Monensin toxicity in cattle

Monensin has been tested to determine its toxicity and safety in cattle. Single dose acute toxicity and signs associated with toxicity were determined by oral gavage, 7-d oral gavage and feeding experiments with high concentrations of monensin in feed. Oral feeding studies indicated a near complete anorexia resulting from intake of sublethal amounts of monensin. In these cases, cattle recovered from the insulting dose and resumed growth and feed intake. In long-term chronic feedlot, pasture supplement, and reproduction safety studies conducted with monensin administered in the feed, the high concentrations caused cattle to show signs of mild monensin intoxication. Mortality resulted from feeding groups of cattle large quantities of monensin in small quantities of feed. Furthermore, these studies have demonstrated no detrimental effects upon reproduction. Collectively, these studies indicate that the greatest risk of intoxication occurs when cattle first receive a feed containing monensin. Mixing errors and misuse situations under actual use conditions have resulted in cases of cattle mortality. In most cases the mortality was predictable based upon the exposure in controlled studies.     

Comparative toxicology of monensin sodium in laboratory animals

The toxicology of monensin has been studied in several laboratory animal species. There was considerable species variation in acute oral LD50 values. The consistent signs of acute toxicity were: anorexia, hypoactivity, skeletal muscle weakness, ataxia, diarrhea, decreased weight gain and delayed deaths. The 3-mo study in rats fed diets containing 0, 50, 150 or 500 ppm monensin resulted in no effects at the lowest dose level, slight reduction of body weight gain in the middle-dose group and severe depression in body weight gain, skeletal and cardiac lesions, and deaths in the highest dose group. The 3-mo study in dogs given daily oral doses of 0, 5, 15 or 50 mg/kg monensin resulted in no effects at the lowest dose level. Dogs in the 15 and 50 mg/kg groups developed, during test wk 1 to 4, anorexia, weakness, ataxia, labored respiration, body weight loss, increased serum muscle enzyme values, severe skeletal muscle degeneration and necrosis with less severe heart lesions and deaths. Mice fed diets containing 0, 37.5, 75, 150 or 300 ppm monensin for 3 mo had reduced body weight gain in all test groups but no other physical signs. Serum creatine phosphokinase (CPK) values were increased in mice in the two highest dose groups and minimal heart lesions were found in the highest dose group. Dogs given daily oral doses of 0, 1.25, 2.5, 5 or 7.5 mg/kg monensin for 1 yr survived with no evidence of toxicity in the two lowest dose groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monensin poisoning in horses - an international incident

Several hundred Michigan horses were accidentally exposed to varying levels of monensin. Severity of effects was proportional to the level of feed contamination; sudden death resulted on at least two premises. Acute signs of cardiovascular impairment occurred on one premises having received feed containing over 200 grams of monensin per tonne. Gross and histological postmortem lesions consisted of acute myocardial necrosis. Although only circumstantially confirmed, investigations led to the suspicion that the source of poisoning was a ration formulation error in a feedmill in southwestern Ontario. Concern over possible undetected heart damage in exposed horses led to clinical monitoring on one farm over a period of several months. Electrocardiographic and serum enzyme monitoring were used soon after the incident to implicate exposure in some horses; they were poor prognostic indicators. Applicable legislation, the cooperative role of government departments, and legal implications relative to potential prosecution and lawsuits arising from sale of contaminated feed between Canada and the USA are summarized.     

Oxidative monensin metabolism and cytochrome P450 3A content and functions in liver microsomes from horses, pigs, broiler chicks, cattle and rats

The oxidative metabolism of monensin, an ionophore antibiotic extensively used in veterinary practice as a coccidiostat and a growth promoter, was studied in hepatic microsomal preparations from horses, pigs, broiler chicks, cattle and rats. As assayed by the measurement of the amount of the released formaldehyde, the rate of monensin O-demethylation was nearly of the same order of magnitude in all species, but total monensin metabolism, which was estimated by measuring the rate of substrate disappearance by a high-performance liquid chromatography (HPLC) method, was highest in cattle, intermediate in rats, chicks and pigs, and lowest in horses. When expressed as turnover number (nmol of metabolized monensin/min nmol cytochrome P450-1), the catalytic efficiency (chick > cattle > pig approximately rat > horse) was found to correlate inversely with the well known interspecies differences in the susceptibility to the toxic effects of the ionophore, which is characterized by an oral LD50 of 2-3 mg/kg bodyweight (bw) in horses, 50-80 mg/kg bw in cattle and 200 mg/kg bw in chicks. Chick and cattle microsomes also displayed both the highest catalytic efficiency toward two P450 3A dependent substrates (erythromycin and triacetyloleandomycin) and the highest immunodetectable levels of proteins cross-reacting with anti rat P450 3A1/2. Further studies are required to define the role played by this isoenzyme in the oxidative biotransformation of the drug in food producing species.     

