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In the current study, we investigated decreased hatchability and increased embryonic mortality in two farms of layer breeders (flocks A1 and B1) and a farm of broiler breeders (flocks C1 and C2) from Austria, which also presented discoloration of eggshells in 2% of the eggs. After conducting clinical evaluations and the approval that the feed operator was common for flocks A1 and B1, and C1 and C2, it was decided to investigate the feed. Our findings revealed that the feed contained levels of nicarbazin and narasin up to five and 14 times, respectively, above the maximum limits allowed by the European Union for nontarget species. On the other hand, there were no significant abnormalities in vitamin levels, which were also described as the etiology of the noticed abnormalities. Switching to a noncontaminated feed resulted in the clinical signs and production parameters returning to expected ranges. This report emphasizes the significance of considering feed contamination by nicarbazin and narasin as a potential cause of hatchery losses in nontarget species, even in the absence of other clinical signs. Reporte de caso- Pérdidas en la eclosión de parvadas de reproductoras ponedoras y pollos de engorde debido a la contaminación del alimento con nicarbazina y narasina: Reporte de un caso. En el presente estudio, se investigó la disminución de la incubabilidad y el aumento de la mortalidad embrionaria en dos granjas de reproductoras ponedoras (parvadas A1 y B1) y una granja de reproductoras de pollos de engorde (parvadas C1 y C2) de Austria, que también presentaron decoloración del cascarón en el 2% de los huevos. Luego de realizar evaluaciones clínicas y la aprobación de que el operador de alimento era común para las parvadas A1 y B1, y C1 y C2, se decidió investigar el alimento. Nuestros hallazgos revelaron que el alimento contenía niveles de nicarbazina y narasina de hasta cinco y 14 veces, respectivamente, por encima de los límites máximos permitidos por la Unión Europea para especies no objetivo. Por otro lado, no se observaron anomalías significativas en los niveles de vitaminas, lo que también se describió como la etiología de las anomalías observadas. El cambio a un alimento no contaminado provocó que los signos clínicos y los parámetros de producción regresaran a los rangos esperados. Este informe enfatiza la importancia de considerar la contaminación del alimento por nicarbazina y narasina como una causa potencial de pérdidas en la eclosión de especies no objetivo, incluso en ausencia de otros signos clínicos. [ABSTRACT FROM AUTHOR]

To exploit aqueous-soluble formulation and improve the anticoccidial activity of 4,4′-dinitrocarbanilide (DNC, active component of nicarbazin), this paper prepared DNC/GA/PVP K30 solid dispersion (SD) with glycyrrhizic acid (GA) and polyvinylpyrrolidone (PVP) K30 by a mechanical ball milling method without using any organic solvent. Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy were used for the solid state characterization. High performance liquid chromatography, critical micelle concentration, particle characterization, and transmission electron microscopy were used to evaluate the behavior in aqueous solution. In addition, the oral bioavailability, tissue distribution, and anticoccidial activity of DNC/GA/PVP K30 SD were investigated as well. Compared with free drug, the novel formulation not only improved the solubility and dissolution rate of DNC, but also inhibited the fecal output of oocysts and enhanced the therapeutic effect of coccidiosis. According to the experiment results, the DNC/GA/PVP K30 SD increased 4.64-fold in oral bioavailability and dramatically enhanced the concentration in liver which provided a basis for further research in schistosomiasis. In summary, our findings suggested that DNC/GA/PVP K30 SD may have promising applications in the treatment of coccidiosis. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, the Panel on Additives and Products or substances used in Animal Feed (FEEDAP Panel) was asked to deliver a scientific opinion on the efficacy of the coccidiostat nicarbazin (Coxar®) when used in feed for turkeys for fattening. On the basis of the new data provided, the FEEDAP Panel updated its previous conclusions on the efficacy of Coxar® as follows: the two new floor pen studies showed efficacy of nicarbazin from Coxar® reducing the adverse clinical consequences of an Eimeria infection in turkeys. Overall, when considering also the positive floor pen study previously reported and the three positive anticoccidial sensitivity tests, the FEEDAP Panel concludes that Coxar® has the potential to be efficacious against coccidiosis of turkeys for fattening at 100 mg nicarbazin/kg complete feed. [ABSTRACT FROM AUTHOR]

Abstract Following a request from the European Commission, the Panel on Additives and Products or substances used in Animal Feed (FEEDAP Panel) was asked to deliver a scientific opinion on the efficacy of the coccidiostat nicarbazin (Coxar®) when used in feed for turkeys for fattening. On the basis of the new data provided, the FEEDAP Panel updated its previous conclusions on the efficacy of Coxar® as follows: the two new floor pen studies showed efficacy of nicarbazin from Coxar® reducing the adverse clinical consequences of an Eimeria infection in turkeys. Overall, when considering also the positive floor pen study previously reported and the three positive anticoccidial sensitivity tests, the FEEDAP Panel concludes that Coxar® has the potential to be efficacious against coccidiosis of turkeys for fattening at 100 mg nicarbazin/kg complete feed.

Following a request from the European Commission, the Panel on Additives and Products or substances used in Animal Feed (FEEDAP Panel) was asked to deliver a scientific opinion on the safety for the environment of the coccidiostat Coxar® (nicarbazin) when used in feed for turkeys for fattening. In previous assessments, the FEEDAP Panel could not conclude on the safety of Coxar® for the environment due to concerns on 4,40‐dinitrocarbanilide (DNC, one of the moieties of nicarbazin). On the basis of the new data provided, the FEEDAP Panel updates its previous conclusions on the safety of Coxar® for the environment as follows: The use of nicarbazin from Coxar® in complete feed for turkeys does not pose a risk for the terrestrial and aquatic compartment and in sediment. No concern for groundwater is expected. The bioaccumulation potential of nicarbazin in the environment is low. [ABSTRACT FROM AUTHOR]

Abstract Following a request from the European Commission, the Panel on Additives and Products or substances used in Animal Feed (FEEDAP Panel) was asked to deliver a scientific opinion on the safety for the environment of the coccidiostat Coxar® (nicarbazin) when used in feed for turkeys for fattening. In previous assessments, the FEEDAP Panel could not conclude on the safety of Coxar® for the environment due to concerns on 4,40‐dinitrocarbanilide (DNC, one of the moieties of nicarbazin). On the basis of the new data provided, the FEEDAP Panel updates its previous conclusions on the safety of Coxar® for the environment as follows: The use of nicarbazin from Coxar® in complete feed for turkeys does not pose a risk for the terrestrial and aquatic compartment and in sediment. No concern for groundwater is expected. The bioaccumulation potential of nicarbazin in the environment is low.

