Monensin

692.85

670.87

244-941-7

343257

DTXSID4048561

Crystals

153

log Kow = 5.43 (est)

1.0773 (rough estimate)

103-105 °C

608.24°C (rough estimate)

1.5465 (estimate)

In water, 3.0X10-3 mg/L at 25 °C (est)

2-8°C

5.2X10-23 mm Hg at 25 °C (est)

LD50 of monensin complex in mice, chicks (mg/kg): 43.8 ± 5.2, 284 ± 47 orally (Haney, Hoehn)

D +47.7°

pKa = 6.6 (in 66% N,N-dimethylformamide)|pKa = 4.2 (est)

Very stable under alkaline conditions.|Off-white to tan, crystalline powder. MP: 267-269 °C. Specific optical rotation: +47.3 deg at 25 °C/D (methanol). Soluble in chloroform, methanol and other organic solvents; slightly soluble in water. Practically insolluble in solvent hexane. /Monensin sodium salt/

II

6.1(a)

UN 3462 6.1/PG 2

3

25

36/37/39-45

JH2830000

T

Stable under recommended storage conditions. /Monensin sodium salt/

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product. /Monensin sodium salt/

Incompatible materials: Strong oxidizing agents. /Monensin sodium salt/

The tolerances for residues of monensin are: (1) Cattle-(i) Liver. 0.10 part per million (ppm). (ii) Muscle, kidney, and fat. 0.05 ppm. (iii) Milk. Not required. (2) Goats-(i) Edible tissues. 0.05 ppm. (3) Chickens, turkeys, and quail. A tolerance for residues of monensin in chickens, turkeys, and quail is not required.|Monensin. New animal drug for use in animal feeds. Conditions of use in broiler chickens, turkeys, cattle, replacement chickens intended for use as cage layers, bobwhite quail, and goats.|The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Monensin is included on this list.|The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Monensin sodium is included on this list. /Monensin sodium/

|Danger|H300: Fatal if swallowed [Danger Acute toxicity, oral]|P264, P270, P301+P310, P321, P330, P405, and P501|H301: Toxic if swallowed [Danger Acute toxicity, oral]|P260, P264, P270, P280, P301+P310, P305+P351+P338, P309+P311, P321, P330, P332+P313, P337+P313, P405, and P501|P260, P261, P264, P270, P272, P280, P301+P310, P302+P352, P307+P311, P314, P321, P330, P333+P313, P363, P405, and P501

Skin protection: Handle with gloves. /Monensin sodium salt/|Eye/face protection Face shield and safety glasses: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). /Monensin sodium salt/|Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). /Monensin sodium salt/|Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. /Monensin sodium salt/

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary. /Monensin sodium salt/|Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. /Monensin sodium salt/

Accidental Release Measures. Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. /Monensin sodium salt/

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.|Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product. /Monensin sodium salt/|Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. /Monensin sodium salt/|Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. /Monensin sodium salt/

An eye & skin irritant.

Monensin concentrations in leachate from a livestock mortality pit reached a maximum of 11,980 ng/L at about 200 days post burial, this calculates to an estimated mass loading of 1.01 ug/kg of buried cattle carcass material(1). Monensin was detected in rainfall runoff from poultry litter fertilized soil(2).

SEDIMENT: Monensin was detected in sediment samples collected March and September of 2011 from the Bay of Cadiz, Spain; samples were from 6 locations (Chiclana de la Frontera, Puerto Real, Cadiz, two locations at El Puerto di Santa Maria and Rota); concentrations were 0.10 mg/kg or less except Rota which was <0.10-3.00 mg/kg(1).|SOIL: Monensin was detected in Canada soil at 0.8-1.08 mg/kg(1). Monensin was detected in poultry litter fertilized soil an a concentration of 183 ug/kg(2).

Monensin was detected in cattle feces/manure in samples collected in Canada at 0.7-4.7 ng/L(1). Monensin was detected in poultry litter at a maximum concentration of 4 mg/kg(2).