Long‐term assessment of horses and ponies post exposure to monensin sodium in commercial feed

Reasons for performing study: Acute monensin intoxication in equids is well described; however, the long‐term effects of sublethal intoxication and ability to return to previous use are less well understood. Long‐term observations may allow improved estimation of prognosis in cases of sublethal intoxication. Objectives: To assess horses and ponies exposed to sublethal amounts of monensin for evidence of chronic sequelae and ability to return to prior/intended use. Methods: Twenty‐nine horses and 8 ponies were assessed utilising serum biochemistry, treadmill exercise stress testing, electrocardiography, and pre‐ and post exercise echocardiography ≥6 weeks after ingestion of monensin‐contaminated feed. Animals with evidence of monensin‐induced cardiomyopathy were re‐examined after a period of rest of ≥11 months. Follow‐up information was obtained by owner telephone interview ≥52 months after exposure. Results: During resting echocardiography, 11 animals had reduced/low‐normal left ventricular fractional shortening (FS); an increase in FS in 8 of these animals was measured ≥11 months later. Six animals had reduced or low‐normal FS during post exercise echocardiography. Two horses had ventricular premature depolarisations during exercise. Follow‐up information was available for 35 animals: 21 returned to athletic/reproductive use, 13 were retired immediately and one died. Mean FS increased significantly (P<0.001) between initial and second examination in 15 animals that underwent resting echocardiography on 2 occasions. Conclusions: Some equids exposed to sublethal doses of monensin may not develop permanent myocardial disease and a return to athletic/reproductive use is possible. Potential relevance: Exercise stress testing, echocardiography and electrocardiography may be useful for detection and monitoring of cardiac dysfunction in equids exposed to monensin and determining whether a return to athletic/reproductive use is possible.     

Administration of monensin in self-fed (salt limiting) dry supplements or on an alternate-day feeding schedule

Two series of trials were conducted to evaluate alternative methods of administering monensin to pasture cattle. In a series of five trials, monensin was incorporated into supplements at 440 mg/kg to provide an average intake of 200 mg X head-1 X d-1 for growing cattle on pasture. Comparisons were made between daily and alternate-day feeding of the supplements. A control treatment consisting of unmedicated supplement fed daily also was included. Monensin at 200 mg/d and 400 mg on alternate days increased gain by .077 (P less than .01) and .082 (P less than .01) kg/d above control-cattle gains (.54 kg daily). Nine pasture trials were conducted to compare the effectiveness of monensin in increasing the daily gain of growing cattle when hand-fed daily in a supplement or self-fed in supplements that contained salt to regulate supplement intake. Desired supplement intakes were approximately .454 kg X head-1 X d-1 in six trials, .68 kg/d in one trial and 1.81 kg/d in two trials. Monensin produced gain increases of .09 kg daily (P less than .01) with both feeding systems. The daily gains of cattle that were hand-fed and self-fed were equal (P greater than .10). Self-fed treatments containing monensin required fewer changes in salt level than self-fed treatments not containing monensin, and the salt levels required to limit intake were generally 25 to 50% lower when monensin was in the supplement.     

Animal nutrition for veterinarians--recent cases of clinical disorders in horses after intake of ionophore-containing feed

Anamnesis and clinical signs of horses form five different stables after ingestion of ionophores are reported and techniques of feed examination are described. Within a few hours or days after feeding of new types or batches of concentrates horses fell ill. They showed colic-like symptoms with intense sweating and ataxia. Most of the sick animals died within a short time span. Samples of the concentrates were analysed and different types and amounts of ionophores were detected. In four cases contamination by monensin in concentrations of less than 5 mg to 679 mg/kg feed were found. One feed sample contained monensin (8.8 mg/kg feed) as well as salinomycin (67.3 mg/kg feed). In one case lasalocid (7.9 mg/kg feed) was present. One horse from the stable where animals had obtained concentrates containing monensin (679 mg/kg feed) was necropsied. Typical signs of monensin intoxication with severe myocardial degeneration were found. Veterinarians should be alert to this rare but severe intoxication of horses.     

