Maximum Residue Limits in Veterinary Medicinal Products Regulations

MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS [S.L.231.34 1 SUBSIDIARY LEGISLATION 231.34 MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS REGULATIONS 1st October, 1998 Legal Notice 162 of 1998. Title.1. The title of these Regulations is Maximum Residue Limits in Veterinary Medicinal Products Regulations. Interpretation.2. (1) In these regulations, unless the context otherwise "Director" means the Director for Veterinary Services; "maximum res idue l imi t" or "MRL" means the maximum concentration of residue resulting from the use of a veterinary medicinal product (expressed in mg/Kg or u/Kg on a fresh weight basis) which may be legally permitted or recognised as acceptable in food. This limit is either based on the type and amount of residue considered to be without any toxicological hazard for human health as expressed by the acceptable daily intake (ADI), or on the basis of a temporary ADI that utilises an additional safety factor. In order to assess this limit one also takes into account other relevant public health risks as well as food technology aspects. When establishing a maximum residue limit consideration is also given to residues that are found in food of plant origin and/or come from the envi ronment . Fur thermore , the MRL may be reduced to be consistent with good practices in the use of veterinary drugs and to the extent that practical analytical methods are available; " r e s i d u e s o f v e t e r i n a r y m e d i c i n a l p r o d u c t s " m e a n s a l l pharmacologically active substances, whether active principals, excipients or degradation products, and their metabolites which remain in foodstuffs made from animals to which the veterinary medicinal product in question has been administered. (2) These regulations shall not apply to active principles of biological origin intended to produce active or passive immunity or to diagnose a state of immunity used in immunological veterinary medicinal products. Substances subject to MRL. 3. The list of pharmacologically active substances used in veterinary medicinal products in respect of which maximum residue limits have been established shall be contained in the First Schedule. Substances not subject to MRL. 4. Where, following an evaluation of a pharmacologically active substance used in veterinary medicinal products, it appears that i t is not necessary for the protection of public health to establish a maximum residue limit, that substance shall be included in a list in the Second Schedule. Substances subject to a provisional MRL. 5. The list of pharmacologically active substances used in veterinary medicinal products in respect of which provisional maximum residue limits have been established shall be contained in the Third Schedule. 2 [S.L.231.34 MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS Substances where MRL cannot be fixed. 6. (1) Where it appears that a maximum residue limit cannot be established in respect of a pharmacologically active substance used in veterinary medicinal products because residues of the substances concerned, at whatever limit, in foodstuffs of animal origin constitute a hazard to the health of the consumer, that substance shall be included in a list in the Fourth Schedule. (2) The administration of the substances listed in the Fourth Schedule to food-producing animals shall be prohibited. How to establish MRL. 7. (1) In establishing maximum residue limits for residues of veterinary medicinal products used in foodstuffs of animal origin, it is necessary to specify the animal species in which such residues may be present, the levels which may be present in each of the relevant meat tissues obtained from the treated animal (target tissue), and the nature of the residue which is relevant for the monitoring of residues (marker residue). (2) In order to control for residues, maximum residue limits shall be established for the target t issue of l iver or kidney; however, since liver and kidney are frequently removed from the carcasses marketed in the international trade, maximum residue limits should therefore also always be established for muscle or fat tissues. (3) In the case of veterinary medicinal products intended to be used for laying birds, lactating animals or honey bees, maximum residue limits shall also be established for eggs, milk, or honey. Listing of products. 