The aim: to determine the parameters of acute toxicity of the preparative form of an antiemeric agent based on maduramycin and nicarbazine for white mice, white rats and guinea pigs with a single oral administration. Materials and methods. Determination of acute toxicity of the formulation by oral administration was performed on 48 adult male mice, 48 adult nonlinear male rats, 48 adult male guinea pigs. To conduct an experiment on the principle analogues were formed seven experimental and one control group, 6 animal each. The dose of the formulation was calculated individually based on body weight values. It should be noted that the total volume of the emulsion of the formulation administered orally is not exceeded 1.0 cm3per 100 gram b. w. Results. Toxicometric parameters of the formulation were calculated by the method of least squares for probit analysis of mortality curves. It was found that the LD50 of the preparative form of antiemeric agent for white mice for a single oral administration is 238.05±28.08 mg/kg, LD16 - 128.71 mg/kg, LD84 - 347.39 mg/kg, LD100 - 402, 06 mg/kg body weight, respectively. LD50 of the preparative form of antiemeric agent for white rats with a single oral administration is 260.51±28.83 mg/kg, LD16 - 148.39 mg/kg, LD84 - 372.65 mg/kg, LD100 - 428.71 mg/kg body weight, respectively. LD50 of the preparative form of antiemeric agent for guinea pigs for a single oral administration is 275±21.12 mg/kg, LD16 - 201.74 mg/kg, LD84 - 348.25 mg/kg, LD100 - 384.88 mg/kg body weight body respectively. Conclusions. According to SOU 85.2-37-736: 2011 "Veterinary drugs. Determination of acute toxicity" preparative form of a complex antiemeric agent based on maduramycin and nicarbazine on the degree of toxicity can be attributed to moderately dangerous substances (3rd hazard class). [ABSTRACT FROM AUTHOR]

To exploit aqueous-soluble formulation and improve the anticoccidial activity of 4,4′-dinitrocarbanilide (DNC, active component of nicarbazin), this paper prepared DNC/GA/PVP K30 solid dispersion (SD) with glycyrrhizic acid (GA) and polyvinylpyrrolidone (PVP) K30 by a mechanical ball milling method without using any organic solvent. Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy were used for the solid state characterization. High performance liquid chromatography, critical micelle concentration, particle characterization, and transmission electron microscopy were used to evaluate the behavior in aqueous solution. In addition, the oral bioavailability, tissue distribution, and anticoccidial activity of DNC/GA/PVP K30 SD were investigated as well. Compared with free drug, the novel formulation not only improved the solubility and dissolution rate of DNC, but also inhibited the fecal output of oocysts and enhanced the therapeutic effect of coccidiosis. According to the experiment results, the DNC/GA/PVP K30 SD increased 4.64-fold in oral bioavailability and dramatically enhanced the concentration in liver which provided a basis for further research in schistosomiasis. In summary, our findings suggested that DNC/GA/PVP K30 SD may have promising applications in the treatment of coccidiosis.

Abstract Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the coccidiostat Nilablend™ 200G containing lasalocid A sodium and nicarbazin. Nilablend™ 200G is not safe for chickens for fattening at the proposed maximum use level of 50 mg lasalocid A sodium + 50 mg nicarbazin/kg complete feed. Concurrent administration of Nilablend™ 200G (containing lasalocid A sodium) with tiamulin and certain other medicinal substances should be avoided. Lasalocid A sodium has antimicrobial activity against Gram‐positive bacterial species while many Enterobacteriaceae are naturally resistant. Induction of resistance and/or cross‐resistance was not observed in experimental conditions. No information on the interactions of nicarbazin with feed materials, other approved additives or medicinal products have been provided. No data were submitted on the microbiological safety of nicarbazin. The toxicological package for lasalocid A sodium and nicarbazin identified no observed adverse effect levels (NOAELs) that could be the basis for setting health‐based guidance values (e.g. an acceptable daily intake (ADI)). The Panel concluded that a concern for the genotoxicity of nicarbazin in Nilablend™ 200G cannot be excluded and that clarification on the mechanism of action of the test items would be needed. Therefore, the FEEDAP Panel is not in the position to establish an ADI for DNC on which to base the assessment of consumer safety. Nilablend™ 200G is considered toxic by inhalation, corrosive and irritant to eyes, slightly irritant to the skin but not a skin sensitiser. Inhalation exposure is considered a risk to persons handling the additive. The FEEDAP Panel cannot conclude on the safety of Nilablend™ 200G for the environment due to a possible risk for aquatic compartment (freshwater) for DNC. The efficacy of Nilablend® 200G was demonstrated.

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the coccidiostat NilablendTM 200G containing lasalocid A sodium and nicarbazin. NilablendTM 200G is not safe for chickens for fattening at the proposed maximum use level of 50 mg lasalocid A sodium + 50 mg nicarbazin/kg complete feed. Concurrent administration of NilablendTM 200G (containing lasalocid A sodium) with tiamulin and certain other medicinal substances should be avoided. Lasalocid A sodium has antimicrobial activity against Gram-positive bacterial species while many Enterobacteriaceae are naturally resistant. Induction of resistance and/or cross-resistance was not observed in experimental conditions. No information on the interactions of nicarbazin with feed materials, other approved additives or medicinal products have been provided. No data were submitted on the microbiological safety of nicarbazin. The toxicological package for lasalocid A sodium and nicarbazin identified no observed adverse effect levels (NOAELs) that could be the basis for setting health-based guidance values (e.g. an acceptable daily intake (ADI)). The Panel concluded that a concern for the genotoxicity of nicarbazin in NilablendTM 200G cannot be excluded and that clarification on the mechanism of action of the test items would be needed. Therefore, the FEEDAP Panel is not in the position to establish an ADI for DNC on which to base the assessment of consumer safety. NilablendTM 200G is considered toxic by inhalation, corrosive and irritant to eyes, slightly irritant to the skin but not a skin sensitiser. Inhalation exposure is considered a risk to persons handling the additive. The FEEDAP Panel cannot conclude on the safety of NilablendTM 200G for the environment due to a possible risk for aquatic compartment (freshwater) for DNC. The efficacy of Nilablend® 200G was demonstrated. [ABSTRACT FROM AUTHOR]