Milk residues and performance of lactating dairy cows administered high doses of monensin

Milk residues and performance were evaluated in lactating cows that were fed up to 10 times the recommended dose of monensin. Following an acclimatization period of 14 d, during which cows were fed a standard lactating cow total mixed ration containing 24 ppm monensin, 18 lactating Holstein dairy cows were grouped according to the level of feed intake and then randomly assigned within each group to 1 of 3 challenge rations delivering 72, 144, and 240 ppm monensin. Outcome measurements included individual cow daily feed intakes, daily milk production, body weights, and monensin residues in composite milk samples from each cow. There were no detectable monensin residues (< 0.005 microg/mL) in any of the milk samples collected. Lactating cows receiving a dose of 72 ppm monensin exhibited up to a 20% reduction in dry matter intake, and a 5% to 15% drop in milk production from the pre-challenge period. Cows receiving doses of 144 and 240 ppm monensin exhibited rapid decreases in feed intake of up to 50% by the 2nd d and milk production losses of up to 20% and 30%, respectively, within 4 d. Lactating cows receiving up to 4865 mg monensin per day had no detectable monensin residues (< 0.005 microg/mL) in any of the milk samples collected. Results of this study confirm that food products derived from lactating dairy cattle receiving monensin at recommended levels are safe for human consumption.     

Effect of monensin on the performance of cattle on pasture or fed harvested forages in confinement

Three series of trials were conducted to evaluate the effect of monensin on the growth performance of cattle. Twenty-four trials were conducted to evaluate the addition of monensin at 200 mg/d to limited quantities of supplemental concentrate for growing cattle grazing pastures. The pastures ranged from dormant end-of-the-season grasses and crop residues to lush green pastures, and were located in several different states. Pasture plus supplement supported gains of control cattle (without monensin) of .24 to .96 kg, with an average of .56 kg/d. The addition of 200 mg monensin to the supplement increased daily gain in all 24 trials by an average of .09 kg daily (+16.3%). Eleven trials were conducted with monensin and energy supplements fed at .907 kg.- head-1 X d-1 to growing cattle grazing growing, nondormant pastures for an average period of 117 d. Each trial was designed to compare the performance of unsupplemented cattle, cattle fed a supplement and cattle fed a supplement with monensin. Cattle on pasture gained .50 kg daily. Supplement feeding increased average daily gain by .09 kg and the addition of monensin to the supplement further increased gain by .09 kg, for a total increase of .18 kg (34.2%). The efficiencies with which supplemental feed was converted to extra gain (kg supplement/kg gain) for the supplement-only and the monensin treatment groups were 10.1:1 and 5.0:1, respectively. In a series of 12 trials, monensin was added at a level of 33 mg/kg air-dry diet to limited quantities of supplemental feed for cattle fed harvested forages in confinement. All trials compared monensin feeding with a nonmedicated control treatment. Hay was fed in 8 of the 12 trials, fresh-cut green-chop in two trials and ensiled corn stover and ensiled milo stover in one trial each. Monensin reduced feed intake by -3.1%, improved average daily gain by .09 kg (+14.4%) and improved feed efficiency by 15.3%.     

Pathologic changes associated with experimental lasalocid and monensin toxicosis in cattle

The acute toxicity of lasalocid and monensin was studied in 36 Holstein steers. The cattle were given (orally) a single dosage of lasalocid (1, 10, 50, or 100 mg/kg of body weight) or monensin (25 mg/kg of body weight) or rice hulls. Animals were observed once a day until they died or were euthanatized at 32 days after the dose was given. All cattle were necropsied. Heart, kidney, adrenal gland, liver, spleen, pancreas, lungs, brain, sciatic nerve, skeletal muscle, small intestine, large intestine, and rumen tissue sections, stained with hematoxylin and eosin, were studied microscopically. Lasalocid was lethal at dosages of 50 and 100 mg/kg, and monensin was lethal at the dosage given (25 mg/kg). Cattle dying of lasalocid and monensin toxicoses had gross and microscopic lesions consistent with cardiomyopathy. Dilated heart or petechial and ecchymotic hemorrhages were observed with both drugs. Microscopically, multifocal areas of myocyte necrosis were observed. Those cattle that died within 3 days of dosing with either drug had a marked degranulation of pancreatic acinar cells. Changes were not observed in any other tissues.     

