Nicarbazin Complex Yields Dinitrocarbanilide as Ultrafine Crystals with Improved Anticoccidial Activity

Ef, Rogers; Brown, RD; Brown, J. E.; Kazazis, DM; Leanza, W. J.; Nichols,; Ostlind, D. A.; Rodino, TM

doi:10.1126/science.6635662

Cited by 29 publications

(20 citation statements)

References 13 publications

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“…When NCZ is ingested, it dissociates into its constituent parts, DNC and HDP. Once dissociated, however, DNC aggregates to form large particles that inhibit absorption through the intestinal wall (Rogers et al 1983;Bynum et al 2005;Yoder et al 2006c). So if conditions in the pigeon gut promote aggregation of DNC, then it could require greater exposure to NCZ to achieve the same level of effectiveness as in other birds.…”

Section: Discussionmentioning

confidence: 99%

Nicarbazin bait reduces reproduction by pigeons (Columba livia)

Avery¹,

Keacher²,

Tillman³

2008

Wildl. Res.

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Abstract. Development of effective methods for reducing populations of overabundant nuisance bird species continues to challenge wildlife biologists. Reproductive inhibition, although conceptually pleasing, has been difficult to implement because of the lack of a safe, approved avian contraceptive. Recently, however, nicarbazin received regulatory approval in the United States for use as a bait to decrease hatchability of resident Canada goose (Branta canadensis) and feral pigeon (Columba livia) eggs. In anticipation of the feral pigeon registration, we evaluated efficacy by exposing captive pairs of nesting pigeons to nicarbazin bait for 4 h daily. Egg production was unaffected, but only 9 of 22 eggs hatched, a 59% reduction from pre-treatment when each of the 11 test pairs produced 2 nestlings. In the recovery phase, when treated bait was removed, the 11 pairs produced 18 nestlings. All nestlings produced during the study appeared healthy and normal, and there was no mortality among the adult pairs. Nicarbazin is an effective and safe means of reducing hatchability of feral pigeon eggs that can be used within an integrated management plan to reduce feral pigeon populations.

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Section: Discussionmentioning

confidence: 99%

Nicarbazin bait reduces reproduction by pigeons (Columba livia)

Avery¹,

Keacher²,

Tillman³

2008

Wildl. Res.

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“…The potency of DNC is increased ten fold when this molecule is complexed with HDP as nicarbazin, but no increase in anticoccidial activity is observed with a simple mixture of the two compounds (Cuckler et al, 1955). Rogers et al (1983) indicated that dissolution of the DNC-HDP complex in the gut results in the formation of much smaller DNC crystal size than if the water insoluble DNC is administered alone that would explain an increased efficacy. According to Porter and Gilfillan (1955), nicarbazin is at least partially broken down in the gut to DNC and HDP which may be absorbed independently.…”

Section: Product Descriptionmentioning

confidence: 99%

Opinion of the Scientific Panel on additives and products or substances used in animal feed (FEEDAP) on the efficacy and safety of the coccidiostat Koffogran