8. (1) A new pharmacologically active substance, intended to be used in veterinary medicinal products administered to food producing animals, may only be included in the First, Second and Third Schedules if the person responsible for marketing submits a relative application to the Director. Such application shall contain the information and particulars referred to in the Fifth Schedule. (2) The Director may, after assessing new information or after reassessing existing information, amend any provision contained in the First, Second, Third and Fourth Schedules if it is necessary for the protection of human or animal health. (3) The Director may not prohibit or impede the trade of foodstuffs of animal origin and originating in other countries on the ground that they contain residues of veterinary medicinal products if the quantity of residue does not exceed the maximum residue limit found in the First Schedule or in the Third Schedule, or if the substance concerned is listed in the Second Schedule. Food-producing animals. 9. The administration to food-producing animals of veterinary medicinal products containing pharmacologically active substances which are not mentioned in the First, Second or Third Schedules shall be prohibited, except in the case of clinical trials accepted by the competent authorities and provided that foodstuffs obtained from livestock used in such trials do not contain residues which constitute a hazard to human health. Saving. S.L.231.32 10. Nothing in these regulations shall operate against the provisions of the Residues in Meat Regulations, prohibiting the use, in livestock farming, of certain substances which have a MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS [S.L.231.34 3 hormonal action. 4 [S.L.231.34 MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS FIRST SCHEDULE (Regulation 3) List of pharmacologically active substances for which maximum residue limits have been fixed 1. Anti-infectious agents 1.1. Chemotherapeutics 1.1.1. Sulfonamides 1.2. Antibiotics 1.2.1. Penicillins Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues All substances belonging to the sulfonamide group Parent drug All food produc ing species 100 µg/kg Muscle, liver, kidney, fat Bovine, Ovine, Caprine 100 µg/kg Milk Other provisions: The combined total residues of all substances within the sulfonamide group should not exceed 100 µg/kg Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 1.2.1.1. Benzylpenicillin Benzylpenicillin All food produc ing species 50 µg/kg Muscle, liver, kidney, fat 4 µg/kg Milk 1.2.1.2. Ampicillin Ampicillin All food produc ing species 50 µg/kg Muscle, liver, kidney, fat 4 µg/kg Milk 1.2.1.3. Amoxicillin Amoxicillin All food produc ing species 50 µg/kg Muscle, liver, kidney, fat 4 µg/kg Milk 1.2.1.4. Oxacillin Oxacillin All food produc ing species 300 µg/kg Muscle, liver, kidney, fat 30 µg/kg Milk 1.2.1.5. Cloxacillin Cloxacillin All food produc ing species 300 µg/kg Muscle, liver, kidney, fat 30 µg/kg Milk 1.2.1.6. Dicloxacillin Dicloxacillin All food produc ing species 300 µg/kg Muscle, liver, kidney, fat 30 µg/kg Milk 1.2.1.7. Penethamate Benzylpenicillin Bovine 50 µg/kg Muscle, liver, kidney, fat 4 µg/kg Milk MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS [S.L.231.34 5 1.2.2. Cephalosporins 1.2.3. Quinolones 1.2.4. Macrolides 1.2.5. Florfenicol and related compounds Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 1.2.2.1. Cefquinome