BACKGROUND Nicarbazin is an anti‐coccidial product sometimes used as a contraceptive to reduce the size of feral pigeon populations. However, its effectiveness in reducing pigeon population size in cities has caused some controversy. Here, we evaluate its effectiveness in the city of Barcelona. RESULTS: In 2017, the Barcelona City Council set 23 feeding stations with nicarbazin and ten with placebo (untreated corn). Censuses were undertaken before and after one year of treatment, within a 200‐m radius around each feeder. We also censused 28 circles of 200 m radius distributed randomly 200 m from the feeders and 28 circles > 500 m from the feeders, which acted as controls. Population size across the whole city was also evaluated pre‐ and post treatment. We found that feral pigeon density did not change after one year of treatment, either in the circles around feeding stations with nicarbazin or in the areas around control stations at 200 and > 500 m from the feeders. Population size in placebo circles rose after a year by 10%. A pigeon census for the whole of Barcelona showed a 10% increase. CONCLUSION: Overall, our results indicate that the nicarbazin treatment had no effect on feral pigeon population size, and we advise against its use as a pigeon control method, at least in large cities. [ABSTRACT FROM AUTHOR]

This study describes a three-year evaluation (2017–2019) of a fertility control protocol using nicarbazin (Ovistop®) to reduce the abundance of the most conflictive colonies of feral pigeon, Columba livia var. domestica, in Barcelona, Spain, as a long-term strategy based on animal welfare. The treatment was supplied to 34 pigeon colonies by automatic hopper feeders installed in public areas. A superiority study and a population monitoring study were carried out to evaluate differences in the abundance of the colonies, as well as the proportion of juveniles, the possible intake of nicarbazin by non-target species and the movement of individuals among colonies. The results showed statistical differences in the population trends between the test (−22.03%) and control (+12.86%) groups, and a significant steady decreasing trend in the pigeon abundance (−55.26%) was registered until the end of 2019. The proportion of juveniles was significatively lower in the test colonies, and a non-target species (Eurasian collared doves, Streptopelia decaocto) was observed consuming in a residual form. The protocol using nicarbazin is able to both control the abundance of pigeons, with no impact over non-target species, and respond to the public interest about animal welfare by providing an ethical method to manage overabundant and/or conflictive populations.

Abstract Following a request from the European Commission, the Panel on Additives and Products or substances used in Animal Feed (FEEDAP Panel) was asked to deliver a scientific opinion on the safety and efficacy of the coccidiostat Monimax® (monensin sodium and nicarbazin) when used in feed for turkeys or chickens for fattening. In previous assessments (2017, 2018), the FEEDAP Panel could not conclude on the safety of Monimax® for the environment due to concerns on monensin sodium and 4,4′‐dinitrocarbanilide (DNC, one of the moieties of nicarbazin). The applicant provided additional information that has been assessed. The use of monensin sodium from Monimax® in complete feed for chickens for fattening, chickens reared for laying and turkeys for fattening poses no risk for the aquatic compartment, the terrestrial compartment or for sediment. The bioaccumulation potential of monensin in the environment is low. No concerns would arise for the 4,6‐dimethylpyrimidin‐2‐ol (HDP) moiety of nicarbazin excreted from chickens for fattening, chickens reared for laying and turkeys fed Monimax®. The use of DNC moiety of nicarbazin from Monimax® in complete feed for chickens for fattening, chickens reared for laying and turkeys for fattening poses no risk for the aquatic compartment, the terrestrial compartments or for sediment. The bioaccumulation potential of DNC in the environment is low and the risk for secondary poisoning is not likely to occur

This study outlines the successful development and testing of an immunochromatographic test strip for the detection of the anticoccidial drug, nicarbazin in milk. The preparation and characterization of an anti-4,4′-dinitrocarbanilide monoclonal antibody was based on hapten re-4,4′-dinitrocarbanilide. The monoclonal antibody was highly specific for 4, 4′-dinitrocarbanilide, with a half-life inhibitory concentration (IC50) of 3.46 ng/mL. The detection limit was 0.86 ng/mL. The linear range was 1.71–7 ng/mL. The cut-off values of colloidal gold-based immunochromatographic test paper in phosphate buffered saline (PBS) and in milk were 10 ng/mL, 100 ng/mL, respectively. These results were in good agreement with ELISA analyses and suggest that immunochromatographic test strips are a fast and sensitive method for the semi-quantitative and qualitative analysis of nicarbazin in milk.

A clinical study was made into the abilities of nicarbazin and monensin and a nicarbazin + monensin combination to control Eimeria acervulina, E. maxima, and E. tenella in chickens. When included in the feed, at concentrations of 40 ppm nicarbazin or 40 ppm monensin, these products showed partial efficacy evaluated by daily weight gain (DWG) but no activity judged by daily feed intake (DFI) or feed conversion ratio (FCR). By contrast, the combination of 40 ppm nicarbazin + 40 ppm monensin provided complete control of infection judged by greater DWG and DFI, and lower FCR. Monensin at a concentration of 40 ppm was ineffective in preventing lesions caused by all three species. Nicarbazin at a concentration of 40 ppm was unable to suppress lesions of E. acervulina and E. maxima but was able to suppress lesions caused by E. tenella. Nicarbazin 40 ppm + monensin 40 ppm suppressed lesions of all three species. RESEARCH HIGHLIGHTS Nicarbazin or monensin at 40 ppm gave only partial control of Eimeria spp. A combination of 40 ppm nicarbazin + 40 ppm monensin controlled DWG, DFI and FCR. Nicarbazin or monensin at 40 ppm did not suppress all Eimeria spp. lesions. Nicarbazin 40 ppm + monensin 40 ppm suppressed lesions of all three species. [ABSTRACT FROM AUTHOR]

