Journal for Veterinary Medicine, Biotechnology and Biosafety

Volume 5, Issue 1, March 2019, Pages 27–33

ISSN 2411-3174 (print version) ISSN 2411-0388 (online version)

DOI: 10.36016/JVMBBS-2019-5-1-6

ACUTE AND SUB-ACUTE TOXICITY ASSESSMENT OFRYBOZURILON COMMON CARP

Yevtushenko A. V., Boyko V. S., Romanko M. Ye.

National Scientific CenterInstitute of Experimental and Clinical Veterinary Medicine’, Kharkiv, Ukraine, e-mail: aevt76@gmail.com

Download PDF (print version)

Citation for print version: Yevtushenko, A. V., Boyko, V. S. and Romanko, M. Ye. (2019) ‘Acute and sub-acute toxicity assessment ofRybozurilon common carp’, Journal for Veterinary Medicine, Biotechnology and Biosafety, 5(1), pp. 27–33.

Download PDF (online version)

Citation for online version: Yevtushenko, A. V., Boyko, V. S. and Romanko, M. Ye. (2019) ‘Acute and sub-acute toxicity assessment ofRybozurilon common carp’, Journal for Veterinary Medicine, Biotechnology and Biosafety. [Online] 5(1), pp. 27–33. DOI: 10.36016/JVMBBS-2019-5-1-6.

Summary. The goal of the work was to study of acute and sub-acute toxicity parameters of ‘Rybozuril’ biological product (AI — diclazuril) on the model of carp. This drug is effective in the treatment of diseases caused by parasitic Eimeriidae. Carp scales of two years old were used in experiments. To determine acute toxicity, the fish were prescribed with diclazuril in doses of 1 g/kg, 5, 10, and 15 g/kg of live weight. Two experimental and control fish groups of 30 individuals each were formed to determine sub-acute toxicity of ‘Rybozuril’. Experimental groups of fish were prescribed with ‘Rybozuril’ in a dose (by AI) of 50 and 10 mg/kg for two consecutive days. Blood samples were collected from six fish from each group for clinical and biochemical indicators after 2, 7, 14, 21, and 28 days. The hemoglobin content, number of red blood cells and leukocytes blood was determined. The intensity of peroxide oxidation of lipids (PОL), catalase activity, level of total antioxidant capacity (TAC), total proteins, albumin, globulins and glucose, circulating immune complexes (CІC) and seromucoids concentration, level of enzymatic activity: aspartate transaminase (АSТ), alanine transaminase (АLТ), α-amylase blood plasma were determined. The acute toxicity of diclazuril for carp was estimated, LD50 is more than 15,000 mg/kg of live weight, the toxicity of diclazuril can be classified as undifferentiated and, in terms of toxicity, it can be classified as hazard class IV. Two administrations of the drug ‘Rybozuril’ in a daily dose of 50.0 mg/kg of live weight, the maximum expression of metabolic changes in fish was detected from the initial terms of the studies and up to day 21. According to the results the toxic effect of the drug in fish was estimated, which did not influence to a number of indicators. The drug in such dose was shown immunosuppression and membrane-toxic effects in fish. Two-time administration of the ‘Rybozuril’ drug in a daily dose of 10.0 mg/kg body weight leads to metabolic alterations in fish due to the activation of detoxification processes and lipoperoxidation maintenance in cell membranes at the physiological level. At the end of the experiment the toxic effect of ‘Rybozuril’ in fish characterized by stable parameters in comparing to the control group.

Keywords: diclazuril, fish, lethal dose, acute toxicity, submerged toxicity, blood, clinical and biochemical indicators

References:

Al-Akel, A. S., Al-Balawi, H. F. A., Al-Misned, F., Mahboob, S., Ahmad, Z. and Suliman, E. M. (2010) ‘Effects of dietary copper exposure on accumulation, growth, and hematological parameters in Cyprinus carpio’, Toxicological and Environmental Chemistry, 92(10), pp. 1865–1878. http://dx.doi.org/10.1080/02772248.2010.486230

CEC (The Council of the European Communities). (1986) ‘Council Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes’, The Official Journal of the European Communities, L 358, pp. 1–28. Available at: http://data.europa.eu/eli/dir/1986/609/oj

Conway, D. P., Mathis, G. F., Johnson, J., Schwartz, M. and Baldwin, C. (2001) ‘Efficacy of diclazuril in comparison with chemical and ionophorous anticoccidials against Eimeria spp. in broiler chickens in floor pens’, Poultry Science, 80(4), pp. 426–430. http://dx.doi.org/10.1093/ps/80.4.426