Cefquinome Bovine 200 µg/kg 100 µg/kg 50 µg/kg 50 µg/kg 20 µg/kg Kidney Liver Muscle Fat Milk Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 1.2.3.1. Enrofloxacin Sum of enrofloxacin and ciprofloxacin Bovine, porcine, poultry 30 µg/kg Muscle, liver kidney 1.2.3.2. Sarafloxacin Sarafloxacin Chicken 100 µg/kg 10 µg/kg Liver Skin and fat 1.2.3.3. Difloxacin Difloxacin Chicken, turkey 200 µg/kg 150 µg/kg 50 µg/kg 200 µg/kg Liver Kidney Muscle Skin and fat Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 1.2.4.1. Tilmicosin Tilmicosin Bovine, ovine, porcine 1000 µg/kg 50 µg/kg Liver, kidney Muscle, fat Ovine 50 µg/kg Milk 1.2.4.2. Spiramycin Sum of spiramycin and neospiramycin Bovine 300 µg/kg 200 µg/kg 200 µg/kg Liver, kidney, fat Muscle Milk Chicken 400 µg/kg 300 µg/kg 200 µg/kg Liver Skin and fat Muscle Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 1.2.5.1. Florfenicol Sum of Florfenicol and its metabolites measured as Florfenicol amine Bovine 200 µg/kg 300 µg/kg 3000 µg/kg Muscle Kidney Liver 6 [S.L.231.34 MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS 1.2.6. Tetracyclines 2. Antiparasitic agents 2.1. Agents acting against endoparasites 2.1.1. Avermectins 2.1.2. Salicylanilides 2.1.3. Tetra-hydro-imidazoles (imidazolthiazoles) Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 1.2.6.1. Tetracycline Sum of parent drug and its 4-epimer All food produc ing species 600 µg/kg 300 µg/kg 100 µg/kg 100 µg/kg 200 µg/kg Kidney Liver Muscle Milk Eggs 1.2.6.2. Oxytetracycline Sum of parent drug and its 4-epimer All food produc ing species 600 µg/kg 300 µg/kg 100 µg/kg 100 µg/kg 200 µg/kg Kidney Liver Muscle Milk Eggs 1.2.6.3. Chlortetracycline Sum of parent drug and its 4-epimer All food produc ing species 600 µg/kg 300 µg/kg 100 µg/kg 100 µg/kg 200 µg/kg Kidney Liver Muscle Milk Eggs Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 2.1.1.1. Ivermectin 22, 23-Dihydro avermectin B 1a Bovine 100 µg/kg 40 µg/kg Liver Fat Porcine, ovine, equidae 15 µg/kg 20 µg/kg Liver Fat 2.1.1.2. Abamectin Avermectin B 1a Bovine 20 µg/kg 10 µg/kg Liver Fat 2.1.1.3. Doramectin Doramectin Bovine 15 µg/kg 25 µg/kg Liver Fat Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 2.1.2.1. Closantel Closantel Bovine 1000 µg/kg 3000 µg/kg Muscle, liver Kidney, fat Ovine 1500 µg/kg 5000 µg/kg 2000 µg/kg Muscle, liver Kidney Fat Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 2.1.2.1. Levamisole Levamisole Bovine, ovine, porcine, poultry 10 µg/kg 100 µg/kg Muscle, kidney, fat Liver MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS [S.L.231.34 7 2.2. Agents acting against ectoparasites 2.2.1. Organophosphates 2.2.2. Formamidines 3. Agents acting on the nervous system 3.1. Agents acting on the autonomic nervous system 3.1.1. Anti-adrenergics SECOND SCHEDULE (Regulation 4) List of substances not subject to maximum residue limits 1. Inorganic chemicals Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 2.2.1.1. Diazinon Diazinon Bovine, ovine 700 µg/kg 20 µg/kg Fat Kidney, liver, muscle Bovine, ovine, caprine 20 µg/kg Milk Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 2.2.2.1. Amitraz Sum of amitraz and all metabo lites containing the 2,4-DMA moeity, expressed as amitraz Porcine 400 µg/kg 200 µg/kg Fat and skin Kidney, liver Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 3.1.1.1. Carazolol Carazolol Porcine 25 µg/kg 5 µg/kg Liver, kidney Muscle, fat and skin Pharmacologically active substance(s) Animal species 1.1. Hydrogen peroxide All food producing species 1.2. Sulphur Bovine, porcine, ovine, caprine, equidae 1.3. Iodine and iodine inorganic compounds including: All food producing species Sodium and potassium-iodide Sodium and potassium-iodate Iodophors including Polyvinyl pyrrolidone-iodine 1.4. Sodium chlorite Bovine (for topical use only) 8 [S.L.231.34 MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS 2. Organic Compounds 1.5. Calcium acetate