Eared doves (Zenaida auriculata) may cause up to 50% of losses in some damaged crops. The objective of this study was to measure a contraceptive bait (nicarbazin pellets 0,5%) acceptance by Eared Doves in individual cages (10 birds/treatments). After quarantine and an adaptation period to the cages, the bait (nicarbazin pellets 0,5%) was offered to the doves for four hours per day for 21 consecutive days in three formulations (treatments) according to the bait: (1) OvoControlS® developed for sparrows; (2) OvoControlS® mixed with cracked corn in a 78:22 ratio; (3) was offered the corresponding bait treatment, cracked OvoControlP® elaborated for rock pigeon (Columba livia). Every morning each bird was offered the bait of the treatment, and in the afternoon a maintenance diet was offered in the same amount and daily consumption was registered. The average consumption/week of OvoControlS® and OvoControlS® with corn was less than 1.0g. Cracked OvoControlP® bait was accepted by birds. The consume increased in weeks 2 and 3 (p<0.05), exceeding 1.0 g average/week and was higher than the other formulations (p<0.05). It can be concluded that this treatment was accepted and consumed by eared doves in captivity in amounts that could cause an effect on this species reproduction. [ABSTRACT FROM AUTHOR]

Nicarbazin is an anticoccidial used in poultry production. Its residue of concern left in chicken meat is 4,4′-dinitrocarbanilide (DNC) whose content can be reduced through meat thermal processing. Thermal analysis techniques can be considered to elucidate how DNC degradation proceeds. This study aimed to investigate the thermal behavior of DNC using TG–DSC–MS and Py–GC–MS. TG–DSC–MS data showed that DNC decomposition occurs in a single step (252–280 °C) as an endothermic event (ΔH of 670 J g−1). Fragments detected at m/z 43, 44 and 65 indicated the release of isocyanic acid, carbon dioxide and 4-nitroaniline as breakdown products. In addition, Py–GC–MS analysis confirmed that DNC is thermally degraded above 250 °C generating 4-nitrophenyl isocyanate and 4-nitroaniline as the major pyrolysis products. Findings obtained from thermal analysis herein are useful to better comprehend the DNC disappearance after submitting chicken meat to heat processing. [ABSTRACT FROM AUTHOR]

Originally developed as a remote trail camera system for monitoring deer, ERS Group of Atlanta, GA has combined the advantages of digital imaging together with cellular telephone technology into a “Smart Scouter™”. By combining a motion and heat sensing digital camera, this system can record movement at the target site and upload the images immediately to both a website and email providing real time monitoring details. We describe the use of the Smart Scouter™ camera system for monitoring pigeon numbers and non-targets feeding at site where OvoControl® P bait was applied, without intervention by technicians. The camera system can augment required monitoring when applying OvoControl® P bait. It is especially useful in remote or hard-to-access areas, and can save time and labor costs.

OvoControl G® is a relatively new product that reduces the hatchability of Canada goose (Branta canadensis) eggs. However, little data is available on the cost of application. We present a model for estimating the cost of application of OvoControl G for managing nuisance Canada goose populations and compare that model to the cost and results of field-based 2 applications in Oregon. Our model showed that at low goose densities, fixed labor costs are responsible for a significant portion of the total cost. As goose densities increase, these fixed costs become equivalent to, and eventually less than, the costs associated with the purchase of the product. As we expected from the model, the cost of applying OvoControl is high compared to the actual reduction in reproduction. However, even with this apparently high cost, cooperators were pleased with the results. We also present several scenarios that managers may employ to further reduce the cost of application.

Effective methods for managing populations of rock pigeons and other overabundant avian species are limited. An alternative to lethal control is reproductive inhibition. Nicarbazin is a widely used additive in poultry feed that also reduces hatchability of eggs. It is the active ingredient in OvoControl®G, a bait product recently registered as a means for reducing hatchability of eggs of urban Canada geese. In a series of trials with captive pigeons, we evaluated the effectiveness of several nicarbazin bait formulations to determine effects on reproduction and to quantify levels of nicarbazin absorbed into the blood. Although pigeons readily accepted a scaled-down version of the OvoControl goose bait, this formulation did not adequately reduce hatchability because of insufficient absorption of nicarbazin into the blood. Other bait formulations that contained 2,500 ppm nicarbazin produced similar results. Only bait formulated with 5,000 ppm nicarbazin produced sufficient amounts of the active ingredient in blood plasma of test birds. Eventual registration of the nicarbazin pigeon bait will provide additional management options for limiting growth of unwanted pigeon populations.

Avian contraception is a nonlethal management tool that can be utilized in conjunction with other management techniques to help manage bird populations causing damage. Because management situations vary with respect to the type of damage, species involved, location, and nontarget hazards, it is necessary to develop multiple contraceptive tools to allow management flexibility. DiazaCon™ and nicarbazin have already been developed at the National Wildlife Research Center as avian contraceptives. Although both of these are promising contraceptive agents, more are needed for a wider variety of situations. Current research is focusing on other cholesterol inhibitors, inhibitors of the P450 side chain cleavage enzyme, and aromatase inhibitors. Because cholesterol is needed for steroid reproductive hormone production, inhibition of cholesterol impairs reproduction by preventing the formation of the necessary hormones. The P450 side chain cleavage enzyme is needed to convert cholesterol to pregnenolone, the precursor to progesterone and testosterone. Progesterone is needed for egg formation, ovulation, and oviposition, and testosterone is needed for sperm production. Aromatase is needed to convert testosterone to estradiol, which is needed in females to stimulate the production of egg yolk precursors in the liver. Inhibition of either of these enzymes should result in impaired reproduction. In the future, natural plant products with contraceptive activity, such as neem seed, will also be investigated. Because development of avian contraceptives is time intensive, an efficient screening process needs to be in place. Population models can assist in choosing specific agents to test for a given species and management situation. Although contraception is unlikely to be useful as a stand-alone tool, it can be included in integrated management plans.

We evaluated our ability to deliver adequate daily doses of the reproductive inhibitor, nicarbazin, to individually marked resident Canada geese (Branta canadensis). We also evaluated the efficiency of nicarbazin in reducing egg hatchability. The study was conducted prior to and during the egg-laying period at a wildlife sanctuary that has a large, problem-causing population of resident geese that were accustomed to being fed by people. Twenty-eight adult females were marked with individually identifiable neck collars, 24 of which were affixed with radio transmitters. Grit pellets and gelatin capsules containing nicarbazin were fed to these geese from March 17, 2001 through April 26, 2001. We attempted to deliver doses to geese each day. Doses varied among geese throughout the study and within geese daily because all geese were not present at the site each day, and even if present they accepted the bait to varying degrees. Seven of our target birds did receive what we believed to be adequate doses of nicarbazin. We documented that only about 11% of the resident population nested at the sanctuary, while the others nested in remote areas. We were able to locate 5 nests of birds that received adequate doses, but found no significant effect of nicarbazin on the hatchability of their eggs compared to untreated geese. We found that the biggest challenges to orally-fed reproductive inhibitors include the palatability of bait relative to other food sources, reduced feeding during the breeding period, and movements and territoriality associated with nesting.