De Bono, D. (1994) ‘Free radicals and antioxidants in vascular biology: the roles of reaction kinetics, environment and substrate turnover’, QJM: Monthly Journal of the Association of Physicians, 89(8), pp. 445–453. http://dx.doi.org/10.1093/oxfordjournals.qjmed.a068954

Demidov, N. V. and Berezkina, S. V. (1986) Guidelines for assessment of anthelmintics in veterinary medicine [Metodicheskie rekomendatsii po otsenke angel’mintikov v veterinarii]. Moscow: VASKhNIL. [in Russian]

Dirksen, G. (1990) ‘Liver [Leber]’, in Dirksen, G., Gründer, H. D. and Stöber, M. (eds.) Rosenberger, G. Clinical examination of cattle [Die klinische Untersuchung des Rindes]. 3rd ed. Berlin, Hamburg: Paul Parey, pp. 367–384. ISBN 9783830440383. [in German]

EMEA (European Medicines Agency) (1996) Diclazuril — summary report (1). Report of the Committee for Veterinary Medicinal Products. EMEA/MRL/086/96-FINAL. Available at: https://www.ema.europa.eu/en/documents/mrl-report/diclazuril-summary-report-1-committee-veterinary-medicinal-products_en.pdf

FEEDAP (EFSA Panel on Additives and Products or Substances used in Animal Feed) (2014) ‘Scientific Opinion on the safety and efficacy of Coxiril® (diclazuril) as a feed additive for turkeys for fattening: Coxiril® (diclazuril) for turkeys for fattening’, EFSA Journal, 12(6), p. 3729. http://dx.doi.org/10.2903/j.efsa.2014.3729

FEEDAP (EFSA Panel on Additives and Products or Substances used in Animal Feed) (2015) ‘Scientific Opinion on the safety and efficacy of Coxiril® (diclazuril) for rabbits for fattening and breeding: Coxiril® (diclazuril) for rabbits for fattening and breeding’, EFSA Journal, 13(1), p. 3968. http://dx.doi.org/10.2903/j.efsa.2015.3968

Gavrilov, V. B. and Mishkorudnaya, M. I. (1983) ‘Spectrophotometric determination of the content of lipid hydroperoxides in blood plasma’ [Spektrofotometricheskoe opredelenie soderzhaniya gidroperekisey lipidov v plazme krovi], Laboratory Science [Laboratornoe delo], 3, pp. 33–36. [in Russian]

GOST 12.1.007-76. Occupational safety standards system. Noxious substances. Classification and general safety requirements [Sistema standartov bezopasnosti truda. Vrednye veshchestva. Klassifikatsiya i obshchie trebovaniya bezopasnosti]. [in Russian]

Khazanov, A. I. (1988) Functional diagnosis of liver diseases [Funktsional’naya diagnostika bolezney pecheni]. 2nd ed. Moscow: Meditsina. ISBN 522500069X. [in Russian]

Klebanov, G. I., Babenkova, I. V., Teselkin, Yu. O., Komarov, O. S. and Vladimirov, Yu. A. (1988) ‘Evaluation of the antioxidative activity of blood plasma using yolk lipoproteins’ [Otsenka antiokislitel’noy aktivnosti plazmy krovi s primeneniem zheltochnykh lipoproteidov], Laboratory Science [Laboratornoe delo], 5, pp. 59–62. PMID: 2459459. [in Russian]

Kondrakhin, I. P., Kurilov, N. V., Malakhov, A. G., Arkhipov, A. V., Belov, A. D., Belyakov, I. M., Blinov, N. I., Korobov, A. V., Frolova, L. A. and Sevast’yanova, N. A. (1985) Clinical laboratory diagnostics in veterinary medicine [Klinicheskaya laboratornaya diagnostika v veterinarii]. Moscow: Agropromizdat. [in Russian]

Korolyuk, M. A., Ivanova, L. I., Mayorova, I. G. and Tokarev, V. E. (1988) ‘Determination of catalase activity’ [Opredelenie aktivnosti katalaz], Laboratory Science [Laboratornoe delo], 1, pp. 16–18. PMID: 2451064. [in Russian]

Kotsiumbas, I. Ya., Malyk, O. H., Patereha, I. P., Tishyn, O. L. and Kosenko, Yu. M. (2006) Preclinical studies of veterinary drugs [Doklinichni doslidzhennia veterynarnykh likarskykh zasobiv]. Lviv: Triada plus. ISBN 9667596648. [in Ukrainian]