Biochemical studies on the fate of monensin in animals and in the environment

Extensive studies have been conducted with monensin in target animals and laboratory animals to determine monensin concentrations in tissues, route of elimination, metabolism and pharmacokinetics of monensin. These studies indicate that monensin administered orally is absorbed, extensively metabolized, excreted in the bile and eliminated in the feces by the several species examined. Monensin did not accumulate in the tissues of orally dosed animals. When fed to cattle and chickens according to recommended practices, monensin was not detected (less than .05 ppm) in edible tissues. Environmental studies indicate that monensin is biodegradable in manure and soil.     

An epizootiologic study of anthrax in Falls County, Texas.

In June and July, 1974, an anthrax epizootic in Falls County, Texas, resulted in the death of 236 animals (228 cattle, 5 horses, 2 mules, and 1 pig) on 48 premises. Death rates were highest for horses (18.2%) and bulls (16.8%). The epizootic was apparently precipitated by drought, and infection appeared to be the result of ingesting intrinsically contaminated soil and grass. Human illness was not associated with the epizootic.     

Managing lead exposure and toxicity in cow-calf herds to minimize the potential for food residues.

Lead poisoning is commonly diagnosed in cattle. In this study, 3 groups of cattle from different herds accidentally exposed to discarded lead batteries on pasture were intensively studied to determine the extent and severity of exposure. The losses from acute death due to lead toxicity were substantial in all the 3 study groups at 12%, 17%, and 4%. Blood samples were taken from all cattle around the time of the first diagnosis and then later in 2 of the 3 herds to monitor the change in lead concentrations over time. Asymptomatic lead toxicosis was observed in these herds. In these 3 groups, between 4% and 12% of asymptomatic cattle had blood lead concentrations consistent with acute lead poisoning (> 0.35 ppm), and between 7% and 40% of these asymptomatic animals were in the high-normal range (0.1-0.35 ppm). Because of the consistently high number of asymptomatic cattle with elevated lead levels, all cattle potentially exposed to a lead source should be tested before sale or slaughter to minimize the entry of lead into the food chain. The blood lead concentrations, which were monitored for months after the initial diagnosis, decreased slowly after the cattle were removed from the lead source. The prolonged retention of lead may be due to continued release and absorption of lead from metal particles in the reticulum or rumen. The mean reduction in the lead level was 0.046 ppm (95% CI, 0.017-0.075 ppm) every 30 days for these 2 herds. Using a single-component exponential model, the half-life of lead in the animals retested from Herds 1 and 2 was highly variable. The median half-life was 63 days (interquartile range, 34-107 days). One out of 8 pregnant heifers with high blood levels had a stillborn calf. There were no abortions or calf mortalities in this group. Blood samples were'collected from the calves around the time of birth. The concentrations of lead in the blood of the calves exposed in utero were low (0.010-0.095 ppm).     

Suspected monensin toxicosis in feedlot cattle

Suspected monensin toxicosis was seen in feedlot cattle aged 6 to 9 months. Twenty cattle died following inclusion of monensin in the feed at 400g/tonne, which was 13 times the recommended level. The deaths occurred over 2 weeks. Clinical signs were inappetance, respiratory distress and sudden death. Post-mortem features were those of right-sided heart failure and included dependent subcutaneous oedema, ascites, hydrothorax, and periancinar hepatocyte congestion and necrosis. However, in contrast to previous reports no myocardial necrosis was found, but focal skeletal muscle necrosis was observed. Additional findings were marked pulmonary oedema accompanied by fibrin and erythrocyte exudation into alveoli and interlobular lymphatics. From these findings it appears that monensin, as well as affecting both cardiac and skeletal muscle, has a primary effect on lung vasculature.     

Accidental monensin sodium intoxication of feedlot cattle

Of 1,994 yearling and 2-year-old cattle in a winter feeding program, 117 died within 42 days of being fed toxic amounts of monensin sodium in a liquid protein supplement. Death losses commenced on the third day after ingestion of a toxic amount in the feed. Clinical signs in cattle that died in less than 9 days included anorexia, pica, diarrhea, depression, mild hindlimb ataxia, and dyspnea. Gross necropsy findings in cattle dying in the acute phase of the illness included hydrothorax, ascites, and pulmonary edema, as well as petechial hemorrhages, edema, and yellow streaking in skeletal and cardiac muscle. Cattle dying after 9 days had gray streaks in heart and skeletal muscle, generalized ventral edema, enlarged, firm, bluish discolored liver, and enlarged heart. Microscopic changes in cattle dying in the acute phase (less than 9 days) consisted of pulmonary edema, congestion, and hemorrhage. Cardiac and skeletal muscle had localized areas of edema, hemorrhage, and coagulative necrosis. In cattle dying after 9 days of illness, the changes included lymphocytic infiltration, sarcolemmal nuclear proliferation, and fibrosis in skeletal and cardiac muscle. Lungs contained increased alveolar macrophages and a few neutrophils. Centrilobular necrosis and mild fibrosis were found in the liver. Changes varied somewhat according to the area of heart or skeletal muscle that was affected. Active muscles, eg, those in the heart ventricles and diaphragm, were altered most severely. Intoxication appeared to be a result of sedimentation of monensin in the molasses carrier to give remarkable concentrations of the substance at the bottom of the holding tank.     

