Coccidiostats are pharmacologically active molecules employed since 1940, to prevent and inhibit parasitic protozoa of the Phylum Apicomplexa and the genus Eimeria, referred to as coccidia, causing a very contagious disease of the gastrointestinal tract in many farmed animals. Decoquinate is the marker residue. Deccox, containing decoquinate as the active substance, is a feed additive intended to be used for the prevention of coccidiosis in chickens for fattening at a dose range of 20-40 mg/kg complete feed. Anticoccidial sensitivity tests (AST) could replace field trials provided they meet the criteria mentioned in the relevant guidance document on coccidiostats and histomonostats (EFSA FEEDAP Panel, 2011a).55. Journal of Veterinary Pharmacology & Therapeutics, 35, 41727. Experimental design of floor pen studies performed with Deccox. Diseases of Aquatic Organisms, 55, 1722. A rat developmental toxicity study showed fetotoxicity (retarded skeletal development) at 300 mg/kg bw per day, with a NOEL of 100mg/kg bw per day, but showed no embryotoxicity or teratogenicity. Toxicology Letters, 163, 213223. The stability of the additive (three batches) was investigated under longterm conditions (at 25C/60% relative humidity (RH)) up to 36months and under accelerated conditions (at 40C/75% RH up to 6months.15 After 36months at longterm conditions, decoquinate recovery rate was 107%, 100% and 100%, respectively, for the three batches. The resulting mixture should then be top dressed or . UK Supreme Court Asked to Block Oil Drilling at Horse Hill Field Decoquinate is a 4-hydroxy quinolone agent that has anticoccidial activity. in chickens for fattening. The acceptable daily intake (ADI) is 0.075mg decoquinate/kg bw per day applying an uncertainty factor of 200 to the NOEL. EFSA Journal 2010;8:1661. In 2014, the Panelissued an opinion on a new formulation (AviDeccox 60G) of the additive (EFSA FEEDAP Panel, 2014). The samples were incubated in the dark at 20C for up to 120days, under aerobic conditions. In trial 1, mortality data was statistically analysed by chisquare test, lesion scores by MannWhitney Utest and all other parameters by analysis of variance (ANOVA). Opinion of the Scientific Panelon Additives and Products or Substances Used in Animal Feed on a request from the Commission on the coccidiostat Deccox in accordance with article 9G of Council Directive 70524/EEC. Zhou Y, Luan M, Xu F, Gui G, Bu S, Wang B, Xia L, Li Y and Chen X, 2009. The FEEDAP Panelused the data provided by the applicant together with data from other sources, such as previous risk assessments by EFSA or other expert bodies, peerreviewed scientific papers, and other scientific reports, to deliver the present output. EFSA government site. No statistical analysis was performed on the mean values. Scientific opinion on the modification of authorisation of Deccox (decoquinate) as feed additive for chickens for fattening. It was evident from the outset that decoquinate, or its transformation products, adsorbed very strongly to each of the soils under investigation, as freely extractable radioactivity only accounted for up to 9% of that applied (ethanol was used as the extractant). The European Commission received a request from Pfizer Ltd.2 for reevaluation of the product Deccox (decoquinate), when used as a feed additive for chickens for fattening (category: coccidiostats and histomonostats). Body weight and feed consumption were measured on days 0, 21 and 35 on a pen basis. Affected horses can have focal or multifocal central nervous system (CNS) disease.EPM can be difficult to diagnose antemortem. . Very hydrophobic substances like decoquinate might sorb so strongly to soil that the degradation is hampered. The present study was conducted to . The .gov means its official. 19Technical dossier/Supplementary information April 2015/Annex 2_1. What is decoquinate used for? - TeachersCollegesj 11Technical dossier/SectionII/Annex II.1.5.2. Deccox 0.5% is used as an aid in the prevention of coccidiosis in ruminating and non-ruminating calves and cattle. Horses - Deccox was non-toxic to horses when fed at 12.5 times the recommended level for 14 days. The approach followed by the FEEDAP Panelto assess the safety and the efficacy of Deccox (decoquinate) is in line with the principles laid down in Regulation (EC) No429/2008 and the relevant guidance documents: Guidance for the preparation of dossiers for coccidiostats and histomonostats (EFSA FEEDAP Panel, 