://www.iowabeefcenter.org/information/IBC50.pdf

Scott Fritz, DVM, ABVT Toxicologist Beef Cattle Institute Kansas State University  Scottfritz@vet.k-state.edu

Sources 

Mycotoxins are secondary fungal metabolites that are produced by mold that colonizes damaged grains.  Grains are the most common source, but occasionally certain forages can also be an issue. 

Mechanism 

There are only a few mycotoxins with recognized clinical effects, FDAs guidance tables are presented here. 

Mycotoxins and Regulatory Limits 

• CVM focuses on 5 major mycotoxins in the U.S.: 
• Action levels – aflatoxins – Compliance Policy Guidance Manual Section 683.100 
  • Aflatoxin contamination has legal requirements for the sale of commodities 
• Guidance levels – fumonisins 
• Advisory levels – vomitoxin (DON) 
• No action, guidance or advisory levels for ochratoxin A or zearalenone have been established by the FDA in animal feeds (these 2 mycotoxins are handled on a case-by-case basis. 

Action levels for total aflatoxins in livestock feed 

Class of Animals	Feed	Aflatoxin Level
Finishing beef cattle	Corn and peanut products	300 ppb
Beef cattle, swine or poultry regardless of age or breeding status	Cottonseed meal	300 ppb
Finishing swine over 100 lb.	Corn and peanut products	200 ppb
Breeding cattle, breeding  swine and mature poultry	Corn and peanut products	100 ppb
Immature animals	Animal feeds and ingredients, excluding cottonseed meal	20 ppb
Dairy animals, animals not listed above, or unknown use	Animal feeds and ingredients	20 ppb

Food and Drug Administration guidance levels for fumonisins in animal feeds.
Mycotoxin		Use
Total fumonisin	5 ppm (1 ppm)  no more than 20% of diet)	Equids (horses, mules, donkeys) and rabbits
	20 ppm (10 ppm)   (no more than 50% of diet)	Swine and catfish
	30 ppm (15 ppm)  (no more than 50% of diet)	Breeding ruminants, breeding poultry and breeding mink
	60 ppm (30 ppm)  (no more than 50% of diet)	Ruminants older than three months being raised for slaughter and minks raised for pelt production
	100 ppm (50 ppm)  (no more than 50% of diet)	Poultry being raised for slaughter
	10 ppm (5 ppm)  (no more than 50% of diet)	All other species or classes of livestock and pet animals

Advisory levels for vomitoxin (DON) in livestock feed 

Class of Animal	Feed Ingredients &  Portion of Diet	DON Levels in Grains or Grain By-products and Complete Diet**
Ruminating beef and feedlot cattle older than 4 months	Grain and grain by-products*	10 ppm (10 ppm)**
Ruminating dairy cattle older than 4 months	Grain and grain by-products not to exceed 50% of the diet*	10 ppm (10 ppm)**
Ruminating beef and feedlot cattle older than 4 months, and ruminating dairy cattle older than 4 months	Distiller’s grains, brewers grains, gluten feeds, and gluten meals*	30 ppm (10 ppm beef/feedlot)**     ( 5 ppm dairy)**
Chickens	Grain and grain by-products not to exceed 50% of the diet	10 ppm (5 ppm)**
Swine	Grain and grain by-products not to exceed 20% of the diet	5 ppm (1 ppm)**
All other animals	Grain and grain by-products not to exceed 40% of the diet	ppm (2 ppm)**
*88 percent dry matter basis                ** complete diet figures shown within parentheses

Zearalenone: there are no FDA guidelines for Zearalenone.

Class of Animal	hyperestrogenism	anestrous	infertility
Ruminating beef and feedlot cattle younger than 6 months	>1 ppm	3 ppm	12 ppm
Chickens	>1 ppm	3 ppm
Swine	>1 ppm	3 ppm
All other animals	>1 ppm	3 ppm

• Produced by Fusarium sp. (primarily F. graminearum) 
• Common substrates are corn, wheat, barley, occasionally oats 
• Production favored by high humidity and low temperatures 
• Estrogenic mycotoxin, swine most susceptible – vulvar swelling in gilts 
• Toxicity related to reproductive system 
• No FDA action, advisory or guidance levels established for zearalenone in US feed 

Links

• https://www.ksvdl.org/
• https://www.ksvdl.org/testing/submission-forms/Bovine_Submission_Form_091622.pdf
• https://www.world-grain.com/articles/11232-ksu-vet-urges-livestock-producers-to-lookout-for-mycotoxins

Scott Fritz, DVM, ABVT Toxicologist Beef Cattle Institute Kansas State University  Scottfritz@vet.k-state.edu

Sources 

Batteries, paint, older oils and greases, some solders, multiple others. 

Mechanism 

Lead has a variety of effects on different biochemical processes in the body.  Generally, lead binds sulfhydryl groups deactivating some enzymes, lead competes with calcium ions replacing calcium in bone and altering conduction in nerves and muscle, lead also alters vitamin D metabolism and interferes with GABA activity in the CNS. 

