Nicarbazin

An experiment was conducted with young battery-reared chickens to evaluate the effects of graded levels of nicarbazin (0, 40, 80, 120, and 160 ppm) on plasma pigmentation in the presence and absence of coccidial infection. A second experiment was also performed to determine whether nicarbazin (50 ppm) and the narasin nicarbazin combination anticoccidial (50 ppm each) affected pigmentation values in coccidia-infected and healthy chicks. Pigmentation values were expressed as micrograms beta-carotenoid equivalents per milliliter of plasma (beta-CE). Results of these studies indicated that nicarbazin improved beta-CE in both parasitized and coccidia-free chicks, but the magnitude of improvement was greater in coccidia-infected animals. Linear responses to nicarbazin additions were observed in both groups. The second experiment revealed that the effects produced in healthy chicks receiving the narasin nicarbazin combination were equivalent to those which received nicarbazin alone, indicating that the nicarbazin response in beta-CE is manifested with the combination anticoccidial as well.

Four floor pen studies were carried out to evaluate the effects of nicarbazin (NIC) administration on blood glucose concentrations and the onset of hypoglycemia in broiler chickens. All tests involved continuous NIC feeding at 0, 100, or 125 ppm to 28 days of age. In each study, birds were reared at both standard environmental temperatures and at 3 C below this level. In addition, two studies were conducted in the presence of coccidial infection and two were carried out in noninfected broilers. At 26 days of age in each test, two birds per pen were bled by puncture of the brachial vein, and whole blood glucose concentrations were determined. Results indicated that the administration of NIC to broilers for 26 days had no effect on blood glucose concentrations, although graded levels of NIC tended to increase these values. In addition, no evidence of hypoglycemia was recorded in any of the trials. In a similar fashion, blood glucose was unaffected by environmental temperature and coccidial challenge. These findings support previous work showing that NIC administration does not influence blood glucose levels and indicate that the product is not involved when field diagnoses use reduced blood glucose and hypoglycemia as indicators of production anomalies.

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.

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 the accidental feeding of a compound feed containing the coccidiostat nicarbacin in layer breeder flocks (Lohmann Brown Classic), the birds displayed distinct clinical signs within a few hours. Mortality increased during the following 5 days, whereas laying performance and hatching rate of eggs during this period decreased markedly. Egg shell discoloration was observed as early as during the first day. As a consequence, an association between feeding of the coccidiostat nicarbacin and the observed symptoms was assumed. Recent studies indicate that Nicarbacin reduces the activity of aminolevulinic acid synthase type 1 (ALAS 1), which is responsible for the synthesis of protoporphyrin IX in the shell gland as main compound of brown egg shells. Reduced laying performance and increased mortality was likely due to nicarbacin-induced deregulated body temperature homeostasis and concomitant imbalances in acid-base status of the animals. The case reveals that the accidental feeding of nicarbacin to non-target animals such as laying hens and their parents may result in acute clinical symptoms. This highlights the necessity of appropriate care in handling feed additives and their premixes for specific non-target animals and should sensitize farmers and veterinarians.

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.

A clinical study was made into the abilities of nicarbazin and monensin and a nicarbazin + monensin combination to controlEimeria acervulina,E. maxima, andE. tenellain 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 ofE. acervulinaandE. maximabut was able to suppress lesions caused byE. tenella. Nicarbazin 40 ppm + monensin 40 ppm suppressed lesions of all three species.RESEARCH HIGHLIGHTSNicarbazin or monensin at 40 ppm gave only partial control ofEimeriaspp. A combination of 40 ppm nicarbazin + 40 ppm monensin controlled DWG, DFI and FCR. Nicarbazin or monensin at 40 ppm did not suppress allEimeriaspp. lesions. Nicarbazin 40 ppm + monensin 40 ppm suppressed lesions of all three species.

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.

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.