IDENTIFICATION AND USE: Monensin is a polyether carboxylic ionophore antibiotic. Monensin is a mixture of four analogues, A, B, C and D, with monensin A being the major component (98%). Depending on the method of purification, monensin can exist in mycelial, crystalline and recrystallized forms. It is used for the treatment of coccidiosis in poultry (chickens, turkeys and quail) and ruminants (cattle, sheep and goats). Monensin is also used to control ketosis and bloat in cattle and as a growth promoter feed additive in cattle and sheep. Monensin is mainly effective against Gram-positive bacteria. HUMAN EXPOSURE AND TOXICITY: 17 year-old boy who developed myoglobinuria, renal failure and death 11 days after ingesting sodium monensin. In another case, a patient took a dose of monensin three times higher than a dose considered lethal for cattle and developed a clinical picture similar to that reported in veterinary medicine. There was an early and extremely severe rhabdomyolysis followed by acute renal failure, heart failure, and death. The main changes observed at autopsy were extensive skeletal muscle necrosis, complement deposition at the myocardial level, pulmonary edema, & acute tubular damage. ANIMAL STUDIES: Acute toxicity was examined in mature rhesus monkeys. Pairs of monkeys were exposed to a single dose of 20, 40 or 60 mg monensin/kg bw by gavage and were monitored for 7 days. All animals survived and developed diarrhea within 24 hr after dosing. Adult goats were administered sodium monensin, 13.5 mg kg (-1), daily for five consecutive days via gastric gavage. Monensin exposure caused diarrhea, tachycardia and reduction in ruminal movements and body temperature. In an inhalational exposure study, rats were exposed to either normal air or air containing particulate mycelial monensin sodium at a mean concentration of 79 mg/cu m for 2 weeks (1 hr/day, 5 days/week). Nine of 10 treated females became anorexic and lost weight during the 2nd week of the study. Slight focal myositis of the skeletal muscle was seen in two males and two females but none of the controls. Multifocal myocardial changes were observed in male rats treated with monensin. In a subchronic study, male and female mice were fed diets containing 0, 37.5, 75, 150 or 300 mg mycelial monensin sodium/kg for 3 months. A dose-dependent decrease in body weight gain occurred in all dose groups. At the end of the study, the decrease ranged from 27% and 21% in the lowest dose group in females and males, respectively, to 99% in the highest dose group in both sexes. In a chronic toxicity study, male and female rats were maintained on a diet containing 25, 56 or 125 mg crystalline monensin sodium/kg, whereas control rats received a normal diet for 2 years. Body weight and weight gain were significantly decreased in animals receiving 125 mg monensin/kg in their diet and were transiently decreased during the first 4 months in rats in the middle dose group. Benign and malignant neoplasms were observed in treated and untreated animals, with no association between monensin administration and neoplasm type or severity. Monensin is toxic in horses. Clinical signs were tachycardia and cardiac arrythmia, groaning, incoordination, sudoresis, recumbency, and paddling movements with the limbs before death. Main necropsy findings were in the skeletal muscles and myocardium. The effects of exposure to monensin during development were studied in rats. Groups of female rats received monensin at concentrations of 0, 100 or 300 mg/kg until premating weights achieved 185 g and during pregnancy and lactation. Female body weight was significantly decreased in the highest dose group after 8 days of treatment. The body weights of male and female pups in the highest dose group were reduced from postnatal day 10 until postnatal day 21. Male offspring in the low dose group showed body weight reduction only on postnatal day 21. No external signs of malformation were detected in the pups. A study was also undertaken to explore the effects of monensin, a potent Golgi disturbing agent on male fertility. Male rats were administered monensin at the dose levels of 2.5, 5, and 10 mg/kg b wt. Animals were sacrificed after 67 days of the treatment. The findings from electron microscopy such as membrane disruption, swelling and disintegration of Golgi apparatus strongly suggest the interference of monensin with the functioning of Golgi apparatus in the spermatogenic cells. Data from the sperm number and motility as well as the fertility studies and the resulted litter size further points towards the antifertility effects of monensin in male rats. Genotoxicity tests were negative.