Abstract Following the request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the proposed modification of the terms of the authorisation regarding the maximum inclusion level of Maxiban® G160. The FEEDAP Panel cannot conclude on the safety of Maxiban® G160 at a dose level of 70 + 70 mg/kg feed for the target species. The use of Maxiban® G160 in diets for chickens for fattening at the maximum proposed dose complies with the maximum residue levels (MRLs) in force of narasin and 4,4’‐dinitrocarbanilide (DNC) at 0‐day withdrawal except for DNC in kidney which was slightly above the MRL. Compliance with DNC MRLs was seen in all tissues at 1‐day withdrawal. Based on the available data, the FEEDAP Panel cannot conclude on the safety of Maxiban® G160 for the environment due to the risk identified for the terrestrial organisms due to DNC. Moreover, the high persistence and hydrophobicity of DNC indicate that there might be a risk for bioaccumulation but the risk for secondary poisoning was not identified. The potential of DNC to accumulate in soil over the years should be investigated by monitoring in a field study. The FEEDAP Panel would not be in the position to conclude on the efficacy of Maxiban® G160 in chickens for fattening based on the data provided for the dose of 40 + 40 mg narasin + nicarbazin/kg feed.

Abstract The coccidiostat Monimax® (monensin sodium and nicarbazin) is considered safe for chickens for fattening and chickens reared for laying at the highest use level of 50 mg monensin and 50 mg nicarbazin/kg complete feed. This conclusion is extended to chickens reared for laying. For both active substances, the metabolic pathways in the chicken are similar to those in the turkey and rat. Nicarbazin, when ingested, is rapidly split in its two components dinitrocarbanilide (DNC) and 2‐hydroxy‐4,6‐dimethylpyrimidine (HDP) which behave independently. Monimax® does not represent a genotoxic risk. No safety concerns would arise from the nicarbazin impurities p‐nitroaniline and methyl(4‐nitrophenyl) carbamate. The lowest no observed effect level (NOEL) identified for monensin sodium in a developmental study in rabbits is 0.3 mg monensin sodium/kg body weight (bw) per day for maternal toxicity in rabbits. The lowest no observed adverse effect level (NOAEL) identified in a 52‐week study in rat using DNC + HDP was 20 mg DNC + 8 mg HDP/kg bw per day based on the absence of microcrystals in urine and related microscopic renal observations. No significant interaction between monensin sodium and nicarbazin is expected from toxicological studies. The use of Monimax® at the highest proposed dose will not pose a risk to persons consuming animal products from treated chickens for fattening. This conclusion is extended to chickens reared for laying. No withdrawal time is required for Monimax® in chickens for fattening. Residue data comply with the established maximum residue limits (MRLs) for monensin and DNC. Based on the available data, the FEEDAP Panel cannot conclude on the safety of Monimax® for the environment. Monimax® has the potential to control coccidiosis in chickens for fattening at a minimum concentration of 40 mg monensin and 40 mg nicarbazin/kg complete feed.

Highlights • A simple and sensitive UPLC/HRMS method for the evaluation of 17 anticoccidials in eggs and poultry. • Use of experimental designs to evaluate and optimize the performance of the HRMS method. • Method validation according to the Commision Decision 2002/657/EC. • Assessment of anticoccidials within a monitoring program. Abstract A new sensitive and selective multi-residue method based on liquid chromatography - Orbitrap high resolution mass spectrometry (LC-Orbitrap-HRMS) was developed and validated for the determination of 17 anticoccidials in poultry and eggs. Instrumental parameters were optimized by the means of statistical experimental designs to improve the sensitivity, precision, and repeatability of the method. Further optimization of auto-tuned MS parameters led to an increase of signal intensity by 10% to 99% for 16 out of 17 analytes. The sample preparation procedure included extraction from muscle tissue and egg samples with acetonitrile, followed by preconcentration, reconstitution, and filtration. Validation was performed according to the Commission Decision 2002/657/EC. The occurrence of anticoccidials in eggs and poultry was assessed by using the developed analytical procedure within the Latvian national monitoring program, revealing quantifiable residues for 6 analytes (marker residue of nicarbazin - 4,4′-dinitrocarbanilide (DNC), salinomycin, narasin, toltrazuril, and its two metabolites). [ABSTRACT FROM AUTHOR]

This study outlines the successful development and testing of an immunochromatographic test strip for the detection of the anticoccidial drug, nicarbazin in milk. The preparation and characterization of an anti-4,4′-dinitrocarbanilide monoclonal antibody was based on hapten re-4,4′-dinitrocarbanilide. The monoclonal antibody was highly specific for 4, 4′-dinitrocarbanilide, with a half-life inhibitory concentration (IC50) of 3.46 ng/mL. The detection limit was 0.86 ng/mL. The linear range was 1.71-7 ng/mL. The cut-off values of colloidal gold-based immunochromatographic test paper in phosphate buffered saline (PBS) and in milk were 10 ng/mL, 100 ng/mL, respectively. These results were in good agreement with ELISA analyses and suggest that immunochromatographic test strips are a fast and sensitive method for the semi-quantitative and qualitative analysis of nicarbazin in milk. [ABSTRACT FROM AUTHOR]

Veterinary pharmaceuticals are widely used as food additives in the poultry industry, and the unknown consequences of releasing these compounds into the environment are of concern. The purpose of the present study was to determine the direct impact of 2 veterinary pharmaceuticals (nicarbazin and monensin), commonly used in the poultry industry, on nontarget invertebrates and plant species. Ecotoxicological tests were used to evaluate the acute and chronic toxicity in earthworms (Eisenia andrei), collembolans (Folsomia candida), and 2 plant species (Brassica rapa and Triticum aestivum). Chemical analytical measurements were in good agreement with the nominal concentrations used, although some variability was seen. The results obtained showed no effects of nicarbazin at the highest nominal tested concentration of 1000 mg a.i./kg soil dry weight on any of the organisms, whereas exposure to monensin caused a concentration‐specific response pattern. Species sensitivity to monensin decreased in the following rank order: B. rapa > T. aestivum > E. andrei > F. candida, with measured median effect concentrations (based on soil exposure) ranging between approximately 10 and 120 mg/kg. Our results emphasize the importance of using a test battery when assessing ecotoxicological effects by using different ecophysiological endpoints and species from different trophic levels. Environ Toxicol Chem 2018;37:3145–3153. © 2018 SETAC [ABSTRACT FROM AUTHOR]