Interaction of T-2 fusariotoxin and monensin in broiler chickens infected with Coccidia

Field observations suggest that coccidiosis is a common cause of death in broiler chicken flocks fed diets containing sufficient amounts of ionophore antibiotics (monensin, narasin, etc.) and contaminated with mycotoxins, particularly with T-2 fusariotoxin. To study this phenomenon, broiler chickens fed diets containing different amounts of T-2 toxin and free from monensin, or containing a preventive dose (100 mg/kg of feed) of monensin, were infected experimentally with coccidian oocysts. In all groups fed a diet containing monensin plus T-2 toxin severe clinical symptoms of coccidiosis (blood-stained faeces etc). occurred. Deaths and retarded growth depended on the toxin dose and were considerable. The body mass gain of chicks fed a diet containing monensin and T-2 toxin but not infected with coccidia was inferior to that of groups fed diets which contained either monensin or T-2 toxin (experiment 2). On the basis of these findings a negative interaction of the two compounds is assumed. This seems to be supported by the results of experiment 3, i. e. the finding that the lethal dose of narasin, a compound closely related to monensin both in chemical structure and mechanism of action, proved to be much lower (LD50 = 102 mg/kg body mass) for chickens fed a diet supplemented with T-2 toxin than for the control chickens (LD50 = 176 mg/kg body mass). The present results suggest that the feeding of diets severely contaminated with T-2 toxin may alter the anticoccidial efficacy of monensin.     

Plant-animal interactions in larkspur poisoning in cattle

Larkspur (Delphinium spp.) toxicity in cattle seriously impedes the efficient use of productive mountain rangelands. Larkspurs contain complex diterpenoid alkaloids that cause acute intoxication and death from respiratory paralysis. Alkaloids and their concentrations vary among larkspur species, plant parts and phenological growth stages, thus causing great variability in toxicity. Ingestion rate of larkspur by the cow, alkaloid toxicity and concentration in the plant and the kinetics of absorption and excretion interact to determine whether a cow is poisoned. Plant and animal factors influencing consumption and subsequent intoxication must be further elucidated to devise management strategies to reduce liverstock losses.     

Diquat poisoning of dairy cattle by topical application

This case report describes poisoning of dairy cattle from a dermal challenge of 50 to 100 mg/kg body weight diquat. Five of 36 cattle exposed, demonstrated clinical signs of intoxication, dehydration, and death over 5 days. Diquat poisoning of cattle by the dermal route has not previously been reported.     

Basis for regulation of selenium supplements in animal diets.

Selenium was discovered 174 yr ago but, until 1957, was given little notice by biologists or was vilified as an agent that caused toxicity in grazing ruminants and horses in the northern Great Plains. After its status as an essential nutrient was established, Se received intense scrutiny, and hundreds of papers have been published dealing with its metabolic functions and the consequences of a Se deficiency. Because regions of Se deficiency are so extensive in the United States, great efforts have been made to gain Food and Drug Administration (FDA) approval for Se supplementation of animal diets. Initially, these efforts were thwarted by concern that Se might be carcinogenic. After this concern was resolved, researchers established supplemental Se levels that were efficacious, safe for animals, safe for humans that eat animal products, and protective of the environment. First approval of Se supplements was given in 1974 for supplementation of swine or growing chicken diets at .1 ppm. Supplements for turkey diets were approved at .2 ppm. Ultimately, in 1987, levels of supplemental Se in diets for chickens, turkeys, ducks, swine, sheep, and cattle were approved at .3 ppm. However, FDA regulations do not mention horses or zoo animals, and those who would ensure the welfare of these species by supplementing Se-deficient diets may be in violation of FDA interpretation of the law. In addition, the association of Se with death and deformities in aquatic birds at the Kesterson Reservoir in California has led to pressure on the FDA to reverse the 1987 amendments to the feed additive regulation.(ABSTRACT TRUNCATED AT 250 WORDS)