A multi-approach analysis of the toxicity of a commercial formulation of monensin on Rhinella arenarum embryos and larvae.

Monensin, an antibacterial commonly used in animal fattening, can enter aquatic ecosystems and harm non-target organisms. Since there are no previous studies about the effects of monensin on amphibians, the aim of the present study was to evaluate the lethal and sublethal toxicity of a commercial formulation of monensin (CFM) through standardized bioassays with embryos and larvae of the amphibian Rhinella arenarum. Oxidative stress (catalase and glutathione S-transferase activities, and reduced glutathione and lipid peroxidation levels), cholinesterasic effect (acetylcholinesterase and butyrylcholinesterase activities) and mutagenicity (micronuclei frequency) biomarkers were evaluated. The CFM produced teratogenic effects, with a teratogenic index of 6.21. Embryos (504 h-LC50: 273.33 µg/L) were more sensitive than larvae, as no significant mortality was observed on larvae exposed up to 3000 µg/L for 504 h. However, oxidative stress, cholinesterasic effect and mutagenicity biomarkers were altered on larvae exposed for 96 h to environmentally relevant concentrations (4, 12 and 20 µg/L of monensin active ingredient). The CFM caused adverse effects on the exposed organisms, primarily on embryos, leading to lethal and sublethal effects, which could impact the wildlife when it reaches aquatic ecosystems.

Effect of the veterinary ionophore monensin on the structure and activity of a tropical soil bacterial community.

Monensin (MON) is a coccidiostat used as a growth promoter that can reach the environment through fertilization with manure from farm animals. To verify whether field-relevant concentrations of this drug negatively influence the structure and activity of tropical soil bacteria, plate counts, CO2 efflux measurements, phospholipid fatty acids (PLFA) and community-level physiological profiling (CLPP) profiles were obtained for soil microcosms exposed to 1 or 10 mg kg-1 of MON across 11 days. Although 53% (1 mg kg-1) to 40% (10 mg kg-1) of the MON concentrations added to the microcosms dissipated within 5 days, a subtle concentration-dependent decrease in the number of culturable bacteria (<1 log CFU g-1), reduced (-20 to -30%) or exacerbated (+25%) soil CO2 effluxes, a marked shift of non-bacterial fatty acids, and altered respiration of amines (1.22-fold decrease) and polymers (1.70-fold increase) were noted in some of the treatments. These results suggest that MON quickly killed some microorganisms and that the surviving populations were selected and metabolically stimulated. Consequently, MON should be monitored in agronomic and environmental systems as part of One Health efforts.

Surto de intoxicação por monensina sódica em equinos associada a consumo de suplemento mineral à base de melaço de cana-de-açúcar / Outbreak of monensin sodium poisoning in horses associated with consumption of mineral supplement based on sugarcane molasses

Background: Sodium monensin is a molecule of the group of ionophores antibiotics (IAs) of the polyether carboxylic typeproduced from the fermentation of Streptomyces cinnamonensis. Cases of IA poisoning in animals usually occur accidentally. Fatal poisoning in horses, a non-target species and with particular sensitivity usually occurs by the consumption ofthese products from the toxic dose of 2-3 mg/kg. This report aims to describe the epidemiological and clinical-pathologicalaspects of an outbreak of ionophore antibiotic poisoning in horses due to the consumption of mineral supplementationindicated for ruminants based on sugarcane molasses.Case: Two horses were necropsied. During necropsy, fragments of various organs were collected and fixed in 10% bufferedformalin, routinely processed for histology and stained with hematoxylin and eosin. The information obtained from the animaltrainer was that 19 horses received approximately 25 kg of low moisture mixture based on sugarcane molasses, enriched withmacro and micro minerals, vitamins and additives containing 1000 mg of monensin/kg in the trough. One day after receivingthe product, five horses began to develop ataxia, reluctance to move, difficulty of accompanying the herd and arising. Out ofthe five, three died after three days of evolution, one after six days (equine 1) and another after 15 days (equine 2) [morbidity 26.31%]. At necropsy, diffuse pallor was observed in the gluteus medius, quadriceps femoris, semimembranosus, bicepsbrachii and deep pectoral muscles. Microscopically the muscle fibers were tumefied with hypereosinophilic sarcoplasmof homogeneous appearance and with loss of striations, pynotic or absent nuclei (necrosis). Multifocal areas of fibers withsarcoplasmic fragmentation were observed, with clusters of irregular eosinophilic debris, flake (floct necrosis) or granule(granular necrosis)...