An experiment was carried out with male broiler chicks to evaluate the combined effect of monensin (150 mg/kg) & the growth promoters (GPs) Zn bacitracin (BAC, 50 mg/kg), virginiamycin (VIR, 25 mg/kg) & avoparcin (AVO, 20 mg/kg) fed from 7 to 28 days of age on performance, utilization of dietary nutrients, yield of defeathered eviscerated carcases (DEC) & size of various organs. The effect of the GPs in the monensin-unsupplemented diets fed up to 49 d of age on performance & carcase was also determined. Monensin significantly (P < 0.05) depressed food intake, weight gain & food efficiency from 7 to 28 d of age. None of the GPs was able to counteract these effects. However, AVO slightly ameliorated them. AVO also significantly increased food intake & improved gain & food efficiency during 7 to 28, but not 28 to 49 or 7 to 49 d of age. VIR & BAC did not affect performance in either age period. Monensin did not affect the utilisation of dietary dry matter, fat or energy, but it significantly decreased nitrogen utilisation. AVO improved nitrogen & fat utilisation & increased dietary AME(n) content. AME(n) was also increased by VIR. The utilisation of these nutrients was not affected by the interactions between monensin & the GPs. Monensin did not affect yield of the DEC or the relative liver size at 31 d of age. It significantly increased the relative length of the small intestine (SI) & decreased its specific weight. AVO significantly increased yield at 31, but not at 53 d of age. BAC & VIR did not affect this variable. AVO & VIR, but not BAC, at both age periods reduced, at times significantly, the size, length & specific weight of the SI. Our conclusions: BAC, VIR & AVO do not counteract the toxic effect of monensin. The effect of GPs in improving performance decreases & even disappears with age, while their effect in reducing the size of the SI is still evident in 49 day old birds.|In this study, co-admin of the ionophore monensin was not shown to alter blood levels of enrofloxacin or norfloxacin.|The characteristics of the toxic interaction between monensin & tiamulin were investigated in rats. A three-day comparative oral repeated-dose toxicity study was performed in Phase I, when the effects of monensin & tiamulin were studied separately (monensin 10, 30, & 50 mg/kg or tiamulin 40, 120, & 200 mg/kg body weight, respectively). In Phase II, the two compounds were administered simultaneously to study the toxic interaction (monensin 10 mg/kg & tiamulin 40 mg/kg bw, respectively). Monensin proved to be toxic to rats at doses of 30 & 50 mg/kg. Tiamulin was well tolerated up to the dose of 200 mg/kg. After combined administration, signs of toxicity were seen (including lethality in females). Monensin caused a dose-dependent cardiotoxic effect & vacuolar degeneration of the skeletal muscles in the animals given 50 mg/kg. Both compounds exerted a toxic effect on the liver in high doses. After simultaneous administration of the two compounds, there was a mild effect on the liver (females only), hydropic degeneration of the myocardium & vacuolar degeneration of the skeletal muscles. The alteration seen in the skeletal muscles was more marked than that seen after the administration of 50 mg/kg monensin alone.|Cultured rat hepatocytes were treated with potassium cyanide, an inhibitor of cytochrome oxidase; valinomycin, a K+ ionophore; carbonyl cyanide m-chlorophenylhydrazone (CCCP), a protonophore; and the ATP synthetase inhibitor oligomycin. The effect of these agents on the viability of the cells was related to changes in ATP content and the deenergization of the mitochondria. The ATP content was reduced by over 90% by each inhibitor. All of the agents except oligomycin killed the cells within 4 h. With the exception of oligomycin, the mitochondrial membrane potential as measured by the distribution of [3H]triphenylmethylphosphonium collapsed with each of the agents. Monensin, a H+/Na+ ionophore, potentiated the toxicity of cyanide and CCCP, whereas the toxicity of valinomycin was reduced. The effect of cyanide and monesin on the cytoplasmic pH of cultured hepatocytes was measured with the fluorescent probe, 2',7'-biscarboxyethyl-5,6-carboxyfluorescein. Cyanide promptly acidified the cytosol, and the addition of 10 microM monensin caused a rapid alkalinization of the cytosol. A reduction of pH of the culture medium from 7.4 to 6.6 and 6.0 prevented the cell killing both by cyanide alone and by cyanide in the presence of monensin. However, neither monensin nor extracellular acidosis had any effect on the loss of mitochondrial energization in the presence of cyanide. It is concluded that ATP depletion per se is insufficient to explain the cell killing with cyanide, CCCP, and valinomycin. Rather, cell killing is better correlated with a loss of mitochondrial energization. With cyanide an intracellular acidosis interferes with the mechanism that couples collapse of the mitochondrial membrane potential to lethal cell injury.|For more Interactions (Complete) data for MONENSIN (9 total), please visit the HSDB record page.