Abstract The coccidiostat Coxar® is safe for turkeys for fattening at the use level of 100 mg nicarbazin/kg complete feed, with a margin of safety of about 1.25. Nicarbazin, when ingested, is rapidly split in its two components 2‐hydroxy‐4,6‐dimethylpyrimidine (HDP) and dinitrocarbanilide (DNC), which behave independently. HDP‐related residues are much lower than those of DNC. DNC is the marker residue. Liver is the target tissue. Nicarbazin is not genotoxic. The primary toxicity resulting from the oral use of nicarbazin is renal toxicity. The lowest no observed adverse effect level (NOAEL) identified in a 52‐week study in rat using DNC+HDP is 20 mg DNC + 8 mg HDP/kg body weight (bw) per day based on the absence of microcrystals in urine and related microscopic renal observations. The use of 100 mg nicarbazin from Coxar®/kg complete feed for turkeys for fattening will not pose a risk to consumers, provided that maximum contents in nicarbazin of 0.1% p‐nitroaniline (PNA) and 0.4% methyl(4‐nitrophenyl) carbamate (M4NPC) would be respected. No withdrawal time is required. Residue data comply with the established maximum residue limits (MRLs). Nicarbazin is not a skin or eye irritant and not a skin sensitiser. These conclusions also apply to the additive Coxar®. Inhalation toxicity of nicarbazin is limited; the granulated additive has a low dusting potential. No risk for users is identified. Based on the available data, the FEEDAP Panel cannot conclude on the safety of Coxar® for the environment. The efficacy of 100 mg nicarbazin from Coxar®/kg feed was demonstrated in three anticoccidial sensitivity tests (AST), but only in one floor pen study. The floor pen study with 75 mg nicarbazin failed to demonstrate evidence of efficacy. No final conclusions on the efficacy of nicarbazin from Coxar® for turkeys for fattening can be drawn.

Abstract The coccidiostat Monimax® (monensin sodium and nicarbazin) is considered safe for turkeys for fattening at the highest use level of 50 mg monensin and 50 mg nicarbazin/kg complete feed. The simultaneous use of Monimax® and certain antibiotic drugs (i.e. tiamulin) is contraindicated. For both active substances, the metabolic pathways in the chicken are similar to those in the turkey and rat. Nicarbazin, when ingested, is rapidly split in its two components dinitrocarbanilide (DNC) and 2‐hydroxy‐4,6‐dimethylpyrimidine (HDP) which behave independently. Monimax® does not represent a genotoxic risk. No safety concerns would arise from the nicarbazin impurities p‐nitroaniline and methyl(4‐nitrophenyl) carbamate. The lowest no observed effect level (NOEL) identified for monensin sodium in a developmental study in rabbits was 0.3 mg monensin sodium/kg body weight (bw) per day for maternal toxicity in rabbits. The lowest no observed adverse effect level (NOAEL) identified in a 52‐week study in rat using DNC + HDP was 20 mg DNC + 8 mg HDP/kg bw per day. No significant interaction between monensin sodium and nicarbazin is expected from toxicological studies. The use of Monimax® at the highest proposed dose will not pose a risk to persons consuming animal products from treated turkeys for fattening. No withdrawal time is required for Monimax® in turkeys for fattening. Residue data comply with the established maximum residue limits for monensin and DNC. Monensin sodium presents a hazard by inhalation and may also be associated with dermal toxicity. Monimax® is not a skin irritant; however, no data are available for the eye irritation potential of monensin. Monimax® is not a skin sensitiser. Based on the available data, the FEEDAP Panel cannot conclude on the safety of Monimax® for the environment. Monimax® has the potential to control coccidiosis in turkeys for fattening at a minimum concentration of 40 mg monensin and 40 mg nicarbazin/kg complete feed.

Chicken coccidiosis can cause severe enteritis with high mortality, which causes serious economic losses to the global breeding industry each year. The most virulent species is Eimeria tenella (E. tenella), but the infectivity of different E. tenella varies among geographic strains. At present, there are no reports related to the pathogenicity and drug resistance of E. tenella in Yiwu, Zhejiang province, China. A total of 600 fecal samples were collected from 10 farms in Zhejiang province, the overall oocyst prevalence was 54.2% (325/600). The prevalence was significantly higher (P < 0.01) in chickens under 40 d (97.5%) than that in chickens between 60 and 85-days-old (40.5%) and chickens over 90-days-old (24.5%). E. tenella stain was isolated from fecal samples of chickens in Yiwu and the pathogenicity of this isolate was determined, and then we recorded the survival rate, bloody stool score, lesion score, average weight gain. The results showed that all of the chickens infected with 5 × 10 5 sporulated oocysts of E. tenella died after the seventh day of infection, the bloody stool score and average lesion score of chickens from group 1 (5 × 10 5 ), group 2 (5 × 10 4 ), group 3 (5 × 10 3 ) and group 4 (5 × 10 2 ) decreased successively; the average weight gain (g) and relative weight gain (%) increased successively; the weight gain of the low-dose E. tenella infection groups (5 × 10 3 and 5 × 10 2 ) were higher than the other 2 groups (5 × 10 5 and 5 × 10 4 ) (P < 0.05). Finally, The E. tenella isolate was tested for sensitivity to 6 anticoccidial drugs (sulfachloropyrazine sodium, amproline, toltrazuril, clopidol, salinomycin, and nicarbazine) using 4 indexes including anticoccidial index(ACI), percent of optimum anticoccidial activity (POAA), reduction of lesion scores (RLS), and relative oocyst production (ROP). The results showed that this isolate has developed severe resistance to drugs of salinomycin and nicarbazine, moderate resistance to amproline and clopidol, slight resistance to toltrazuril, while the E. tenella isolate performed more sensitive to sulfachloropyrazine sodium., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Abstract: For the first time, a robust electrochemical sensor to detect the coccidiostat nicarbazin (NCZ) is developed through the green synthesis of Prussian blue cubes from Volvariella volvacea (paddy straw mushroom) extract. Recently, numerous articles were reported about the issue that the prophylactic drugs were injected excessively as a feed additive for fattening the chickens in short period. It is a significant concern that the level of coccidiostat NCZ exceeds the residue limits in the tissues of the meat; mainly, in chicken and eggs. Therefore, it is crucial to develop a sensitive, reproducible and long‐lasting sensor for the real‐time detection of NCZ. Thus, we have generated an electrochemical sensor through the economic screen‐printed carbon electrode (SPCE) modification method. Eco‐friendly Prussian blue cubes are fabricated on the carbon film of SPCE. As a result, the modified electrode showed exceptional electrocatalytic ability towards NCZ and the reduction peak currents are correlated to the concentrations of NCZ. It retains the more extensive working range between 1.25×10−7 to 1.53×10−3 mol L−1, and it possesses a very low limit of detection as well as the appreciable sensitivity. This method is successfully applied to the recognition of NCZ in the samples of chicken meat and eggs. [ABSTRACT FROM AUTHOR]

