Ionophore Toxicosis in Beef Cattle – Frequently Asked Questions

Dr. Michelle Arnold – DVM, MPH UK Ruminant Extension Veterinarian

Heart and lungs from a cow with heart failure due to ionophore toxicosis. The lungs have a wet appearance compatible with pulmonary edema. Photo courtesy of Dr. Jennifer Janes, UKVDL.

Ionophores – what are they and why are they used?
Ionophores are feed additives utilized in the beef industry since 1975 as growth promoting agents and for control of coccidiosis. The approved ionophores for use in cattle in the US include monensin (Rumensin® – Elanco Animal Health; Monovet®90 – Huvepharma), lasalocid (Bovatec® – Zoetis) and laidlomycin propionate (Cattlyst® – Zoetis). Although all ionophores act similarly, this article will focus primarily on monensin as far more information is available due to its longstanding and widespread use in the beef industry.

Technically, monensin is a “monovalent carboxylic polyether ionophore antibiotic” produced by the fungus Streptomyces cinnamonensis. Ionophores are so named because they carry (the Latin root “phor” means carry) “ions” across normally impervious biological membranes, leading to disruption of normal cellular functions and cell death. When properly fed, ionophores beneficially alter the normal rumen microflora (bacteria, protozoa and fungi), resulting in increased efficiency of energy metabolism and improved nitrogen metabolism. In addition, monensin changes the ratio of volatile fatty acids in the rumen, increasing propionic acid production and reducing butyric and acetic acids, a change that ultimately provides more energy through increased production of glucose. Monensin is specifically labeled in beef cattle for 1) improved feed efficiency in mature beef cattle and cattle fed in confinement for slaughter; 2) increased rate of weight gain in stockers, feeders and replacement heifers; and 3) the prevention and control of coccidiosis in all classes of cattle (except veal calves) caused by Eimeria bovis and Eimeria zuernii. In addition to its label claims, feeding monensin to cattle is known to reduce the incidence of bloat, rumen acidosis, and acute respiratory distress syndrome. More information on the use of Rumensin in beef cattle may be found at the following link: https://farmanimal.elanco.com/us/beef/products/rumensin .

Is ionophore intoxication (poisoning) a frequent occurrence?
Not at all! Ionophores are considered safe and effective when used in the approved species receiving the recommended amounts per label directions. Monensin has a relatively wide margin of safety in cattle after a short acclimation period to the drug. Poisoning mostly occurs either from accidental contamination of feed and feed supplements for the wrong species (horses, for example) or errors in feed mixing or product selection resulting in excessively high concentrations in the diets of cattle. At high doses, ionophores affect the heart and skeletal muscle cells, causing cellular degeneration and death. An overdose may cause symptoms ranging from anorexia to severe heart and skeletal muscle damage or sudden death. There is no antidote or specific treatment for ionophore toxicosis except general supportive care. Of primary importance is the recognition of the clinical signs in multiple animals within a group of cattle as potentially feed-related, and to remove suspect feeds or minerals until testing can confirm or deny exposure.

What are the maximum approved feed concentrations of monensin for different classes of beef cattle?
Confusion can easily arise when looking at dosages and units used for ionophores. In general, feedlot cattle dosages are given in grams monensin/ton of complete feed (g/ton) since feedlot cattle in confinement are fed a total ration delivered daily. Feedlot cattle should receive 5-40 grams monensin/ton of complete feed to provide 50-480 mg monensin per head per day. The pasture or dry lot cattle dosage is 50-200 mg monensin per head per day. The methods used to deliver the ionophore include mixed in as a complete feed, mixed and used as a top dress, or offered “free-choice” in a loose mineral, protein or mineral block form. The label concentrations may be expressed in grams/ton or parts per million (ppm) and may include additional instructions to mix the drug with grain.

What are the symptoms of an ionophore overdose?
In cattle, the onset and severity of symptoms depends on the animal’s weight, the amount consumed and if this was the animals’ first time to consume feed containing an ionophore. Symptoms may develop quickly or may be delayed for days to weeks after exposure and include:

Sudden death; cattle are found dead with no symptoms noted previously;
Feed refusal, reduced feed intake or complete anorexia (off feed), usually within 24 to 36 hours after
consuming a high dose (this is considered the most consistent symptom observed); water intake may also be
negatively affected;
Dullness, lethargy, depression;
Diarrhea, signs of abdominal pain (24-48 hours post-consumption);
Weakness, ataxia (stumbling, incoordination, loss of balance), muscular stiffness (associated with higher dosages), muscle tremors;
Difficult, rapid and/or labored breathing, especially with higher dosages;
Recumbency (Down) and death within 3 to 14 days of ingestion of the contaminated feed but potentially 30 days or more after poisoning;