Surto de intoxicação por monensina sódica em equinos associada a consumo de suplemento mineral à base de melaço de cana-de-açúcar / Outbreak of monensin sodium poisoning in horses associated with consumption of mineral supplement based on sugarcane molasses

Background: Sodium monensin is a molecule of the group of ionophores antibiotics (IAs) of the polyether carboxylic typeproduced from the fermentation of Streptomyces cinnamonensis. Cases of IA poisoning in animals usually occur accidentally. Fatal poisoning in horses, a non-target species and with particular sensitivity usually occurs by the consumption ofthese products from the toxic dose of 2-3 mg/kg. This report aims to describe the epidemiological and clinical-pathologicalaspects of an outbreak of ionophore antibiotic poisoning in horses due to the consumption of mineral supplementationindicated for ruminants based on sugarcane molasses.Case: Two horses were necropsied. During necropsy, fragments of various organs were collected and fixed in 10% bufferedformalin, routinely processed for histology and stained with hematoxylin and eosin. The information obtained from the animaltrainer was that 19 horses received approximately 25 kg of low moisture mixture based on sugarcane molasses, enriched withmacro and micro minerals, vitamins and additives containing 1000 mg of monensin/kg in the trough. One day after receivingthe product, five horses began to develop ataxia, reluctance to move, difficulty of accompanying the herd and arising. Out ofthe five, three died after three days of evolution, one after six days (equine 1) and another after 15 days (equine 2) [morbidity 26.31%]. At necropsy, diffuse pallor was observed in the gluteus medius, quadriceps femoris, semimembranosus, bicepsbrachii and deep pectoral muscles. Microscopically the muscle fibers were tumefied with hypereosinophilic sarcoplasmof homogeneous appearance and with loss of striations, pynotic or absent nuclei (necrosis). Multifocal areas of fibers withsarcoplasmic fragmentation were observed, with clusters of irregular eosinophilic debris, flake (floct necrosis) or granule(granular necrosis)... (AU)

Avaliação toxicológica de misturas dos medicamentos veterinários (Monensina, Sulfametazina e Enrofloxacina) em Daphnia magna (Cladocera, Crustacea) / Toxicological evaluation of mixtures of veterinary drugs (Monensin, Sulfamethazine and Enrofloxacin) in Daphnia magna (Cladocera, Crustacea)

Esse trabalho teve como objetivo o estudo da toxicidade aguda e crônica da ação isolada e de misturas binárias de três medicamentos veterinários (Monensina, Sulfametazina e Enrofloxacina) para o organismo teste Daphnia magna. A toxicidade aguda da enrofloxacina determinada foi de CE50 - 54.36 mgL-1, da monensina CE50 - 15.11mgL-1 e da sulfametazina CE50 - 183.80 mgL-1. Para os ensaios de toxicidade crônica foram determinados 3 /"endpoints/" (sobrevivência, reprodução e tamanho do adulto) e foi determinado o CEO para a enrofloxacina de 0,33 mgL-1, da monensina 0,09 mgL-1 e da sulfametazina de 6,8 mgL-1. Para fazer uma comparação entre os testes das substâncias isoladas e das misturas binárias foi utilizado o conceito de unidade tóxica (UT), essa comparação foi feita através da soma das UT dos ensaios individuais e comparando com os resultados dos ensaios de misturas para determinar se houve ação sinérgica, aditiva ou antagônica. O ensaio agudo de mistura monensina/enrofloxacina apresentou ação sinérgica já os ensaios monensina/sulfametazina e sulfametazina/enrofloxacina apresentaram ação antagônica. Os ensaios crônicos de mistura monensina/enrofloxacina e monensina/sulfametazina apresentaram ação sinérgica, porém não foram dosedependente e o ensaio sulfametazina/enrofloxacina apresentou ação antagônica. Com base nesse estudo é possível concluir que a mistura desses medicamentos interfere na sua toxicidade, podendo causar efeitos sinérgicos ou antagônicos.