Carryover of medicated feed additives between batches of feed can potentially result in harmful drug residues in the edible tissues of food-animals. Flushing the equipment with an ingredient, such as ground grain, is one method used to remove any residual medicated feed from the system. It is generally recommended that the quantity of flush used be between 50 and 100 g/kg of the mixer’s capacity. However, there is little data that supports this recommendation. Therefore, an experiment was conducted to determine the minimum quantity of flush material required to prevent drug carryover; and to quantify the interrelationship between flush size and drug concentration. The feed medicated with nicarbazin (Nicarb 250 g/kg®; 00.125 g/kg) was manufactured and conveyed from the mixer, through a drag conveyor and bucket elevator, and placed into a finished product bin. The system was then flushed using ground corn in the amount of 25, 50, 100, 150, or 200 g/kg of the mixer’s capacity (454.5 kg). Subsequently, a non-medicated diet was conveyed through the system and samples were collected and analyzed for nicarbazin. No differences were detected among the flush treatments, and all treatments were effective in reducing nicarbazin carryover to less than 2.2 mg/kg to the non-medicated diet. Collectively, these studies demonstrate that existing flushing guidelines meet or exceed what is required to prevent carryover of medicated feed additives. [ABSTRACT FROM AUTHOR]

In this work, a platinum group metal-free (PGM-free) catalyst based on iron as transitional metal and Nicarbazin (NCB) as low cost organic precursor was synthesized using Sacrificial Support Method (SSM). The catalyst was then incorporated into a large area air-breathing cathode fabricated by pressing with a large diameter pellet die. The electrochemical tests in abiotic conditions revealed that after a couple of weeks of successful operation, the electrode experienced drop in performances in reason of electrolyte leakage, which was not an issue with the smaller electrodes. A decrease in the hydrophobic properties over time and a consequent cathode flooding was suspected to be the cause. On the other side, in the present work, for the first time, it was demonstrated the proof of principle and provided initial guidance for manufacturing MFC electrodes with large geometric areas. The tests in MFCs showed a maximum power density of 1.85 W m −2 . The MFCs performances due to the addition of Fe-NCB were much higher compared to the iron-free material. A numerical model using Nernst-Monod and Butler-Volmer equations were used to predict the effect of electrolyte solution conductivity and distance anode-cathode on the overall MFC power output. Considering the existing conditions, the higher overall power predicted was 3.6 mW at 22.2 S m −1 and at inter-electrode distance of 1 cm. [ABSTRACT FROM AUTHOR]

Abstract Following a request from European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the proposed modification of the terms of the authorisation regarding the formulation of the product Maxiban® G160 (narasin and nicarbazin). The applicant has proposed to modify the concentration of Microtracer‐F‐Red in the additive from the currently authorised 11 g/kg to a range of 4–11 g/kg. Based on data submitted on the composition and the stability, the FEEDAP Panel concluded that the physicochemical properties of the additive were not affected by the proposed modification. Therefore, the assessment of safety and efficacy made for the former formulation with 11 g Microtracer‐F‐Red/kg is still valid for the newly applied formulation.

This review presents up-to-date information about current research on nicarbazin, one of the most used anticoccidials in poultry production. The focus is to elucidate regulation concerning nicarbazin, limits for its residues in food, how maximum residue limits in different countries are calculated regarding edible chicken tissues and the possible implications in human health. Analytical methods to extract and quantify this residue, expressed as dinitrocarbanilide (DNC) are presented and discussed, including qualitative screening and quantitative/confirmatory analytical methods. Monitoring results and occurrence of DNC residues in chicken meat are discussed. Additionally, the causes of eventual chicken meat contamination and possible solutions to reduce or eliminate DNC residue in tissues are also presented. The paper concludes with perspectives, the current state of DNC residue analysis and suggestions for future research, especially considering the gap in the study of residue recycling effect due to continuous chicken litter use. [ABSTRACT FROM AUTHOR]

The depletion times of the anticoccidial nicarbazin administered individually and of nicarbazin and narasin administered in combination were evaluated by determining the presence and levels of 4,4'-dinitrocarbanilide (DNC), the marker residue for nicarbazin, and narasin residues in the muscle tissues of broiler chickens subjected to a pharmacological treatment. A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was used. The results showed the presence of all anticoccidial residues; however, the DNC levels were higher when the nicarbazin was administered individually than when it was used in association with narasin throughout the experimental period. After six days of withdrawal, the DNC level following nicarbazin administration alone was lower than the maximum residue level (MRL) of 200 μg kg-1. However, when the nicarbazin was co-administered with narasin, the concentrations of DNC were lower than the MRL after four days of withdrawal. These results may be justified because the dosage of nicarbazin, when administrated individually, is greater than when it is used in combination with narasin. The levels of narasin were lower than the MRL of 15 μg kg-1 throughout the evaluation period. It was concluded that nicarbazin is rapidly metabolized from the broiler muscles up to six days of withdrawal since the DNC levels were lower than the maximum residue level (MRL) and the concentrations of narasin were lower than the MRL throughout the evaluation period. [ABSTRACT FROM AUTHOR]