LD50 Rat oral 100 mg/kg|LD50 Rat ip 15 mg/kg|LD50 Mouse oral 43,800 ug/kg|LD50 Mouse ip 10 mg/kg|LD50 Horse oral 2 mg/kg

/OTHER TERRESTRIAL SPECIES/ A field experiment was initiated whereby a series of replicated plots received annual applications of ivermectin, monensin, and zinc bacitracin, either singly or in a mixture. Pharmaceuticals were added at concentrations of 0.1 mg/kg soil or 10 mg/kg soil. The authors collected soil samples in 2013, before and after the fourth annual application of pharmaceuticals. In addition, a 30-day laboratory experiment was undertaken with the same soil and same pharmaceuticals, but at concentrations of 100 mg/kg soil. The impact of the pharmaceuticals on nitrification rates, on the abundance of ammonia-oxidizing bacteria (AOB), and on the abundance of ammonia-oxidizing archaea (AOA) was assessed. None of the pharmaceuticals at 0.1 mg/kg had any effect on nitrification. Referenced to control soil, nitrification was accelerated in soil exposed to 100 mg/kg zinc bacitracin or 10 mg/kg of the pharmaceutical mixture, but none of the treatments inhibited nitrification. Neither AOB abundance nor AOA abundance was affected by the pharmaceuticals at 0.1 mg/kg. At 10 mg/kg, monensin, zinc bacitracin, and a mixture of all 3 pharmaceuticals suppressed the abundance of AOB, and zinc bacitracin and the mixture increased AOA abundance. The decrease in AOB abundance and increase in AOA abundance when exposed to 10 mg/kg soil suggests that AOB are more sensitive to these chemicals and that AOA populations can expand to occupy the partially vacated niche.

Monensin is a major component of the antibiotic complex isolated from Streptomyces cinnamonensis(1).

Monensin's production and use as a growth enhancement agent in cattle and an anticoccidial drug in poultry(1), may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values of 125-5700(2), indicate that monensin is expected to have moderate to no mobility in soil(SRC). The pKa of monensin is estimated as 4.2(3), indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of monensin from moist soil surfaces is not expected to be an important fate process given the estimated pKa(3). Monensin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.2X10-23 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Monensin was degraded 40-75% in soil in 7 day aerobic studies, approximately 20% was attributed to abiotic reactions and the remaining portion was considered biodegradation(6). Other degradation studies indicated half-lives of of 3.8 and 3.3 days in unamended and manure amended soil, respectively(7).|Monensin degraded to trace levels in 20 days in manure amended and unamended field soil plots treated at an initial concentration of 1 ppm; no monensin was detectable after 33 days(1). Monensin was reported as being persistent under anaerobic conditions, with 30-40% biodegradation expected in 10 weeks, but more degradation occurred under aerobic conditions(2). Monensin, applied to agricultural soil May 29, 2004 in Northumberland County, Ontario, Canada at a rate of 1 mg/kg, had degradation half-lives of 3.8 and 3.3 days in unamended soil (organic matter 3.2-3.5%, pH 5.4-5.5) and manure amended soil (organic matter 3.6-4.1%, pH 5.7-5.8), respectively(3).|AQUATIC FATE: Based on a classification scheme(1), Koc values of 125-5700(2), indicate that monensin may be adsorb to suspended solids and sediment(SRC). An estimated pKa of 4.2(3) indicates monensin will exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). Monensin was stable to hydrolysis at pH 7 and 9, but had a hydrolysis half-life of 13 days at pH 4 and 25 °C(4). According to a classification scheme(5), an estimated BCF of 10(SRC), from an estimated log Kow of 5.43(6) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available, however soil degradation studies, monensin degraded 40-75% in 7 days, approximately 20% was attributed to abiotic reactions and the remaining portion was considered biodegradation(7).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), monensin, which has an estimated vapor pressure of 5.2X10-23 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase monensin may be removed from the air by wet and dry deposition(SRC). Monensin did not absorb light at environmentally relevant wavelengths(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