All food producing species Calcium benzoate Calcium carbonate Calcium chloride Calcium gluconate Calcium hydroxide Calcium hypophosphite Calcium malate Calcium oxide Calcium phosphate Calcium polyphosphates Calcium propionate Calcium silicate Calcium stearate Calcium sulphate 1.6. Hydrochloric acid Al l food producing spec ies ( for use as excipient) 1.7. Sodium dichloroisocyanurate Bovine, ovine, caprine (for topical use only) 1.8. Boric acid and borates All food producing species 1.9. Magnesium All food producing species 1.10. Magnesium sulphate All food producing species 1.11. Magnesium hydroxide All food producing species 1.12. Magnesium stearate All food producing species 1.13. Magnesium glutamate All food producing species 1.14. Magnesium orotate All food producing species 1.15. Magnesium aluminium silicate All food producing species 1.16. Magnesium oxide All food producing species 1.17. Magnesium carbonate All food producing species 1.18. Magnesium phosphate All food producing species 1.19. Magnesium glycerophosphate All food producing species 1.20. Magnesium aspartate All food producing species 1.21. Magnesium citrate All food producing species 1.22. Magnesium acetate All food producing species 1.23. Magnesium trisilicate All food producing species Pharmacologically active substance(s) Animal species 2.1. Etiproston tromethamine Bovine, porcine 2.2. Ketanserin tartrate Equidae 2.3. Fertireline acetate Bovine 2.4. Human menopausal urinary gonadotrophin Bovine 2.5. Lactic acid All food producing species 2.6. Melatonin Ovine, caprine 2.7. Iodine organic compounds Iodoform All food producing species 2.8. Acetyl cysteine All food producing species MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS [S.L.231.34 9 2.9. Gonadotrophin releasing hormone All food producing species 2.10. Pregnant Mare Serum Gonadotrophine All food producing species 2.11. 17ß-Oestradiol A l l f o o d p r o d u c i n g m a m m a l s ( f o r therapeutic and zootechnical uses only) 2.12. Romifidine Equidae (for therapeutic uses only) 2.13. Detomidine Bovine, Equidae (for therapeutic uses only) 2.14. Brotizolam Bovine, (for therapeutic uses only) 2.15. Human chorion gonadotrophin (HCG) All food producing species 2.16. Oxytocin All food producing mammals 2.17. Lecirelin Bovine, equidae, rabbit 2.18. Dinoprost tromethamine All mammalian species 2.19. Malic acid Al l food producing spec ies ( for use as excipient) 2.20. L-tartaric acid and its mono-and dibasic salt of sodium, potassium and calcium All food producing spec ies ( for use as excipient) 2.21. Benzylalcohol Al l food producing spec ies ( for use as excipient) 2.22. Ethanol Al l food producing spec ies ( for use as excipient) 2.23. N-butanol Al l food producing spec ies ( for use as excipient) 2.24. Mineral hydrocarbons, low to high viscosity including microcristalline waxes, approximately C10-C60; aliphatic, branched aliphatic and alicyclic compounds A l l f o o d p r o d u c i n g s p e c i e s ( e x c l u d e s aromatic and unsaturated compounds) 2.25. Buserelin All food producing species 2.26. Ketoprofen Bovine, equidae 2.27. Caffeine All food producing species 2.28. Theophylline All food producing species 2.29. Theobromine All food producing species 2.30. Ketoprofen Porcine 2.31. Propane All food producing species 2.32. e-butane All food producing species 2.33. Isobutane All food producing species 2.34. Polysulphated glycosaminoglycan Equidae 2.35. Rifaximin Bovine (for intramammary use - except if the udder may be used as food for human consumption - and intrauterine use only) 2.36. Tau fluvalinate Honey bees 2.37. Phenol All food producing species 2.38. Papaverine Bovine (newborn calves) 2.39. Policresuline All food producing species (for topical use only) 2.40. Papain All food producing species 2.41. Dimethyl phtalate All food producing species 2.42. Diethyl phtalate All food producing species 2.43. Ethyl lactate All food producing