Levinsky, R. J. (1981) ‘Role of circulating immune complexes in renal diseases’, Journal of Clinical Pathology, 34(11), pp. 1214–1222. http://dx.doi.org/10.1136/jcp.34.11.1214

Maltsev, V. N. (2012) ‘About parasitological situation in carp hatcheries of the south regions of Ukraine’ [O parazitologicheskoy situatsii v karpovykh rybopitomnikakh yuzhnykh oblastey Ukrainy], Modern Problems of Theoretical and Practical Ichthyology: Proceedings of the 5th International Ichthyologic Scientific and Practical Conference (Chernivtsi, 13–16 September 2012) [Suchasni problemy teoretychnoi i praktychnoi ikhtiolohii: materialymizhnarodnoi ikhtiolohichnoi naukovo-praktychnoi konferentsii (Chernivtsi, 13–16 veresnia 2012 r.)]. Chernivtsi: Knyhy-XXI, pp. 142–148. Available at: https://www.eco-tiras.org/docs/berg/Cernauti-kof_ichthyo_chernivtsi_2012.pdf. [in Russian]

Marques, G. L., Neto, F. F., Ribeiro, C. A. de O., Liebel, S., Fraga, R. de and Bueno, R. da R. L. (2015) ‘Oxidative damage in the aging heart: an experimental rat model’, The Open Cardiovascular Medicine Journal, 9(1), pp. 78–82. http://dx.doi.org/10.2174/1874192401509010078

Medved’, L. I., Kagan, Yu. S. and Spynu, Ye. I. (1968) ‘Pesticides and health problems’ [Pestitsidy i problemy zdravookhraneniya], Journal of the D. I. Mendeleev All-Union Chemical Society [Zhurnal Vsesoyuznogo khimicheskogo obshchestva imeni D. I. Mendeleeva], 13(3), pp. 263–271

Men’shikov, V. V. (ed.) (1987) Laboratory research methods in the clinic [Laboratornye metody issledovaniya v klinike]. Moscow: Meditsina. [in Russian]

Molnár, K. and Ostoros, G. (2007) ‘Efficacy of some anticoccidial drugs for treating coccidial enteritis of the common carp caused by Goussia carpelli (Apicomplexa: Eimeriidae)’, Acta Veterinaria Hungarica, 55(1), pp. 67–76. http://dx.doi.org/10.1556/AVet.55.2007.1.7

Selifanova, E. A. and Birukova, N. P. (2012) ‘Subchronic toxicity of Eimeterm diclazuril’ [Subkhronicheskaya toksichnostpreparata Eymeterm diclazuril], Theory and Practice of Struggle Against Parasitic Diseases [Teoriya i praktika bor’by s parazitarnymi boleznyami], 13, pp. 385–387. Available at: https://elibrary.ru/item.asp?id=30311107. [in Russian]

Tokarev, A. N., Selifanova, E. A., Napalkova, V. V. and Zhuravleva, A. Z. (2012) ‘Comparative evaluation of acute toxicities of Eimeterm diklazuril and Diacox’ [Sravnitel’naya otsenka ostroy toksichnosti preparatov Eymeterm diklazurila i Diakoksa], Theory and Practice of Struggle Against Parasitic Diseases [Teoriya i praktika bor’by s parazitarnymi boleznyami], 13, pp. 418–421. Available at: https://elibrary.ru/item.asp?id=30311119. [in Russian]

Trombitskiy, I. D. and Bushuev, S. G. (eds.) (2011) Comprehensive Moldovan-Ukrainian studies of the ichthyofauna of the Lower Dniester basin —2011 [Kompleksnye moldo-ukrainskie issledovaniya ikhtiofauny vodoemov basseyna Nizhnego Dnestra — 2011]. Project report. Available at: http://www.eco-tiras.org/docs/DniesterFishReport2011.pdf. [in Russian]

Verheyen, A., Maes, L., Coussement, W., Vanparijs, O., Lauwers, F., Vlaminckx, E., Borgers, M. and Marsboom, R. (1988) ‘In vivo action of the anticoccidial diclazuril (Clinacox®) on the developmental stages of Eimeria tenella: an ultrastructural evaluation’, The Journal of Parasitology, 74(6), pp. 939–949. http://dx.doi.org/10.2307/3282213

Vlizlo, V. V. (ed.) (2012) Laboratory methods of research in biology, animal husbandry and veterinary medicine [Laboratorni metody doslidzhen u biolohii, tvarynnytstvi ta veterynarnii medytsyni]. Lviv: Spolom. ISBN 9769666656776. [in Ukrainian]