Monensin was stable to hydrolysis at pH 7 and 9, but had a hydrolysis half-life of 13 days at pH 4 and 25 °C(1). Hydrolysis half-lives in another study were 1.7 and 6.7 days at pH 3 and 4, respectively, with no hydrolysis at pH values of 7 or above(2). Monensin did not absorb light at environmentally relevant wavelengths(1) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC). Monensin did not undergo aquatic photodegradation(3).

An estimated BCF of 10 was calculated in fish for monensin(SRC), using an estimated log Kow of 5.43(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Measured Koc values for monensin were 125-5700(1). According to a classification scheme(2), this Koc range suggests that monensin is expected to have moderate to no mobility in soil. The estimated pKa of monensin is 4.2(3), indicating that this compound will exist almost entirely in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).|The Koc for monensin was determined in various soils collected from the US and Korea(1).[Table#6654]

An estimated pKa of 4.2(1) indicates monensin will exist almost entirely in anion form at pH values of 5 to 9 and, therefore, volatilization from water and moist soil surfaces is not expected to be an important fate process(SRC). Monensin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.2X10-23 mm Hg(SRC), determined from a fragment constant method(2).

SURFACE WATER: Monensin was detected in 80% of 213 surface water samples collected from 1994 to 2000 from US streams in the Great Lakes basin(1). Monensin was detected at 0.30-3.41 ug/L in 3 of 26 surface water samples collected throughout the Bosque River Watershed, Texas(2). Monensin was detected in one of 634 surface water samples collected from 1996 to 2005 in the Netherlands(3).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 4516 workers were potentially exposed to monensin in the US(1). Occupational exposure to monensin may occur through inhalation and dermal contact with this compound at workplaces where monensin is produced or used(SRC). Monitoring data indicate that the general population may be exposed to monensin via dermal contact with contaminated soil or water(SRC).

Antifungal Agents; Antiprotozoal Agents; Coccidiostats|/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Monensin is included in the database.|MEDICATION (VET): Chickens: As an aid in the prevention of coccidiosis caused by Eimeria necatrix, E. tenella, E. acervulina, E. brunetti, E. mivati, and E. maxima. /Included in US product label/|MEDICATION (VET): Turkeys: For the prevention of coccidiosis in turkeys caused by Eimeria adenoeides, E. meleagrimitis and E. gallopavonis. /Included in US product label/|For more Therapeutic Uses (Complete) data for MONENSIN (12 total), please visit the HSDB record page.

/BOXED WARNING/ Warning: Do not feed to laying chickens. Do not feed to chickens over 16 weeks of age. When mixing and handling Coban 90, use protective clothing, impervious gloves, and a dust mask. Operators should wash thoroughly with soap and water after handling. If accidental eye contact occurs, immediately rinse thoroughly with water.|/BOXED WARNING/ Caution: For replacement chickens intended for use as cage layers only. Do not allow horses, other equines, mature turkeys, or guinea fowl access to feed containing monensin. Ingestion of monensin by horses and guinea fowl has been fatal. Some strains of turkey coccidia may be monensin tolerant or resistant. Monensin may interfere with development of immunity to turkey coccidiosis. In the absence of coccidiosis in broiler chickens the use of monensin with no withdrawal period may limit feed intake resulting in reduced weight gain.

Chemical agents that increase the permeability of CELL MEMBRANES to SODIUM ions. (See all compounds classified as Sodium Ionophores.)|Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. (See all compounds classified as Antifungal Agents.)|Substances that are destructive to protozoans. (See all compounds classified as Antiprotozoal Agents.)|Agents useful in the treatment or prevention of COCCIDIOSIS in man or animals. (See all compounds classified as Coccidiostats.)|Chemical agents that increase the permeability of CELL MEMBRANES to PROTONS. (See all compounds classified as Proton Ionophores.)