species 10 [S.L.231.34 MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS 3. Substances generally recognized as safe 2.44. Heptaminol All food producing species 2.45. Menthol All food producing species 2.46. Phloroglucinol All food producing species 2.47. Trimethylphloroglucinol All food producing species 2.48. Peracetic acid All food producing species 2.49. Carbetocin All mammalian food producing species 2.50. Quillaia sapocin All food producing species 2.51. Butyl 4-hydroxybenzoate All food producing species 2.52. Sodium butyl 4-hydroxybenzoate All food producing species 2.53. Sodium benzyl 4-hydroxybenzoate All food producing species 2.54. Cetrimide All food producing species 2.55. Lobeline All food producing species 2.56. Pancreatin All mammalian food producing species (for topical use only) 2.57. Chlorocresol All food producing species 2.58. Thymol All food producing species 2.59. Dembrexine Equidae 2.60. Diclazuril Ovine (for oral use in lambs only) 2.61. Etamiphylline camsylate All food producing species Pharmacologically active substance(s) Animal species 3.1. Absinthium extract All food producing species 3.2. Acetylmethionine All food producing species 3.3. Aluminium hydroxide All food producing species 3.4. Aluminium monostearate All food producing species 3.5. Ammonium sulfate All food producing species 3.6. Benzoyl benzoate All food producing species 3.7. Benzyl p-hydroxybenzoate All food producing species 3.8. Calcium borogluconate All food producing species 3.9. Calcium citrate All food producing species 3.10. Camphor All food producing species (external use only) 3.11. Cardamon extract All food producing species 3.12. Diethyl sebacate All food producing species 3.13. Dimethicone All food producing species 3.14. Dimethyl acetamide All food producing species 3.15. Dimethyl sulphoxide All food producing species 3.16. Ethylenediaminetetraacetic acid and salts All food producing species 3.17. Eucalyptol All food producing species 3.18. Epinephrine All food producing species 3.19. Ethyl oleate All food producing species 3.20. Formaldehyde All food producing species 3.21. Formic acid All food producing species 3.22. Follicle stimulating hormone (natural FSH from all species and their synthetic analogues) All food producing species MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS [S.L.231.34 11 3.23. Glutaraldehyde All food producing species 3.24. Guaiacol All food producing species 3.25. Heparin and its salts All food producing species 3.26. Human chorionic gonadotropin (na tu ra l HCG and i t s syn the t i c analogues) All food producing species 3.27. Iron ammonium citrate All food producing species 3.28. Iron dextran All food producing species 3.29. Iron glucoheptonate All food producing species 3.30. Isopropanol All food producing species 3.31. Lanolin All food producing species 3.32. Luteinizing hormone (natural LH from all species and their synthetic analogues) All food producing species 3.33. Magnesium chloride All food producing species 3.34. Magnesium gluconate All food producing species 3.35. Magnesium hypophosphite All food producing species 3.36. Mannitol All food producing species 3.37. Montanide All food producing species 3.38. Methylbenzoate All food producing species 3.39. Monothioglycerol All food producing species 3.40. Myglyol All food producing species 3.41. Orgotein All food producing species 3.42. Poloxalene All food producing species 3.43. Poloxamer All food producing species 3.44. Polyethylene glycol 200 All food producing species 3.45. Polyethylene glycol 400 All food producing species 3.46. Polyethylene glycol 600 All food producing species 3.47. Polyethylene glycol 3500 All food producing species 3.48. Polysorbate 80 All food producing species 3.49. Serotonin All food producing species 3.50. Sodium chloride All food producing species 3.51. Sodium cromoglycate All food producing species 3.52. Sodium dioctylsulphosuccinate All food