Cattle that appear to recover from the initial overdose may develop heart failure due to the death of heart muscle cells. Heart failure looks similar to pneumonia with difficult, labored breathing due to fluid buildup in the lungs and calves may die suddenly if exercised or stressed. Deaths and/or poor performance can occur for extended periods after exposure depending on the severity of the heart damage and scarring of the heart muscle. Producers with death losses due to a known mixing error should delay filing insurance claims for at least 30 days after a deadly exposure. In addition, the Food Animal Residue Avoidance Databank (FARAD) should be contacted (www.FARAD.org) by a veterinarian for meat witholding information to determine when the remaining animals may be legally sold.

How much monensin is required for intoxication?
The adverse effects of monensin for cattle and other species are well-documented and known to be dose dependent. In addition, the greatest risk of poisoning occurs in cattle not acclimated to an ionophore-containing ration. The monensin LD50 for cattle (the amount of monensin expected to cause the death of 50% of exposed animals) is not firmly established but has a published range by the manufacturer of 21.9-35.8 mg monensin/kg BW (Elanco, 1978). Cattle that survive an acute overdose will generally develop anorexia for several days following the incident so repeated daily intake of a high level of monensin is unlikely. However, the presence of a toxic amount of monensin in feed does not deter consumption when it is first offered.

How much lasalocid does it take for intoxication to occur?
There is relatively little information regarding the toxicity of lasalocid. The recommended dose is 1 mg lasalocid/kg BW and clinical signs of anorexia and diarrhea develop at 10-25 mg/kg BW. Deaths from lasalocid have occurred at 50 mg/kg BW and above. At 50-100 mg/kg BW, muscle tremors have been noted within 3 hours of a toxic dose. Lasalocid deaths occurred between 2-22.5 days after a 50 mg/kg BW dose and within 1-2 days after a 100 mg/kg BW dose.

How much laidlomycin does it take for intoxication to occur?
The Freedom of Information (FOI) summary for laidlomycin (NADA 141-025, 1994) provides some toxic dosage information for laidlomycin in cattle. Cattle offered a dosage 10-50X higher than the approved dosage developed anorexia within 12 hours of the first dose, profuse watery diarrhea within 24 hours of the first dose, weight loss, decreased to absent rumen motility, slow heart rate by day 3, and depression. One animal died four days after the last dose due to cardiac (heart) muscle damage.

How is ionophore toxicosis diagnosed?
A full postmortem examination or “necropsy” at a veterinary diagnostic laboratory is recommended. Cattle that die quickly within the first few days after an overdose may not have obvious abnormalities on necropsy that can be seen with the naked eye but the damage to the heart muscle cells can be seen microscopically. Typical findings include heart and skeletal muscle degeneration that look like pale or yellow areas within the muscle. Secondary problems that develop from heart failure such as wet, heavy lungs, and an enlarged, pale liver are frequently found. In addition to necropsy, samples of the suspected feeds and all feed labels and delivery tickets should be collected and submitted for ionophore analysis. Samples should be taken of all sources of feed and mineral as soon as a problem is suspected and, if possible, from the exact location where the animals were fed. Ionophore intoxication usually involves a recent change in feed or mineral supplementation and generally affects more than one animal. This “change in feed” may be a new batch of feed delivered, new ration formulation, new method of mixing, same ration fed to new group of animals, same ration made by a different feed mill, same ration but in a different form (such as pelleted), or new bag of minerals offered. Unfortunately, samples of feed taken for testing may not represent what the cattle actually ate, especially in cases of incomplete mixing of ingredients or if the suspected feed was from the bottom of the feed bin and new feed has been delivered. It is imperative to interview everyone involved in feeding and mineral supplementation for the past week. Ask what was fed and when, and if any feed refusal was noticed or unusual amount of feed was left in the bunk. Gather as much evidence as possible, fully document this information, and provide it to the veterinary diagnostic laboratory to help guide the investigation. Although it is nearly impossible to determine individual monensin exposure, the heavier and more aggressive animals tend to consume the largest amount of feed and receive the highest doses.