The pharmacokinetics of monensin, including half-life, apparent volume of distribution, total body clearance, systemic bioavailability and tissue residues were determined in broiler chickens. The drug was given by intracrop and intravenous routes in a single dose of 40 mg/kg body weight. Following intravenous injection the kinetic disposition of monensin followed a two compartments open model with absorption half life of 0.59 hr, volume of distribution of 4.11 l/kg and total body clearance of 28.36 ml/kg/min. The highest serum concentrations of monensin were reached 0.5 hr after intracrop dosage with an absorption half-life of 0.27 hr and an elimination half life of 2.11 hr. The systemic bioavailability was 65.1% after intracrop administration. Serum protein-binding tendency of monensin calculated in vitro was 22.8%. Monensin concentrations in the serum and tissues of chickens after a single intracrop dose of pure monensin (40 mg/kg body weight) were higher than those after feeding a supplemented monensin premix (120 mg/kg) for 2 weeks. Monensin residues were detected in tested body tissues, collected 2, 4, 6 and 8 hr after oral administration. The highest concentration was found in the liver. In addition, monensin residues were detected only in liver, kidney and fat 24 hr after the last oral dose. No monensin residues could be detected in tissues after 48 hr, except in liver which cleared completely by 72 hr.|Six chickens were exposed to (3)H-monensin sodium at 121 mg/kg in the diet for 2 days. Only 52-73% of the radioactivity was recovered; of this, 97% was found in the faeces. The reason for poor radioactivity balance was unknown. /Monensin sodium/|Broiler chickens were administered (14)C-monensin sodium at a concentration of 120 mg/kg in the diet for 4 days (two males, three females) or 6 days (three males, three females). Six hours after withdrawal from the treated feed, radioactivity was detected in the liver, kidney, fat and skin, with the highest level detected in the liver (0.5 mg/kg liver). No radioactivity was detected in the muscle tissue. /Monensin sodium/|Ten White Leghorn roosters and two White Leghorn hens were exposed orally to a single dose of (14)C-monensin in a gelatine capsule (dose range: 2.6-100 mg). Some birds were colostomized, whereas others had bile cannulae inserted. Absorption in the chickens ranged from 11% to 31% of the ingested (14)C-monensin. The primary route of excretion was in the faeces, with a small proportion excreted in the urine and by respiration.|For more Absorption, Distribution and Excretion (Complete) data for MONENSIN (21 total), please visit the HSDB record page.

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. ...|The O-demethylation of monensin is greater in microsomes from phenobarbital-treated rats than in untreated rats and is dependent on reduced nicotinamide adenine dinucleotide phosphate (NADPH), suggesting that monensin is a cytochrome P450 (CYP) enzyme substrate. The oxidative metabolism of monensin appears to occur at least in part by CYP3A, since treatment of rat hepatic microsomes with chemical inducers of CYP3A significantly increased monensin O-demethylation. It has been speculated that competition between monensin and other CYP3A substrates may explain accidental poisonings that have occurred in several domestic species following coadministration of monensin and other chemotherapeutic agents, since monensin metabolism is significantly decreased in the presence of other CYP3A substrates in rats.|Monensin metabolites result mainly from O-demethylation at the methoxylic group and/or hydroxylation at several places on the ionophore backbone. ... Although it is difficult to obtain sufficient monensin metabolites to test activity, four metabolites generated by rat liver microsomes, including a by-product of monensin production (O-desmethylmonensin), have been tested and have at least 10- to 20-fold less antibacterial, anticoccidial, cytotoxic, cardiotonic and ionophoric activity than the parent compound, indicating that metabolism eliminates most of the biological activity of monensin.|Monensin is extensively metabolized in the liver, producing more than 50 different metabolites that have been detected in the liver, bile and faeces of chickens, cattle, rats, pigs, dogs, turkeys, sheep and horses. In most species (chickens, rats, dogs, turkeys and pigs), less than 10% of monensin is excreted as the parent compound, whereas a study in calves indicated that 50-68% of the (14)C identified in the feces was unmetabolized monensin. This difference in amount of metabolized monensin may have been a result of differences in absorption of the molecule in different species. Total microsomal monensin metabolism, estimated by measuring the rate of substrate disappearance by a high-performance liquid chromatographic (HPLC) analytical method, is highest in cattle, intermediate in rats, chickens and pigs, and lowest in horses. The pattern of metabolites is qualitatively similar between laboratory and non-laboratory animal species, although quantitative differences exist. No single metabolite dominates the metabolic profile.|The metabolism of monensin sodium in human liver microsomes has been compared with metabolism in the microsomes of horses and dogs. A pooled human microsomal sample from multiple donors (male and female, Caucasian, Hispanic and African American, 15-66 years old), pooled dog microsome sample and equine microsomes from a single donor were incubated with 0.5, 1 and 10 ug monensin/mL in the presence or absence of NADPH. The metabolite profiles were examined at 0, 5, 10, 20, 40 and 60 min by liquid chromatography/mass spectrometry (LC-MS) analysis. Monensin was metabolized by first-order kinetics in all species, and metabolism was extensive (93-99% by 60 min). The turnover of monensin in humans was similar to that in dogs, whereas the turnover in horses was only 10% of that in dogs and humans.