2004

EFSA Journal

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SUMMARYKoffogran is a feed additive intended for control of coccidiosis, a debilitating protozoal infection in poultry. In common with a number of other coccidiostats, Koffogran is due for evaluation to comply with statutory requirements agreed at an EU-level. The European Commission asked the EFSA to evaluate the product and advise the Commission on its efficacy and safety. Within EFSA this task was allocated to the Scientific Panel on Additives and Products or Substances used in Animal Feed (FEEDAP Panel). The data provided in the dossier proved insufficient to give conclusive answers to the several questions raised by the European Commission.Koffogran contains 25 % nicarbazin as the active substance. Nicarbazin is a complex of the components 4,4'-dinitrocarbanilide (DNC) and 2-hydroxy-4,6 dimethylpyrimidine (HDP). It is effective as anticoccidial in chickens for fattening up to a maximum age of four weeks at a level of 100 to 125 mg nicarbazin kg -1 complete feed. However, a full assessment of the present day efficacy was not possible as an insufficient number of up-to-date trials had been carried out.Tolerance tests showed that Koffogran is safe for the chickens with a small, but acceptable margin of safety. Incompatibilities or interactions with feedingstuffs, carriers, other approved additives or medicinal drugs are not to be expected based on the known history of the additive.At feed level concentration nicarbazin had no activity against a range of pathogenic and non-pathogenic bacteria. Nicarbazin had no effect on the colonisation or excretion of Salmonella enteritidis. Therefore, nicarbazin can be considered to be safe as far as microbiological risk is concerned.Nicarbazin is absorbed to a large extent by chickens. The metabolic fate of nicarbazin shows that the DNC and HDP components of the complex are split and behave independently, the DNC moiety being mainly excreted in the faeces while the HDP mainly appears in the urine. The DNC metabolic fate has been established and the main metabolites identified in the excreta and tissues. DNC can be considered as the marker residue, but non identified metabolites represent more than 50 % of the total residues in the kidney and liver beyond a 3-day withdrawal period. Even if the metabolic fate of the HDP moiety of nicarbazin has not been investigated in depth, it appears that HDP is metabolised to a very limited extent and that the consumer is mainly exposed to HDP and not to its potential metabolites. The liver is the target tissue. Although the kinetics of HDP residues (or eventually the whole HDPderived compounds) are not available. Opinion on the additive Koffogran 2/40The submitted toxicological studies did not indicate a significant potential for target tissue toxicity, such as neurotoxicity, immunotoxicity, impaired fertility in mammals or endocrinemediated effects. The compound is unlikely to pose a carcinogenic risk. However, the toxicological dossier is far from satisfactory according to the present scientific standards. For developmental toxicity, e...

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“…A high‐performance liquid chromatography (HPLC) method was developed to assay nicarbazin levels in the egg shell by measuring DNC 4. DNC is the active component of the mixture that comprises the nicarbazin formulation; HDP is thought to facilitate uptake of DNC in the gut 5. For each treatment group, DNC concentrations in the shells were correlated with the concentration of DNC determined for the egg contents (yolk and albumin, combined) 6.…”

Section: Introductionmentioning

confidence: 99%

4,4′‐Dinitrocarbanilide (DNC) concentrations in egg shells as a predictor of nicarbazin consumption and DNC dose in goose eggs

Stahl¹,

VerCauteren²,

Köhler³

et al. 2003

Pest Management Science

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Nicarbazin is being investigated as an infertility agent for the control of non-migratory Canada geese (Branta canadensis L) populations. Nicarbazin is presently registered for use as a coccidiostat for poultry. Geese fed sufficient quantities of nicarbazin will lay non-viable eggs. We established nicarbazin consumption by measuring the concentration of a component of the formulation, 4,4'-dinitrocarbanilide (DNC) in the egg contents (yolk, albumin) in non-viable eggs. To estimate the nicarbazin consumption of birds that laid viable eggs (eggs that hatched or contained an embryo), a high-performance liquid chromatography method was developed to measure the concentration of DNC in egg shells. A statistically significant correlation was established using linear regression between the mean concentrations of DNC in the egg shell and in the egg contents in non-viable eggs. Viable eggs were estimated to contain lower levels of DNC than non-viable eggs. DNC concentrations in both the egg contents and the egg shell increased with increases in nicarbazin dose in feed. Our method allows for the estimation of nicarbazin consumption and DNC dose in eggs under field conditions, which is important in developing an effective infertility agent for over-abundant non-migratory goose populations.

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Nicarbazin Complex Yields Dinitrocarbanilide as Ultrafine Crystals with Improved Anticoccidial Activity

Cited by 29 publications

References 13 publications

Nicarbazin bait reduces reproduction by pigeons (Columba livia)

Nicarbazin bait reduces reproduction by pigeons (Columba livia)

Opinion of the Scientific Panel on additives and products or substances used in animal feed (FEEDAP) on the efficacy and safety of the coccidiostat Koffogran

4,4′‐Dinitrocarbanilide (DNC) concentrations in egg shells as a predictor of nicarbazin consumption and DNC dose in goose eggs

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