Ten reference genes were investigated for normalization of gene expression data in the shell gland of laying hens. Analyses performed with geNorm revealed that hypoxanthine phosphoribosyltransferase 1 (HPRT1) and hydroxymethylbilane synthase (HMBS) were the two most stable reference genes in response to post-oviposition time alone (POT) or with nicarbazin treatment (POT+N) of laying hens. NormFinder analyses showed that the two most stable reference genes in response to POT and POT+N were 18S ribosomal RNA (18S rRNA), ribosomal protein L4 (RPL4) and HMBS, RPL4, respectively. BestKeeper analyses showed that 18S rRNA, RPL4 and HPRT1, HMBS were the two most stable reference genes for POT, and POT+N, respectively. Of the ten reference genes, all except B2M showed geNorm M <0.5, suggesting that they were stably expressed in the shell gland tissue. Consensus from these three programs suggested HPRT1 and HMBS could be used as the two most stable reference genes in the present study. Expression analyses of four candidate target genes with the two most and the two least stable genes showed that a combination of stable reference genes leads to more discriminable quantification of expression levels of target genes, while the least stable genes failed to do so. Therefore, HMBS and HPRT1 are recommended as the two most stable reference genes for the normalization of gene expression data at different stages of eggshell formation in brown-egg laying hens. Available statistical programs for reference gene ranking should include more robust analysis capability to analyse the gene expression data generated from factorial design experiments. [ABSTRACT FROM AUTHOR]

A series of 4 floor pen studies was conducted to evaluate the effects of environmental temperature modification on nicarbazin (NIC) responses in broiler chickens raised to 28 d of age. Birds were reared at either standard temperatures (recommended by the primary breeder for ages zero to 28 d) or at 3°C below this level. From placement to 28 d, birds were provided feeds containing zero, 100, or 125 ppm NIC, comprising a 2 × 3 factorial arrangement in each test. Two of the trials were conducted in the presence of an imposed coccidial challenge and 2 were conducted in healthy animals. At 18 and 28 d of age, performance was recorded; cloacal temperatures were measured at 7, 14, 21, and 26 days. Mortality data were collected daily and coccidial lesions were scored at 6 d post challenge. Results of these studies revealed that NIC improved coccidial lesion scores regardless of environmental temperature. In the absence of coccidial challenge, NIC depressed performance, but reductions in environmental temperature diminished the magnitude of these responses. Under conditions of coccidial challenge, NIC significantly improved body weight gains in both temperature environments. Compared to standard temperature conditions, lower environmental temperatures exerted a positive effect on feed conversion rates of NIC-fed broilers. Birds reared in the low temperature environment exhibited lower cloacal temperatures than standard environment groups throughout the test period. Irrespective of coccidial challenge, lower environmental temperatures significantly reduced nicarbazin mortality compared to standard temperature groups, resulting in a significant nicarbazin x temperature interaction. This finding indicates that temperature modification is a practical method for minimizing mortality over the course of 28-day nicarbazin usage. [ABSTRACT FROM AUTHOR]

The purpose of this study was an experimental investigation and a statistical evaluation of the influence of various additives in feed mixtures of broiler chickens on fatty acids content and their ratio in breast and thigh muscles. First feed additive consisted of narasin, nicarbasin and salinomycin sodium, and other five additives were of phytogenic origin.In vivoexperiment was realized on the poultry experimental station with deep litter breeding system. A total of 300 one-day-old hybrid chickens Cobb 500 divided into six groups were used for the experiment. The experimental period was divided into four phases, i.e. Starter, Grower 1, Grower 2 and Final, according to the application of commercial feed mixture of soy cereal type. Additive substances used in feed mixtures were different for each group. Basic feed mixtures were equal for all groups. Fatty acid profile of breast and thigh muscles was measured by the method of FT IR Nicolet 6700. Investigated additive substances in the feed mixtures did not have statistically significant effect on fatty acid content and omega-6/omega-3 polyunsaturated fatty acid (PUFA) ratio in breast and thigh muscles. Strong statistically significant relation between omega-6 PUFAs and total PUFAs were proved by experiment. A relation between omega-3 PUFAs and total PUFAs was found only in the group with Biocitro additive. [ABSTRACT FROM PUBLISHER]

The determination of the dissociation constant of 2-hydroxy-4,6-dimethylpyrimidine in nicarbazin was carried out by means of capillary electrophoresis using a dynamic coating of a fused-silica capillary with high-molecular-mass poly(diallyldimethylammonium chloride) (PDDA) implementing two methods: (a) fitting the effective mobility determined from different electrophoretic runs at a single wavelength as a function of pH and (b) a novel modeling strategy of the spectrophotometric second-order data generated with the diode array detector at several wavelengths as a function of pH. The accuracy of the proposed methodologies was verified using robenidine as a model compound with known value of pKa. [ABSTRACT FROM AUTHOR]

Coxar® is safe for turkeys for fattening at the use level of 100 mg nicarbazin/kg complete feed, with a margin of safety of about 1.25. Nicarbazin, when ingested, is rapidly split in its two components 2-hydroxy-4,6-dimethylpyrimidine (HDP) and dinitrocarbanilide (DNC), which behave independently. HDP-related residues are much lower than those of DNC. DNC is the marker residue. Liver is the target tissue. Nicarbazin is not genotoxic. The primary toxicity resulting from the oral use of nicarbazin is renal toxicity. The lowest no observed adverse effect level (NOAEL) identified in a 52-week study in rat using DNC+HDP is 20 mg DNC + 8 mg HDP/kg body weight (bw) per day based on the absence of microcrystals in urine and related microscopic renal observations. The use of 100 mg nicarbazin from Coxar®/kg complete feed for turkeys for fattening will not pose a risk to consumers, provided that maximum contents in nicarbazin of 0.1% p-nitroaniline (PNA) and 0.4% methyl(4-nitrophenyl) carbamate (M4NPC) would be respected. No withdrawal time is required. Residue data comply with the established maximum residue limits (MRLs). Nicarbazin is not a skin or eye irritant and not a skin sensitiser. These conclusions also apply to the additive Coxar®. Inhalation toxicity of nicarbazin is limited; the granulated additive has a low dusting potential. No risk for users is identified. Based on the available data, the FEEDAP Panel cannot conclude on the safety of Coxar® for the environment. The efficacy of 100 mg nicarbazin from Coxar®/kg feed was demonstrated in three anticoccidial sensitivity tests (AST), but only in one floor pen study. The floor pen study with 75 mg nicarbazin failed to demonstrate evidence of efficacy. No final conclusions on the efficacy of nicarbazin from Coxar® for turkeys for fattening can be drawn. [ABSTRACT FROM AUTHOR]