The pharmacokinetics of monensin, including half-life, apparent volume of distribution, total body clearance, systemic bioavailability and tissue residues were determined in broiler chickens. The drug was given by intracrop and intravenous routes in a single dose of 40 mg/kg body weight. Following intravenous injection the kinetic disposition of monensin followed a two compartments open model with absorption half life of 0.59 hr ... .The highest serum concentrations of monensin were reached 0.5 hr after intracrop dosage with an absorption half-life of 0.27 hr and an elimination half life of 2.11 hr. ...

The Wnt signaling pathway is required during embryonic development and for the maintenance of homeostasis in adult tissues. However, aberrant activation of the pathway is implicated in a number of human disorders, including cancer of the gastrointestinal tract, breast, liver, melanoma, and hematologic malignancies. In this study, we identified monensin, a polyether ionophore antibiotic, as a potent inhibitor of Wnt signaling. The inhibitory effect of monensin on the Wnt/beta-catenin signaling cascade was observed in mammalian cells stimulated with Wnt ligands, glycogen synthase kinase-3 inhibitors, and in cells transfected with beta-catenin expression constructs. Furthermore, monensin suppressed the Wnt-dependent tail fin regeneration in zebrafish and Wnt- or beta-catenin-induced formation of secondary body axis in Xenopus embryos. In Wnt3a-activated HEK293 cells, monensin blocked the phoshorylation of Wnt coreceptor low-density lipoprotein receptor related protein 6 and promoted its degradation. In human colorectal carcinoma cells displaying deregulated Wnt signaling, monensin reduced the intracellular levels of beta-catenin. The reduction attenuated the expression of Wnt signaling target genes such as cyclin D1 and SP5 and decreased the cell proliferation rate. In multiple intestinal neoplasia (Min) mice, daily administration of monensin suppressed progression of the intestinal tumors without any sign of toxicity on normal mucosa. Our data suggest monensin as a prospective anticancer drug for therapy of neoplasia with deregulated Wnt signaling.|Preincubation of rat soleus muscle with 1 & 10 uM monensin for 2 hr increased the subsequent basal 2-deoxyglucose uptake by muscle 76 & 121% respectively. Under the same conditions, monensin decreased the insulin-stimulated (1 mU/mL) 2-deoxyglucose uptake by 29 & 37% respectively. The monensin-induced augmentation of basal 2-deoxyglucose uptake was inhibited 92% by cytochalasin B suggesting that the uptake is mediated by glucose transporters. Monensin did not incr the cellular accumulation of L-glucose in muscle indicating that it does not affect the cell membrane integrity. Neither the stimulatory effect of monensin on basal 2-deoxyglucose uptake nor the opposite, inhibitory action of monensin on the insulin-stimulated 2-deoxyglucose uptake were influenced by the removal of Ca2+ from the medium or by dantrolene, an inhibitor of Ca2+ release from the sarcoplasmic reticulum, suggesting that the actions of monensin are not mediated by calcium. Monensin had no effect on muscle ATP concn. The monensin-induced augmentation of basal 2-deoxyglucose uptake was neither associated with stimulation of muscle phosphatidylinositol 3-kinase activity nor inhibited by wortmannin, demonstrating that the incr in basal 2-deoxyglucose uptake is not mediated by activation of phosphatidylinositol 3-kinase. The inhibition of insulin-stimulated 2-deoxyglucose uptake by monensin was associated with a 31% decr in the abundance of insulin receptors in muscles, a 64% decr in the insulin-induced autophosphorylation of the insulin receptor beta-subunit, & a 44% reduction of the insulin-stimulated phosphatidylinositol 3-kinase activity. Addition of monensin into the phosphatidylinositol 3-kinase reaction had no effect on the activity of the enzyme, demonstrating that the inhibition in monensin-treated muscles is indirect & occurs upstream of phosphatidylinositol 3-kinase. It is concluded that monensin has a dual effect on 2-deoxyglucose uptake by skeletal muscle: it stimulates basal uptake but inhibits the insulin-stimulated uptake. The primary cause of the latter, inhibitory effect of monensin is at the level of the insulin receptor.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/|Emergency and supportive measures. 1. Maintain an open airway and assist ventilation if necessary. 2. Treat coma, seizures, hypotension, anaphylaxis, and hemolysis if they occur. 3. replace fluid losses resulting from gastroenteritis with IV crystalloids. 4. Maintain steady urine flow with fluids to alleviate crystalluria from overdoses of sulfonamides, ampicillin, or amoxicillin. /Antibacterial agents/|For more Antidote and Emergency Treatment (Complete) data for MONENSIN (6 total), please visit the HSDB record page.

