Coccidiosis is a parasitic disease affecting a variety of animals, especially mammals and birds. Most of the radioactivity administered was recovered in the faeces (8287%), urine being a minor excretion route (0.20.4%). Sarcocystis neurona is a protozoan apicomplexan parasite that causes the neurological disease equine protozoal myeloencephalitis (EPM) in horses residing in the Americas. 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. 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. The history of decoquinate in the control of coccidial infections in ruminants. 45Technical dossier/SectionIII/Annex III_4_1_Reference 18. EFSA (European Food Safety Authority), 2009. 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. . In 2014, the Panelissued an opinion on a new formulation (AviDeccox 60G) of the additive (EFSA FEEDAP Panel, 2014). 2On 27/09/2013 the applicant informed EFSA that the petitioner changed from Pfizer Ltd. to Zoetis Belgium SA, Rue Laid Burniat 1, 1348 LouvainlaNeuve, Belgium. 13Technical dossier/Supplementary information April 2015/Annex 1.5. The methodology for the calculation of the maximum PEC soil, groundwater and surface water are described in the technical guidance for assessing the safety of feed additives for the environment (EFSA, 2008a). 40The temperature correction was performed according to the 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 (EFSA, 2007). (European Medicines Agency Committee for Medicinal Products for Veterinary Use), 2000. The degradation of [14C]decoquinate was investigated in two GLPcompliant studies. 2000 Decoquinate Summary Report (2). Zhou Y, Yi M, Xu F, etal, 2009. Owing to the absence of findings by macroscopy, no histology was performed. No treatmentrelated adverse effects were seen in any of the studies at doses of 15mg/kg bw per day or less and this dose was therefore adopted as the overall NOEL. Question No EFSAQ2005220H, EFSA Journal 2008;656:126. (EFSA Panelon Additives and Products or Substances used in Animal Feed), 2012b. Scientific Opinion on the modification of the terms of authorisation of AviDeccox. EFSA issued an opinion on the safety and efficacy of Deccox in accordance with Article 9G of Council Directive 70/524/EEC (EFSA, 2003).5 In 2013, the EFSA FEEDAP Panelissued an opinion on the modification of the authorisation of Deccox for chickens for fattening (EFSA FEEDAP Panel, 2013) concerning the reduction of the withdrawal time from 3 days to zero days and the introduction of MRLs in edible tissues of chickens for fattening. 49Technical dossier/SectionIII/Annex III_4_1_Reference 22. The EFSA Journal 2003;17:140. In loamy sand, 101% of applied radioactivity was extracted at day 0, decreasing to 78% at day 120 and in clay loam, 102% of applied radioactivity was extracted at day 0, decreasing to 65% at day 120. 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.Decoquinate from Deccox is safe for chickens for fattening at the highest applied concentration in complete feed of 40 mg/kg. Feed intake and body weight of the animals were measured throughout the study, feed to gain ratio was calculated. 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. Decoquinate is of low acute toxicity by the oral route in a range of avian and mammalian species. Tissue metabolic profiles showed that decoquinate was the major component in liver, kidney, muscle, skin and fat (accounting for 19.6% of liver and kidney radioactivity and 23.9% of muscle, 31.2% of skin and 76.5% of fat total radioactivity). 17,18 These agents are used to treat intensively reared species inclu. In the absence of new data, the FEEDAP Panelconfirms its previous conclusions on the safety of decoquinate for the consumer. Diseases of Aquatic Organisms, 55, 1722. Effect of Dietary Antimicrobials on Immune Status in Broiler Chickens, AsianAustralian Journal of Animal Science. Scientific opinion of the panel on plant protection products and their residues (PPRPanel). 35Technical dossier/SectionIII/Annex III_4_1_Reference 17. EFSA The Eimeria field strains should ideally undergo one, but in any case not more than two passage(s) before use in such trials. 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. Vet Print Deccox This page contains information on Deccox for veterinary use. AST 2: Annex IV.2.2. Boxall AB, Fogg LA, Kay P, Blackwell PA, Pemberton EJ, Croxford A, 2003. (EFSA Panelon Additives and Products or Substances used in Animal Feed), 2013. People also ask What is levamisole used for in horses? Deccox was considered not irritant to skin and eyes and has no sensitisation potential. In trial 1, decoquinate at 20mg/kg feed reduced significantly coccidiosisrelated mortality. Samples of excreta were analysed for oocyst excretion and intestinal lesions were scored on five animals per pen following the method of Johnson and Reid (1970) (0=no lesion, 1=very mild, 2=mild, 3=moderate and 4=severe). The same studies are submitted for the current assessment.30. Dorne JL, FernandezCruz ML, Bertelsen U, etal, 2013. In a former opinion on Deccox (EFSA, 2003), two inhalation toxicity studies in rats were assessed: the studies were performed with the active substance (nose only) and did not show signs of irritation up to the highest concentration in air (4g/m3) after a 46h exposure. Based on the performance characteristics presented, the EURL recommends for official control the RPHPLCMS/MS method proposed by the Applicant to enforce the decoquinate MRLs in the relevant tissues. Due to insufficient evidence, the potential of decoquinate to prevent coccidiosis in chickens for fattening cannot be established. The inhalation risk for user is considered negligible since inhalation toxicity and exposure are very low. Bovatec and Rumensin are both ionophores, a class of antibiotics that are not used in human medicine. A Koc value of 400,000L/kg is considered an appropriate reference value for exposure calculation. For the present assessment, the applicant makes reference to the same studies assessed in the former EFSA FEEDAP opinions (EFSA, 2003; EFSA FEEDAP Panel, 2013). Deccox 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. The Panelnotes that the microbial contamination in some batches is high. For a highly persistent compound like decoquinate, a refined PEC in soil should be used according to the guidance, giving a PECplateau in soil, groundwater, surface water and sediment (Table2). Is decoquinate harmful to horses? Toxicology & Applied Pharmacology, 270, 196208. EFSA FEEDAP Panel (European Food Safety Authority), 2007. 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. Detection of veterinary drug residues in surface waters collected nearby farming areas in Galicia, North of Spain. The Phase I PEC trigger value for soil is exceeded. The seeds of hairy vetch when eaten in quantity by cattle and horses cause . Significantly reduced OPGs by the treatment were found 16 and 21days after inoculation (Table8). Since an assessment of the anticoccidial potential of an active substance has to be based on the positive outcome of three studies of each study type, the potential of decoquinate to prevent coccidiosis in chickens for fattening at the lowest applied dose of 20mg/kg complete feed cannot be established. Decoquinate is the marker residue. The technical dossier was prepared following the provisions of Article 7 of Regulation (EC) No1831/2003, Regulation (EC) No429/20087 and the applicable EFSA guidance documents. No information is available on the hydrolysis or biodegradation of decoquinate in water. The effect of decoquinate on terrestrial plants was investigated in a GLPcompliant study;41 the study followed the OECD guideline 208 which was in force at the time the study was conducted. Feed to gain ratios were not significantly influenced by the treatment. 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. EFSA (EFSA Panelon Additives and Products or Substances used in Animal Feed), 2011b. 16Technical dossier/SectionII/Annex II.4.1.1.2. Deccox is safe for the consumer under the proposed conditions of use. Two further minor unidentified components were also detected (up to 5% of applied radioactivity). Among the three floor pen trials submitted, only one (trial 1) provides evidence of the anticoccidial efficacy of 20 mg decoquinate/kg feed based on endpoints relevant for coccidiostatic efficacy; however, the study design and reporting showed some weaknesses. EFSA Journal 2003, 17:140. A preliminary range finding phase was conducted with nonradiolabelled decoquinate and no effects were evident at the highest sediment concentration which was tested (1,000mg/kg dry weight). Cho S, Fossler CP, DiezGonzalez F, Wells SJ, Hedberg CW, etal, 2013. The margin of safety is between 5 and 10. 12Technical dossier/Supplementary information April 2015/Annex 1.1. Based on a tolerance study and supported by a published safety study, the FEEDAP Panelconcludes that decoquinate from Deccox is safe for chickens for fattening at the highest applied concentration in complete feed of 40mg/kg. In particular, Article 10(2) of that Regulation also specifies that for existing products within the meaning of Article 10(1), an application shall be submitted in accordance with Article 7, at the latest one year before the expiry date of the authorisation given pursuant to Directive 70/524/EEC for additives with a limited authorisation period, and within a maximum of seven years after the entry into force of this Regulation for additives authorised without a time limit or pursuant to Directive 82/471/EEC. Zootechnical parameters (average daily weight gain, and feed to gain ratio) were calculated. For the terrestrial compartment, data are available for microorganisms, earthworms and plants. The number and sex of emerged adult chironomids were recorded daily during the exposure period. Decoquinate may afford a treatment option for Sarcocystis neurona in horses based on in vitro data in a patent submitted in 2001. xix This publication reported that SnSAG 1 and SnSAG 5 phenotypes required ten times more triazine drugs than decoquinate to kill the protozoa when tested in vitro. Coccidiosis, an intestinal plasmodium infection, is a major infectious disease in poultry and rabbits. 