2011a), Technical guidance: Tolerance and efficacy studies in target animals (EFSA FEEDAP Panel, 2011b), Technical Guidance for assessing the safety of feed additives for the environment (EFSA, 2008a), Guidance for the preparation of dossiers for the reevaluation of certain additives already authorised under Directive 70/524/EEC (EFSA, 2008b), Guidance for establishing the safety of additives for the consumer (EFSA FEEDAP Panel, 2012a), Guidance on studies concerning the safety of use of the additive for users/workers (EFSA FEEDAP Panel, 2012b) and Technical Guidance: Microbial Studies (EFSA, 2008c). Scientific opinion on the safety and efficacy of the product Cylactin (Enterococcus faecium) as a feed additive for chickens for fattening. Deccox was considered not irritant to skin and eyes and has no sensitisation potential. The FEEDAP Panelnoted that the literature search on the toxicology profile of decoquinate did not reveal any new data relevant to consumer safety and reiterates its previous conclusions. The literature search provided by the applicant on the toxicology profile of decoquinate did not reveal any new data relevant to user safety (AppendixA).32. Decoquinate in horses acts on the sporozoite stage of the life cycle. No practically relevant interactions with other additives or . Efficacy of decoquinate against - ScienceDirect The final body weight of the uninfected groups and that of the infected groups were 2,215g and 2,036g respectively. The repeateddose oral toxicity studies and developmental studies reported were done to standards appropriate to the time but some were not in accordance either with GLP or with previous and current OECD guidelines. A Koc of 400,000 is used for the further risk assessment. The FEEDAP Panelreiterates its previous conclusions: For the present assessment, the applicant makes reference to the same studies assessed in the former EFSA FEEDAP opinions (EFSA, 2003 and EFSA FEEDAP Panel, 2013) and performed a literature search on the toxicology of decoquinate (AppendixA). Cumulative feed intake and final body weight were significantly higher in IT group than in IUC group. Deccox is safe for the consumer under the proposed conditions of use. There were no statistically significant differences between treatment groups in absolute organ weight for the bursa of Fabricius, heart, kidneys, liver or spleen; and in organ weights relative to body weight for the heart, kidneys and liver. Means in columns within a study with different superscript are significantly different (p0.05). and Trial 3: Technical dossier/SectionIV/Annex IV.2.6. Mass balance was demonstrated to be quantitative. Dangers: Poisonous if ingested and may be fatal. Offspring from the adult which died during the test were omitted from the calculation of total number of offspring and mean number of offspring per test animal. Levels of aflatoxin B1 were <1g/kg, aflatoxins B2, G1, G2 (one batch) <1g/kg. Toxicology Letters, 163, 21323. For the determination of decoquinate residues in tissues, the Applicant submitted a single laboratory validated and further verified method, based on reversedphase highperformance liquid chromatography coupled to a triple quadrupole mass spectrometer in electrospray ionisation mode (RPHPLCMS/MS) using matrix matched standards. Subsequent organic matter fractionation of these residues demonstrated that most of the radioactivity was associated with the humin fraction (up to 23%). The presence of blood in faeces was first observed in 8 pens of the IUC group 14days after inoculation followed by 7 and 9 pen observations 1 and 2days later, respectively. Crosscontamination of nontarget feedingstuffs by decoquinate authorised for use as a feed additive. No mortality or abnormal behaviour was observed. Safety and efficacy of Deccox (decoquinate) for chickens for fattening The effect of [14C]decoquinate on the reproductive capacity of D.magna was investigated following the OECD guideline 211 in a GLPcompliant study.50 The study was conducted over a 21day exposure period, under semistatic conditions with test solutions renewed three times per week. No significant differences in the OPG values were found on any of the observation days between the untreated and the treated groups and within the uninfected and the infected groups, respectively (Table8). The FEEDAP Panelnoted that during the test, clean manure was added to feed the worms. Significantly reduced OPGs by the treatment were found 16 and 21days after inoculation (Table8). Deccox is safe for the consumer under the proposed conditions of use. Decoquinate | VCA Canada Animal Hospitals Regulation (EC) No1831/20031 establishes the rules governing the Community authorisation of additives for use in animal nutrition. No maximum residue limits are considered necessary. No statistically significant differences were identified in any of the performance parameters evaluated (means: 1,969g body weight, 55g average daily gain, 1.50 feed to gain ratio, and 84g daily feed intake) between any of the dose levels tested or when compared to the control group. 