One consistent mistake made by cattle producers is offering a medicated mixing mineral to cattle free-choice. “Mixing minerals” containing ionophores are designed to be mixed in at least 1 pound of non-medicated feed before offering to cattle daily to control intake. In addition, the label clearly states cattle should receive no more than 100 mg/head/day contained in not less than 1 pound of feed for the first 5 days of feeding. “Free choice” products, on the other hand, are formulated specifically to limit intake and reduce the risk of overconsumption. The feeding directions on the label should be followed carefully and all cautions observed. Cattle can eat enough medicated mineral to cause intoxication, especially when offered concurrently with ionophoremedicated feeds. The potential also exists for overconsumption of monensin when a new bag of medicated mineral is offered if cattle are salt-deprived, either due to prolonged periods without access to minerals or if the available mineral has hardened due to excess moisture and is difficult to consume. Additionally, excessive rain on exposed mineral can dissolve and leach away salt, increasing the concentration of the remaining ionophore. Careful use of the correct product, reading label ingredients and recommendations, and feeding in weatherprotected feeders will help prevent problems.

Will analysis of rumen contents for ionophores prove an overdose?
Definitive diagnosis of ionophore toxicosis is not a simple task. Diagnosis is based on a history of exposure to an excessive dosage of ionophore and either sudden death or evidence of heart damage and failure on necropsy. Heart and lungs from a cow with heart failure due to ionophore toxicosis. The lungs have a wet appearance compatible with pulmonary edema. Photo courtesy of Dr. Jennifer Janes, UKVDL. The ionophore concentrations in rumen contents and other tissues are difficult to interpret and, if several days passed between exposure and death, concentrations can be too low to detect. Information about when the animal last ingested monesin and prior daily monensin intake are necessary to interpret the data. Otherwise, the presence of ionophores simply proves it was consumed but does not confirm an overdose.

What if all findings point to ionophore toxicosis but no overdose is found?
One complicating factor that is poorly understood is the interaction of monensin with other compounds (such as tiamulin, oleandomycin, chloramphenicol, erythromycin, sulfonamides, or furazolidone) that can result in clinical monensin toxicosis, despite using the feed additive within the approved range. One hypothesis proposed to explain this increased toxicity is certain antibiotics may delay clearance of monensin by the liver, resulting in its accumulation to toxic levels. In an unusual case published in 1999, macrolide antibiotic residues found in dried distiller’s grains within the feed appeared to affect the otherwise safe levels of monensin, leading to clinical ionophore poisoning. In any case, it is critical to obtain a thorough history regarding all other drugs the animals received concurrently with the suspect feed to make this diagnosis.

Important take-home points:

The greatest risk for intoxication is when cattle receive a feed containing an ionophore for the first time because the rumen microflora are not adapted to the new ingredient. Many products containing monensin require an acclimation period during which cattle should receive no more than 100 mg per head per day for the first 5 days of feeding.
Feed ingredients must be monitored when they are delivered and initially fed, especially when a ration change has been implemented. Rapid recognition of anorexia and diarrhea within 24 hours of the introduction of a new feed or mineral, followed by the prompt removal of the new feed may help avoid more severe consequences and losses.
Implement standard operating protocols for feeding cattle on the farm to reduce the risk of mistakes. Employee training is essential. Do not assume that employees new to feeding cattle know the differences in feed ingredients and the importance of correctly measuring them. Communicate what employees need to do, why it is important, and then follow-up, follow-up, and follow-up to ensure it is done correctly.
Thorough mixing is necessary to ensure the ionophore is evenly distributed throughout the feed. In addition, minimizing the sorting of feed ingredients by cattle is critical to ensure consistent intakes since cattle will pick out (or “sort”) the ingredients they like best and eat those first if given the opportunity.
When offering feed containing ionophores, make sure a free-choice medicated mineral is not available at the same time.
Follow label mixing directions for correct drug delivery when using a medicated mixing mineral rather than offering it free-choice.
It is the producer’s responsibility to read the feed label ingredients to ensure purchase of the correct product prior to offering it to cattle.

Example of Mixing Instructions for a Medicated Feed Supplement:
“Feed at rate of 440 ppm monensin mixed in 0.45 kg of feed”
Conversion: 440 mg monensin/kg supplement * 0.45 kg/pound
= 200 mg monensin in 1 lb feed
The Electronic Code of Federal Regulations regarding all types of drugs in animal feeds may be found at the Code of Federal Regulations website.

In summary, ionophores are an excellent supplement in beef cattle and very safe when fed appropriately according to label directions. There are other possible causes of symptoms resembling ionophore toxicosis in cattle such as from consumption of cardiotoxic (heart damaging) plants (Cassia occidentalis or Coffee senna, Taxus spp., some milkweed species, white snakeroot, mountain laurel, and others), gossypol, and seleniumtoxicosis or deficiency (nutritional myopathy) that cause skeletal and cardiac muscle degeneration and necrosis. Work with your veterinarian to arrive at an appropriate diagnosis.

Source: Ohio State University