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. Toxicology Letters, 163, 213223. Pathogenes performed the IL-6 ELISA. In trial 2, mortality/culls did not differ significantly among groups (overall mean 4.3%). 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. [14C]Decoquinate levels declined as the incubation progressed, accounting for 52% and 53% at day 120 in loamy sand and clay loam, respectively. 8600 Rockville Pike 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. Addition- EFSA FEEDAP Panel Decoquinate is not genotoxic and is not carcinogenic. Journal of Veterinary Pharmacology and Therapeutics, 35, 41727. 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. 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). Depending on feed intake level, use 1.67 or 3.34 kg per metric tonne of complete feed to result in a daily dose level of 0.5 mg of decoquinate per kg body weight. The lesion score scale ranging from 0 to 4 was applied (Johnson and Reid, 1970). Scientific opinion on the safety and efficacy of Bacillus subtilis PB6 (Bacillus subtilis) as a feed additive for chickens for fattening, EFSA Journal 2009,7(9):1314. The LC50 for emergence and the EC50 for growth were higher than the highest concentration tested (100mg/kg dry weight soil) for each of the species evaluated. Data on impurities were provided for three batches of the additive.10 Results showed concentrations of arsenic between <0.020 and <0.040mg/kg, cadmium between 0.059 and 0.108mg/kg, lead between 0.07 and 0.13mg/kg and mercury below0.005mg/kg. The anticoccidial sensitivity tests demonstrated the efficacy of 30mg decoquinate/kg feed by an improvement of all endpoints related to this kind of test. Environmental Science and Pollution Research, 19, 32353249. When the DT50 of 140 days is adjusted to an incubation temperature of 12C using the Arrhenius equation,40 the new DT50 is about 300 days, which will be used for further calculations. EFSA FEEDAP Panel OECD guideline 121 may provide unreliable Koc values especially when log Koc>5.63; nevertheless, the study highlight the very high adsorption characteristics of the substance. EPM and Horses: 9 Fast Facts March 30, 2017 By Kentucky Equine Research Staff Equine protozoal myeloencephalitis (EPM) continues to plague horses, causing neurological deficits that threaten athletic careers and lives. The Committee for Medicinal Products for Veterinary Use (CVMP) of the European Medicines Agency (EMA) acknowledged in 2000 (EMEA CVMP, 2000) that decoquinate does not have antibacterial action. Guidance on studies concerning the safety of use of the additive for users/workers. Three ASTs were submitted.58 The three tests followed a similar design. Risk characterisation (PEC/PNEC ratio) of decoquinate for sediment. 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). Federal government websites often end in .gov or .mil. For each soil, duplicate samples were taken for analysis at 0, 14, 28, 42, 56, 70, 91 and 120days after treatment. The FEEDAP Panelconcluded in 2003 (EFSA, 2003) on a different database that decoquinate does not have marked antibacterial properties. EFSA After 72h, no significant effect on growth rate could be estimated leading to the conclusion that the NOEC is equal to the highest obtained soluble concentration of decoquinate in the test (0.234mg/L). The FEEDAP Panelnotes that in a more recent FDA publication (eCFR of March 23, 2017 558.195 Decoquinate as (d) Special considerations) it is indicated that Bentonite should not be used in decoquinate feeds (FDA (Federal Register on 12/27/2016) uses this warning for decoquinate, robenidine and carbadox). Total impurities are specified to be <2%. . A mouse lymphoma assay found that decoquinate caused gene mutation invitro at the highest concentration tested in the presence of metabolic activation, but it was questionable whether it should be regarded as a positive result as most of the cells were killed at this concentration. It may also be effective in treating or preventing hepatozoonosis or sarcocystosis myositis. Feed to gain ratio showed relations similar to those seen for body weight (Table12). Ionophores have many potential benefits besides prevention of coccidiosis, but they (especially Rumensin) can be toxic to equines and mixing errors have caused toxicity in ruminants. Decoquinate is a 4-hydroxyquinolone (ethyl-6-decyloxy-7-ethoxy-4-hydroxyquinoline-3-carboxylate) used for the prevention of coccidiosis in broiler chickens caused by E. tenella, E. necatrix, E. acervulina, E. mivati, E. maxima, or E. brunetti. No withdrawal period is required to ensure consumer safety. It may also be effective in treating or preventing hepatozoonosis or sarcocystosis myositis. 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. In all trials, the hypothesis tests were conducted at the 0.05 level of significance using twosided tests. 53OECD Draft Guideline: Chironomid Toxicity Test using Spiked Sediment (2002) and BBA Final Draft Guideline: Effect of Plant Protection Products on the Development of Sediment Dwelling Larvae of Chironomus riparius in a Water Sediment System (1995).