50Technical dossier/Supplementary information September 2016/Annex 1. The EFSA Journal 2003;17:140. The mean values were at the same level for all four groups (Table10). A total of 240 onedayold chickens (Ross) was randomly distributed to 4 groups (6 replicates of 5 birds per sex) and fed cornsoybeantype diets supplemented with 0, 40 (1x maximum proposed dose), 200 (5x) and 400 (10x) mg decoquinate/kg for 35days.19 A starter diet (crumbles, calculated contents: 21.7% crude protein (CP), 12.8 MJ of metabolisable energy (ME)/kg) was given until day 21, followed by a grower diet (pellets, calculated contents: 20% CP, 13.0MJ ME/kg). Recovery rates after 12months under accelerated conditions were between 96% and 103%. No new study has been submitted by the applicant. In contrast to that, bloody faeces were found in the IT group only in 4 and 1 pens 14 and 16days after inoculation, respectively. Deccox, containing decoquinate as the active substance, is a feed additive intended to be used for the prevention of coccidiosis in chickens for fattening at a dose range of 2040mg/kg complete feed. Considering both studies the DT50 of decoquinate transformation in soil ranges between 96 and 140 days. EFSA Journal 2003; 17:140. No lesions were found for the uninfected groups 7 and 14 days after inoculation (Table11). The applicant made reference to the same studies assessed in a former EFSA FEEDAP opinion (EFSA, 2003) with the addition of new studies. At the end of the experiment, for some chickens (exact number not given) of the group with 150mg decoquinate/L water for drinking, mild clinically adverse reactions were reported (mental depression, decreased feed intake and dishevelled feathers) and necrosis in renal tubular epithelium and focal inflammatory cell infiltration in the liver. The recovery rates in feed samples appeared to be stable under longterm conditions with values of 111%, 106% and 111% after 3, 6 and 12weeks of storage. 12Technical dossier/Supplementary information April 2015/Annex 1.1. Scientific Opinion on the safety and efficacy of Deccox (decoquinate) for chickens for fattening. The acute toxicity of decoquinate to Daphniamagna, under semistatic conditions, was investigated following the OECD guideline 202.49 As decoquinate was shown not to be toxic in the range finding phase of the study, the definitive phase was conducted as a limit test. The low vapour pressure indicates that the substance will not volatilise to any great extent. The calculated bioaccumulation factor (BAF) was the highest at day 2 (BAF of 0.27 calculated on wet weight basis); after day 14, the BAF was lowered to 0.110.15 wet weight. 36Technical dossier/SectionIII/Annex III_4_1_Reference 7. The soils were incubated under aerobic conditions and maintained in the dark at about 50% maximum water holding capacity at 202C for up to 120days (recalculate at 12C). No significant differences were seen in haematology and clinical blood chemistry. Under both sets of conditions, the retention time for decoquinate was longer than that for the most strongly retained reference substance (DDT; log Koc=5.63) and as such, it was established that the log Koc value for decoquinate was >5.63 (Koc=426,580). 51Technical dossier/SectionIII/Annex III_4_1_Reference 25. Radioactivity recovered in organic soil extracts declined slightly as the incubation progressed, but was much improved compared with that observed in the first study, particularly in the early sampling intervals. For the risk assessment, the NOEC for decoquinate has been conservatively assigned as 16.3mg/kg (dry weight basis), thus providing a considerable margin of safety. Other anticoccidial additives were tested (five in ASTs 1 and 3, six in AST 2) and the statistical analysis referred to all groups. Is decoquinate harmful to dogs? - Studybuff In terms of comparative metabolism, it appeared that the absorbed fraction of decoquinate is metabolised more extensively in rat than in chicken, with the production of different metabolites. the contents by NLM or the National Institutes of Health. 