This work aims to study the acute and chronic toxicity of the isolated and binary mixtures action of three veterinary drugs (Monensin, Sulfamethazine and Enrofloxacin) for the test organism Daphnia magna. The determined acute toxicity of enrofloxacin was EC50 - 54.36 mgL-1, monensin EC50 - 15.11 mgL-1 and sulfamethazine EC50 - 183.80 mgL-1. In the chronic toxicity tests were determined 3 endpoints (survival, reproduction and adult size) and the LOEC determined for enrofloxacina was 0.33 mgL-1, monensin 0.09 mgL-1 and sulfamethazine 6.8 mgL-1. To make a comparison between the tests of isolated substances and binary mixtures it was used the concept of toxic unit (TU), this comparison was made by adding the UT of individual studies and comparing the test results of mixtures to determine whether there was a synergistic action, additive or antagonistic. The acute mixture assay monensin/enrofloxacin showed synergistic action yet the assays monensin/sulfamethazine and sulfamethazine/enrofloxacin showed antagonistic action. The chronic mixing assays monensin / enrofloxacin and monensin / sulfamethazine showed synergistic action, but were not dose-dependent and testing sulfamethazine / enrofloxacin present antagonistic action. Based on this study it can be concluded that the mixing of these drugs interferes with its toxicity, and may cause synergistic or antagonistic effect.

Alterações histopatológicas em músculos e nervos de aves causadas por Monensina e Roxarsona / Microscopic changes in muscles and peripheral nerves of broiler chickens caused by Monensin and Roxarsone

Rações comerciais para frangos de corte geralmente contêm coccidiostáticos na sua fórmula. Um deles, a Monensina, é amplamente utilizado, e quando administrado em doses tóxicas pode levar a lesões nas musculaturas cardíaca e esquelética. A Roxarsona muitas vezes é adicionada à Monensina para potencializá-la, causando lesões em nervos periféricos de aves submetidas ao estresse. Os objetivos desse estudo foram conhecer os efeitos tóxicos da associação das drogas Monensina e Roxarsona em frangos de corte e desenvolver um modelo experimental que permita estudo das lesões macro e microscópicas das musculaturas esquelética e cardíaca e de nervos periféricos. Frangos de corte, pelo seu rápido crescimento e desenvolvimento, foram os animais de escolha. Para tanto, 360 frangos de corte foram divididos em seis grupos experimentais, com três repetições. Diferentes grupos foram tratados com doses crescentes de Monensina, associada ou não à Roxarsona, durante 35 dias. Após esse período as aves foram abatidas e foram colhidos fragmentos das musculaturas cardíaca e esquelética e também nervos periféricos para exame histopatológico. Músculos e nervos de animais tratados com ambas as drogas apresentaram lesões inflamatórias e degenerativas. A intoxicação por Monensina e Roxarsona mostrou ser eficaz como modelo experimental para lesões musculares e nervosas.

Anticoccidial agents are commonly used in the poultry industry. One of them, Monensin, is widely used, and in toxic levels can induce lesions in cardiac and skeletal muscle. Roxarsone can be used in addition to Monensin, increasing its efficacy. Peripheral neuropathy has been shown in chickens that were fed roxarsone supplemented diets and subjected to stress. This paper shows the effects of Monensin in association with Roxarsone in broiler chicken to develop an experimental model that concerns gross and microscopic study of lesions in peripheral nerves and cardiac and skeletal muscle. Broiler chickens are select due to fast growing and developing. 360 chickens distribute in six grups (three repetitions) were fed either with Monensin and/or Roxarsona for a period of thirty five days. The groups were Monensin Oppm/Roxarsone Oppm, Monensin Oppm/Roxarsone 80ppm, Monensin 150ppm/Roxarsone Oppm, Monensin 150ppm Roxarsone 80ppm, Monensin 300ppm/Roxarsone Oppm, Monensin 300ppm /Roxarsone 80ppm. Clinical signs were observed and recorded. After this period, birds were euthanatized and muscles and nerves were removed and submitted to microscopic examination. No gross lesions were observed. The histopathologic findings showed necrosis and myodegeneration in cardiac and skeletal muscle, and macrophages between the fibers. Microscopic lesions were observed in peripheral nerves and cardiac and skeletal muscles consisting in degeneration of and infiltration of inflammatory cells. The use of the association of these drugs in broilers showed to be adequate as a model for nerve and muscle lesions.