producing species 3.53. Sodium formaldehydesulphoxylate All food producing species 3.54. Sodium lauryl sulphate All food producing species 3.55. Sodium pyrosulphite All food producing species 3.56. Sodium stearate All food producing species 3.57. Sodium thiosulphate All food producing species 3.58. Tragacanth All food producing species 3.59. Urea All food producing species 3.60. Zinc sulphate All food producing species 3.61. Zinc oxide All food producing species 3.62. Polyethylene glycols (molecular weight ranging from 200 to 10000) All food producing species 12 [S.L.231.34 MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS 4. Substances used in homeopathic veterinary medicinal products 5.1. Substances used as food additives in foodstuffs for human consumption THIRD SCHEDULE (Regulation 5) List of pharmacologically active substances used in veterinary medicinal products for which provisional maximum residue limits have been fixed 1. Anti-infectious agents 1.1. Chemotherapeutics 1.1.1. Diamino pyrimidine derivates 1.1.2. Benzenesulphonamides 1.2. Antibiotics 1.2.2. Macrolides Pharmacologically active substance(s) Animal species 4.1. All substances used in homeopathic veterinary medicinal products provided that their concentration in the product does not exceed one part per ten thousand All food producing species Pharmacologically active substance(s) Animal species 5.1. Substances with an E number All food producing species (only substances approved as additives in foodstuffs for human consumption). Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 1.1.1.1. Trimethoprim Trimethoprim All food produc ing species 50 µg/kg Muscle, liver kidney, fat, milk Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 1.1.2.1. Clorsulon Clorsulon Bovine 50 µg/kg 150 µg/kg 400 µg/kg Muscle Liver Kidney 1.1.2.2. Baquiloprim Baquiloprim Bovine 300 µg/kg 150 µg/kg 10 µg/kg 30 µg/kg Liver Kidney Fat Milk Porcine 50 µg/kg 40 µg/kg Liver, kidney Fat and skin Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 1.2.2.1. Spiramycin Spiramycin Porcine 600 µg/kg 300 µg/kg 200 µg/kg Liver Kidney, muscle Fat I I I I I I MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS [S.L.231.34 13 1.2.3. Thiamphenicol and related compounds 1.2.4. Cephalosporins 1.2.5. Aminoglycosides 1.2.2.2. Tylosin Tylosin Bovine, porcine, poultry 100 µg/kg Muscle, liver kidney Bovine 50 µg/kg Milk 1.2.2.3. Erythromycin Erythromycin Bovine, ovine, porcine, poultry 400 µg/kg Liver, kidney, muscle, fat Bovine, ovine 40 µg/kg Milk Poultry 200 µg/kg Eggs 1.2.2.4. Josamycin Josamycin Chicken 400 µg/kg 200 µg/kg 200 µg/kg Kidney Liver, muscle, fat Eggs Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 1.2.3.1. Thiamphenicol Thiamphenicol Bovine, poultry 40 µg/kg Muscle, liver kidney, fat Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 1.2.4.1. Ceftiofur Sum of all resi dues retaining the betalactam structure expressed as des furoylceftiofur Bovine 2000 µg/kg 200 µg/kg 600 µg/kg 100 µg/kg Kidney, liver Muscle Fat Milk Porcine 4000 µg/kg 3000 µg/kg 500 µg/kg 600 µg/kg Kidney Liver Muscle Fat Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 1.2.5.1. Spectinomycin Spectinomycin Bovine, porcine, poultry 5000 µg/kg 2000 µg/kg 300 µg/kg 500 µg/kg Kidney Liver Muscle Fat Bovine 200 µg/kg Milk 1.2.5.2. Streptomycin Spectinomycin Bovine, ovine, porcine, poultry 1000 µg/kg 500 µg/kg Kidney Muscle, liver, fat Bovine, ovine 200 µg/kg Milk 1.2.5.3. Dihydrostreptomy cin Dihydrostrepto mycin Bovine, ovine, porcine, poultry 1000 µg/kg 500 µg/kg Kidney Muscle, liver, fat Bovine, ovine 200 µg/kg Milk 14 [S.L.231.34 MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS 1.2.6. Quinolones 1.2.7. Naphtalene-ringed ansamycin 1.2.8. Polymyxins 1.2.5.4. Gentamicin Gentamicin Bovine, porcine 1000 µg/kg 200 µg/kg 100 µg/kg Kidney Liver Muscle, fat Bovine 100 µg/kg Milk 1.2.5.5. Neomycin (including framyc etin) Neomycin