52Technical dossier/SectionIII/Annex III_4_1_Reference 26. The ratios predicted environmental concentration/predicted no effect concentration (PEC/PNEC) for terrestrial, aquatic compartment and sediment are below 1, indicating that decoquinate used in chickens for fattening up to the highest proposed dose, does not pose a risk for these compartments; as well, no risk is expected neither for secondary poisoning nor for groundwater contamination. The residue data submitted confirm that no MRLs are considered necessary.. The three floor pens studies could not convincingly demonstrate the efficacy of decoquinate whereas the three anticoccidial sensitivity tests did. An overview of the toxicological profile of decoquinate firstly assessed by the FEEDAP Panelin 2003 (EFSA, 2003) and then updated in 2013 (EFSA FEEDAP Panel, 2013) is given below. A mass balance was determined for each sample. Decoquinate is not genotoxic and not carcinogenic. No significant differences were found at the following examination days. Federal government websites often end in .gov or .mil. EFSA (European Food Safety Authority), 2009. Decoquinate (ethyl6decyloxy7ethoxy4hydroxyquinoline3carboxylate, C24H35NO5, molecular weight 417.6g/mol, Chemical Abstracts Service No 18507896), is a synthetic compound of the quinoline family. EFSA FEEDAP Panel The product Deccox containing 60g/kg decoquinate as active substance is a feed additive intended to be used in chickens for fattening for the control of coccidiosis caused by Eimeria spp. 59AST 1: German field isolate (2008); estimated dosage per bird: 251,105 sporulated oocysts (225,550 E.acervulina, 25,555); AST 2: Poland field isolate (2010); estimated dose per bird: 271,100 E.acervulina sporulated oocysts; and AST 3: Belgium field isolate (2010); estimated dose per bird was 273,100 sporulated oocysts (245,000 E.acervulina, 2,500 E.maxima, 25,600 E.tenella). Decoquinate is a chemically synthesized 4-hydroxyquinolone anti-protozoan agent. Daphnids were exposed over a 48h exposure period, under semistatic conditions (24h replacements). Decoquinate Combined with Levamisole Reduce the Clinical - ResearchGate The sporozoite apparently can still penetrate the host intestinal cell, but further development is prevented. Scientific opinion of the Panelon Plant Protection Products and their Residues on a request from EFSA related to the default Q10 value used to describe the temperature effect on transformation rates of pesticides in soil. The toxicity of decoquinate to chironomids was investigated in a GLPcompliant study, using sediment which had been fortified with [14C]decoquinate.52 The test design was based on draft guidance which was available at the time study was initiated.53 The FEEDAP Panelnoted that some minor differences exist between this study and the current OECD guideline 233 on spiked sediment toxicity test design, but these are not considered to have an impact on the results obtained from this study. Combined sample extracts were submitted for chromatographic analysis using HPLC. Adult earthworms were removed from test soil and assessed for mortality, weight change and sublethal effects after 28days of exposure. AST 2: Annex IV.2.2. 25The United States FDA had recorded the incompatibility with bentonite used as a binder in pelleting. The IC 50 of decoquinate was 0.5 0.09 nM for the Sn6 isolate of S. neurona from a horse and 1.1 0.6 nM for the SnOP15 isolate of S. neurona from an opossum. In trial 1, decoquinate at 20mg/kg feed reduced significantly coccidiosisrelated mortality. A combination product containing decoquinate and levamisole has been shown to reduce clinical signs of EPM in treated horses (Ellison and Lindsay, 2012). A concurrent increase in nonextractable residues was evident, accounting for means of 15% and 30% at day 120 in loamy sand and clay loam, respectively. (European Food Safety Authority), 2008b, revised in 2009. No data were provided on the fate of decoquinate in manure. The stability of decoquinate (one batch) was studied in a vitaminmineral premixture (without choline chloride, intended concentration 4,000mg decoquinate/kg premixture)17 and in complete feed (maize, soybean, pea type; intended concentration 20mg decoquinate/kg feed)18 for chickens for fattening. Feed