Signs 

Clinical signs vary by species.  In ruminants, acute lead exposures cause neurologic signs.  Blindness is maybe the most recognizable and reasonably consistent sign.  Other clinical signs include depression or hyperesthesia, ataxia, seizures, aggression, head pressing, muscle fasciculations, and death. Gastrointestinal signs including bloat and diarrhea may be appreciated. 

Treatment 

The classical antidote for lead poisoning in large animals is Ca-EDTA.  Ca-EDTA can liberate lead from bone causing an increase in blood lead and worsening clinical signs.  Chelation therapy in food animals is not recommended for multiple reasons including poor response to treatment, significant supportive care, and significant residue issues.  In addition, there are no FDA-approved antidotes for food animals, thus, FARAD should be consulted prior to use.  Regulations regarding lead exposure in food animals varies by state.  The state veterinarian should be contacted, and some states will quarantine entire herds until blood lead concentrations drop below specified thresholds. 

Diagnosis 

Diagnosis is heavily dependent upon elevated concentrations of lead in the body.  Ante-mortem testing is easily accomplished with whole blood.  Postmortem sampling should include liver and kidney lead concentrations.  Histologically, lead exposure can cause polioencephalomalacia, it is important to consider water deprivation/salt poisoning, and elevated dietary sulfur in clinical cases. 

Links 

• https://www.ksvdl.org/
• https://www.ksvdl.org/testing/submission-forms/Bovine_Submission_Form_091622.pdf
• https://www.merckvetmanual.com/toxicology/lead-poisoning/lead-poisoning-in-animals

Scott Fritz, DVM, ABVT Toxicologist Beef Cattle Institute Kansas State University Scottfritz@vet.k-state.edu

Sources 

• Water: surface water (ponds especially in late fall or drought years) in some areas of the country and ground water (wells) in others. 
• Feed: Some co-products are recognized sources like DDGs, molasses, etc. 
• Poultry litter 

Mechanism 

Dietary sulfur is converted by the rumen microbes to hydrogen sulfide gas.  H2S is eructed and inhaled and probably absorbed across the rumen wall.  Hydrogen sulfide is a systemic poison that interrupts cellular metabolism.  Tissue with high energy demand, like the brain, are first affected.   

Signs 

Classical clinical signs include ataxia, blindness, and head pressing.  These typically occur 1-4 weeks after starting cattle on a high-sulfur diet. 

Treatment 

Thiamine is the treatment of choice for polio cases.  Corticosteroids, NSAIDs, and diuretics have been recommended but their efficacy is unclear, and the adverse effects of their use may outweigh any benefit they have. 

Diagnosis 

Response to thiamine administration is a strong diagnostic indicator.  Histologic lesions are identical to those caused by lead toxicosis and water deprivation/sodium ion toxicosis.  Brain sodium and liver and kidney lead concentrations should be analyzed to rule out these other causes.  Thiamine has shown to be beneficial in cases of lead encephalopathy. 

Links 

• https://www.ksvdl.org/
• https://www.ksvdl.org/testing/submission-forms/Bovine_Submission_Form_091622.pdf
• https://www.merckvetmanual.com/nervous-system/polioencephalomalacia/polioencephalomalacia-in-ruminants?query=pem

Scott Fritz, DVM, ABVT Toxicologist Beef Cattle Institute Kansas State University Scottfritz@vet.k-state.edu

Sources 

• CCA (chromated copper arsenate) treated lumber, especially after burning, cattle seem to find the ashes palatable. 
• Arsenic-containing insecticides

Mechanism 

Most heavy metals exert their toxic effects by substitution for other metals.  Arsenic is no different.  Trivalent arsenicals interrupt the TCA cycle while pentavalent arsenicals uncouple oxidative phosphorylation.  Both mechanisms interrupt cellular respiration and produce an energy deficit at the cellular level.  Rapidly dividing cells and those with a high energy demand are first affected. 

Signs 

Clinical signs and risk are heavily dependent upon the valence of the arsenic involved.  Generally, clinical signs are severe and associated with the gastrointestinal system.  Colic, weakness, and diarrhea, often hemorrhagic, are common.  Sever neurologic signs can predominate in acute exposures to readily available sources.  Ataxia, staggering, recumbency are common in these cases. 

Treatment 

The classic antidote for arsenic poisoning is dimercaprol in companion animals but is not overly effective after clinical signs are observed so it’s use in clinical cases is limited.  Thioctic acid is more effective in cattle but is not approved for use in food animals.  FARAD should be consulted if used.  Excretion is rapid and, unlike lead, arsenic is readily cleared after exposures. 

Diagnosis 

Diagnosis is heavily dependent upon elevated concentrations of arsenic in liver and kidney.  Both organs should be submitted and it is important to recognize that given the rapid excretion of arsenic, animals that live for long periods after exposure may not have identifiable concentrations in these organs.  Diagnosis can be supported by histologic examination of tissues, especially the kidney and gastrointestinal tract.  Suspect material can also be analyzed. 

Links

• https://www.ksvdl.org/
• https://www.ksvdl.org/testing/submission-forms/Bovine_Submission_Form_091622.pdf
• https://www.merckvetmanual.com/toxicology/arsenic-poisoning/inorganic-arsenical-toxicosis-in-animals