/CASE REPORTS/ ... The patient took a dose of monensin three times higher than a dose considered lethal for cattle & developed a clinical picture similar to that reported in veterinary medicine. There was an early & extremely severe rhabdomyolysis followed by acute renal failure, heart failure, & death. The main changes observed at autopsy were extensive skeletal muscle necrosis, complement deposition at the myocardial level, pulmonary edema, & acute tubular damage.|/CASE REPORTS/ ... A case of a 17 year-old boy who developed myoglobinuria, renal failure & death 11 days after ingesting sodium monensin, possibly with the intention of developing muscles /was reported/. /Sodium monensin/

Coban

Oral (Feed): Coban 90 Monesin Granules, Active Drug Ingredient - Monensin, USP - 90.7 g per pound.|Oral (Feed): Rumensin 90 Monensin Granule, Active drug ingredients: Monensin granulated, USP, 90.7 g monensin activity per pound.

Monensin is generally used as the sodium salt. Monensin is a mixture of four analogues, A, B, C and D, which are produced during fermentation, with monensin A being the major component (98%). ... Depending on the method of purification, monensin can exist in mycelial, crystalline and recrystallized forms.|... was found in the mycelium of Streptomyces cinnamonensis by Eil Lilly and Co in 1967 in the course of screening for anticoccidial and growth-promoting substances for cattle, swine, and chickens.

A method using liquid chromatography tandem mass spectrometry (LC-MS-MS) with electrospray (ES) for the determination of traces of narasin, monensin & salinomycin in chicken liver & eggs was developed, validated & used for routine surveillance. The essence of this paper is to demonstrate that one single method can serve very well for two entirely different purposes, i.e., screening & confirmation. Highly reliable confirmation of the identity at low concentrations was demonstrated when residues of narasin were detected & quantified (0.2 to 11 ng g(-1)) in 50% of the Swedish eggs analysed in 1999. Four daughter ions were detected with ion ratios meeting suggested confirmation criteria for the European Union, even at 0.2 ng g(-1). The method was found to be highly cost-effective since both screening & confirmation of 98 liver samples were performed in only two analytical runs (the Swedish national surveillance scheme of 1999, report level 5 ng g(-1)). The high performance of the method for the different applications was possible due to a combination of the power of ES-LC-MS-MS, a procedure involving screening of pooled samples, & method optimisation of the work-up (automated solid phase extraction), LC & MS parameters. Validation data for narasin (0.5 to 20 ng g(-1)) in eggs are presented (accuracy 94 to 108%, relative standard deviation 4 to 10%, limit of detection 0.026 ng g(-1)). The time for an LC-MS-MS run was 4 min, corresponding to 48 s per sample in a pool.