intake and body weight of the animals were measured throughout the study, feed to gain ratio was calculated. The results of the new study correlate well with the old study and show that decoquinate is partly transformed to a number of degradation products, which are not mineralised in soil. EPM still poses diagnostic challenges and can be difficult to differentiate from other neurological diseases. Li Q, Xie LH, Caridha D, etal, 2014. Earthworms were exposed to decoquinate in artificial soil over a 28day exposure period, at nominal concentrations equivalent to 62.5, 125, 250, 500 and 1,000mg/kg dry soil. No precipitation of [14C]decoquinate was observed in any of the test vessels during the study. Acknowledgements: The EFSA FEEDAP Panel(EFSA Panelon Additives and Products or Substances used in Animal Feed) wishes to thank the following for the support provided to this scientific output: Jaume Galobart, Gloria LpezGlvez and Paola Manini. It may also be effective in treating or preventing hepatozoonosis or sarcocystosis myositis. Iglesias A, Nebot C, Miranda JM, Vzquez BI, Cepeda A, 2012. The lack of significant adult immobilisation or reduction in offspring production indicated that exposure to [14C]decoquinate over a 21day period had no effect on D.magna survival and reproduction at any of the tested concentrations. Instead, the Koc determination was undertaken for decoquinate in accordance with the screening method OECD guideline 121, in compliance with GLP.36 The log Koc of decoquinate was estimated by comparing its retention time, using two different mobile phases, to that of a range of substances for which log Koc values have been determined. Analysis of test samples from the definitive test in freshly prepared solutions and on days 3, 5, 7, 10, 12, 14, 17, 19 and 21 in expired solutions indicated that concentrations of [14C]decoquinate were not maintained within 20% of the initial measured values. No practically relevant interactions with other additives or veterinary drug exist except with bentonite. Bertelsen U, Dorne JL CM, FernandezCruz ML, etal, 2008. Sheep - decoquinate was found safe for sheep at 4 g/kg/bwin a single oral dose. No adverse effects were seen in rats at doses of up to 37.7mg/kg bw per day for up to 2years. No practically relevant interactions with other additives or veterinary drugs exist except with bentonite. (European Medicines Agency Committee for Medicinal Products for Veterinary Use), 2000. Pairwise treatment comparisons were made if the general analysis indicated significance. Decoquinate was shown to be a substance of low toxicity, the most severe findings being . The lowest NOEL was 15mg/kg bw per day, observed in a 12week oral toxicity study in dogs. 48Technical dossier/SectionIII/Annex III_4_1_Reference 23. The previous studies, the new studies and the outcome of a literature search performed by the applicant covering the period 2004201433 were assessed by the FEEDAP Panelfollowing Regulation (EC) No429/200834 and the FEEDAP technical guidance for assessing the safety of feed additives for the environment (EFSA, 2008a). 35Technical dossier/SectionIII/Annex III_4_1_Reference 17. Levamisole is commercially available as a dewormer for cattle, sheep, goats, and pigs. The groups with 15, 45 and 75mg decoquinate/L water for drinking showed a significant improvement of body weight gain at 21day body weight gain (average about 361g) and feed to gain ratio (average about 2.53) compared to the groups with 0 and 150mg (average about 262g and 3.33, respectively). Coefficient of variation of measured concentrations of decoquinate in the series of samples did not exceed 15% at any sampling day. The number and sex of emerged adult chironomids were recorded daily during the exposure period. Guidance for the preparation of dossiers for coccidiostats and histomonostats. Capleton AC, Courage C, Rumsby P, Holmes P, Stutt E, Boxall AB, Levy LS, 2006. PDF Equine Protozoal Myeloencephalitis: Investigating Immunopathogenesis Considering the frequency of the single lesion scores, the only significant difference in favour of the treatment was found for lesion score 3 in the caecum on both observation days. Test solutions were replaced after 24h. The test solutions appeared opaque and offwhite colour with small quantities at the surface. EFSA The history of decoquinate in the control of coccidial infections in ruminants. EFSA Journal 2009;7:112. Feed to gain ratios were not significantly influenced by the treatment. EFSA FEEDAP Panel The supplemented feed used in the tolerance study contained 39, 203 and 389mg decoquinate/kg starter diet and 50, 280 and 596mg decoquinate/kg grower feed (for 40, 200 and 400mg intended decoquinate/kg complete feed, respectively). Equine protozoal myeloencephalitis (EPM) remains an important neurologic disease of horses.There are no pathognomonic clinical signs for the disease. [14C]Decoquinate levels declined as the incubation progressed, accounting for 52% and 53% at day 120 in loamy sand and clay loam, respectively. 