Intoxicação experimental por monensina em equinos / Experimental monensin poisoning in horses

Sete eqüinos foram tratados experimentalmente com monensina sódica. Dois desses animais receberem 3-4 kg/eqüino/dia de uma ração comercial sabidamente implicada em surtos naturais da intoxicação por monensina em eqüinos e que continha 180 ppm±20 da droga. Um eqüino recebeu uma única dose de 5 mg/kg e um outro recebeu 4 doses diárias de 1 mg/kg de monensina sódica originária de um premix. Esses quatro eqüinos morreram ou foram sacrificados in extremis, 3-8 dias após o início da administração da droga. Um quinto eqüino recebeu dose única de 5 mg/kg de monensina, ficou levemente doente e se recuperou. Dois eqüinos não desenvolveram sinais da intoxicação. Um desses eqüinos tinha recebido 40 doses diárias de 0,5 mg/kg de monensina e o outro recebeu 3 kg/dia de uma ração da mesma marca que a usada nas fazendas onde surtos de intoxicação por monensina foram detectados (mas de uma outra partida, mais tarde determinada como contendo menos de 5 ppm de monensina). O aparecimento dos sinais clínicos ocorreu de 2 a 5 dias após a administração da droga e a duração do quadro clínico variou de 24 a 76 horas. Os sinais clínicos incluíam taquicardia, arritmia, gemidos, incoordenação, sudorese, decúbito esternal, decúbito lateral, pedaleios e morte. Em cinco dos eqüinos intoxicados observaram-se marcadas elevações da atividade plasmática de creatina fosfoquinase e, em um eqüino, houve leve aumento da atividade plasmática de aspartato aminotransferase. Os principais achados de necropsia consistiram em áreas brancas ou amarelas, focais ou focalmente extensas e bilateralmente simétricas nos músculos esqueléticos...(AU)

Intoxicaçäo experimental por monensina em equinos / Experimental monensin poisoning in horses

Sete eqüinos foram tratados experimentalmente com monensina sódica. Dois desses animais receberem 3-4 kg/eqüino/dia de uma ração comercial sabidamente implicada em surtos naturais da intoxicação por monensina em eqüinos e que continha 180 ppm±20 da droga. Um eqüino recebeu uma única dose de 5 mg/kg e um outro recebeu 4 doses diárias de 1 mg/kg de monensina sódica originária de um premix. Esses quatro eqüinos morreram ou foram sacrificados in extremis, 3-8 dias após o início da administração da droga. Um quinto eqüino recebeu dose única de 5 mg/kg de monensina, ficou levemente doente e se recuperou. Dois eqüinos não desenvolveram sinais da intoxicação. Um desses eqüinos tinha recebido 40 doses diárias de 0,5 mg/kg de monensina e o outro recebeu 3 kg/dia de uma ração da mesma marca que a usada nas fazendas onde surtos de intoxicação por monensina foram detectados (mas de uma outra partida, mais tarde determinada como contendo menos de 5 ppm de monensina). O aparecimento dos sinais clínicos ocorreu de 2 a 5 dias após a administração da droga e a duração do quadro clínico variou de 24 a 76 horas. Os sinais clínicos incluíam taquicardia, arritmia, gemidos, incoordenação, sudorese, decúbito esternal, decúbito lateral, pedaleios e morte. Em cinco dos eqüinos intoxicados observaram-se marcadas elevações da atividade plasmática de creatina fosfoquinase e, em um eqüino, houve leve aumento da atividade plasmática de aspartato aminotransferase. Os principais achados de necropsia consistiram em áreas brancas ou amarelas, focais ou focalmente extensas e bilateralmente simétricas nos músculos esqueléticos...

Effects of monensin feeding during development on female rats and their offspring.

Monensin, a growth-promoting agent and coccidiostat used in veterinary medicine, was studied in terms of its effects on the development of female rats and their offspring when added to the diet. Young female rats received 100 or 300 ppm monensin mixed with powdered chow diet until adulthood, when they were mated and their offspring were evaluated for physical and neurobehavioural development. The data showed that 1) exposure to the higher monensin concentration reduced female body weight; no deaths occurred after exposure to the two monensin concentrations; 2) the offspring of the experimental group receiving 300 ppm monensin presented a weight reduction from 10 to 21 days of lactation; 3) incisor eruption was delayed only in females after exposure to the 100 ppm concentration. We conclude that exposure to monensin during development induces toxicity in female rats and has a notable adverse effect on growth with some limited effects on selective milestones of physical and functional development of the offspring during the postnatal period.