43Technical dossier/SectionIII/Annex III_4_1_Reference 21. consists of 6% decoquinate, 0.6% colloidal silica, 2.85% soyabean oil on a wheat middlings carrier. 24Total protein, albumin, globulin, AST, ALT, LDH, ALP, glucose, BUN, creatinine, calcium, phosphorus, sodium, potassium and chloride. Capleton AC, Courage C, Rumsby P, etal, 2006. Infection resulted in an increase of mortality (15.3%) without a positive effect of the treatment. The analytical data from five batches of the active substance confirmed compliance with the specifications: 98.799.6% decoquinate, 0.080.11% 6decyloxy7ethoxy4hydroxyquinoline3carboxylic acid, Decoquinate - an overview | ScienceDirect Topics (EFSA Panelon Additives and Products or Substances used in Animal Feed), 2011a. Safety and efficacy of Deccox (decoquinate) for chickens for fattening EFSA (European Food Safety Authority), 2003. The applicant made a literature search for interactions of decoquinate with other additives and veterinary drugs (AppendixA).26 Since no new findings were reported, the FEEDAP Panelmaintains its former conclusion that no incompatibilities or interactions with feedingstuffs, carriers, other approved additives or medicinal drugs are expected with the exception of bentonite. Performance data and mortality of chickens in floor pen trials with Deccox. 49Technical dossier/SectionIII/Annex III_4_1_Reference 22. Guidance on studies concerning the safety of use of the additive for users/workers. Decoquinate - NexGen Pharmaceuticals Decoquinate (brand name: Deccox) is an antiparasitic medication used to prevent coccidia infections in dogs. 28Databases searched: PubMed; time span: up to 2014. and transmitted securely. The DT50 values for decoquinate transformation were estimated to be 96, 116 and 140days. Mercier P, MorelSives A, Verdelhan S, etal, 2005. However, the quality of the studies was considered sufficient for the assessment. 29Technical dossier/Supplemetary information April 2015/Annex 5_III. 8600 Rockville Pike is a buffcoloured coarse powder formulation to be incorporated in feedingstuffs through premixtures. Repeat dose studies of orally administered decoquinate have been carried out in rats and dogs. The data indicate that the fivefold overdose of decoquinate is tolerated by chickens for fattening. The only positive effect of decoquinate seen in the third study (trial 3) consists of a decrease in the severity of intestinal lesions with time. Its use in dogs to prevent certain parasitic infections is 'off label' or 'extra label'. A saturated solution was prepared by ultrasonication of excess decoquinate in daphnid medium (nominally 100mg/L), prior to the addition of the test organisms. PDF Decoquinate Combined with Levamisole Reduce the Clinical Signs and Deccox No biologically relevant treatment effects were identified during the course of this study. In each soil type, low levels of 14CO2 (up to 2% of applied radioactivity) were released over the course of the incubation period, indicating that decoquinate or its degradation products were not mineralised38 to a significant extent. Dr. Ellison owns Pathogenes and sells levamisole alone or in combination with decoquinate as treatment for equine protozoal myeloencephalitis. Three floor pen studies in chickens for fattening were submitted.56 Birds were penned and distributed into treatment groups as indicated in Table6.57 Treated groups received feed containing 20mg decoquinate/kg feed; dosage was analytically confirmed. The ratios predicted environmental concentration/predicted no effect concentration (PEC/PNEC) for terrestrial, aquatic compartment and sediment are below 1, indicating that decoquinate used in chickens for fattening up to the highest proposed dose, does not pose a risk for these compartments; as well, no risk is expected neither for secondary poisoning nor for groundwater contamination.
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