Bovine, ovine, caprine, porcine, chicken, turkey, duck 5000 µg/kg 500 µg/kg Kidney Muscle, liver, fat Bovine, ovine, caprine 500 µg/kg Milk Chicken 500 µg/kg Eggs 1.2.5.6. Aminosidine Aminosidine Bovine, porcine, rabbits, chicken 1500 µg/kg 500 µg/kg Liver, kidney Muscle Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 1.2.6.1. Danofloxacin Danofloxacin Bovine 900 µg/kg 500 µg/kg 300 µg/kg 200 µg/kg Liver Kidney Muscle Fat Chicken 1200 µg/kg 600 µg/kg 300 µg/kg Liver, kidney Skin and fat Muscle 1.2.6.2. Decoquinate Decoquinate Bovine, ovine 500 µg/kg Muscle, liver Kidney, fat 1.2.6.3. Marbofloxacin Marbofloxacin Bovine 150 µg/kg 75 µg/kg 50 µg/kg Muscle, liver, kidney Milk Fat Porcine 150 µg/kg 50 µg/kg Muscle, liver, kidney Fat and skin Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 1.2.7.1. Rifaximin Rifaximin Bovine 600 µg/kg Milk Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 1.2.8.1. Colistin Colistin Bovine, ovine, porcine, chicken, rabbits 200 µg/kg 150 µg/kg Kidney Liver, muscle, fat Bovine, ovine 50 µg/kg Milk Chicken 300 µg/kg Eggs MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS [S.L.231.34 15 1.2.9. Penicillins 2. Antiparasitic agents 2.1. Agents acting against endo-parasites 2.1.1. Benzimidazoles and pro-benzimidazoles Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 1.2.9.1. Penethamate Benzylpenicillin Ovine 50 µg/kg 4 µg/kg Liver, kidney, muscle, fat Milk Porcine 50 µg/kg Liver, kidney, muscle, fat Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 2.1.1.1. Febantel Combined resi dues of oxfenda zole, oxfendazole sulfone and fen bendazole All food produc ing species 1000 µg/kg 10 µg/kg 10 µg/kg Liver Muscle, kidney, fat Milk Other provisions: The MRLs cover all residues of febantel, fenbendazole and oxfendazole 2.1.1.2. Fenbendazole Combined resi dues of oxfenda zole, oxfendazole sulfone and fen bendazole All food produc ing species 1000 µg/kg 10 µg/kg 10 µg/kg Liver Muscle, kidney, fat Milk Other provisions: The MRLs cover all residues of febantel, fenbendazole and oxfendazole 2.1.1.3. Oxfendazole Combined resi dues of oxfenda zole, oxfendazole sulfone and fen bendazole All food produc ing species 1000 µg/kg 10 µg/kg 10 µg/kg Liver Muscle, kidney, fat Milk Other provisions: The MRLs cover all residues of febantel, fenbendazole and oxfendazole 2.1.1.4. Albendazole Sum of albenda zole and metabo lites which are measured as 2-amino-benzim idazole sulphone Bovine, Ovine 100 µg/kg 500 µg/kg 1000 µg/kg Muscle, fat, milk Kidney Liver 2.1.1.5. Thiabendazole Sum of thiaben dazole and 5-hydroxythia bendazole Bovine, ovine, caprine 100 µg/kg Muscle, liver kidney, fat, milk 2.1.1.6. Triclabendazole Sum of extracta ble residues that may be oxidized to ketatriclaben dazole Bovine, ovine 150 µg/kg 50 µg/kg Muscle, liver, kidney, Fat 16 [S.L.231.34 MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS 2.2. Agents acting against ectoparasites 2.2.1. Formamidines 2.2.2. Organophosphates 2.2.3. Iminophenyl thiazolidine derivative 2.3. Agents acting against endo- and ectoparasites 2 3.1. Avermectins 2.1.1.7. Flubendazole Flubendazole Poultry, game birds 500 µg/kg 200 µg/kg 400 µg/kg Liver Muscle Eggs Porcine 10 µg/kg Muscle, liver kidney, fat 2.1.1.8. Oxibendazole Oxibendazole Bovine, ovine, porcine, equidae 100 µg/kg Muscle, liver kidney, fat Bovine, ovine 50 µg/kg Milk 2.1.1.9. Netobimin Sum of neto bimin and alben dazole and metabolites of albendazole measured as 2-amino-benzim idazole sulphone Bovine, ovine, caprine 1000 µg/kg 500 µg/kg 100 µg/kg 100 µg/kg Liver Kidney Muscle, fat Milk Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 2.2.1.1. Amitraz Sum of amitraz and metabolites which are meas ured as 2,4 dimethylaniline Bovine 200 µg/kg 10 µg/kg Kidney, liver, fat Milk Ovine 400 µg/kg 200 µg/kg Fat Kidney, liver Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 2.2.2.1. Azamethiphos Azamethiphos Salmonidae 100 µg/kg Muscle and skin in natural propor tions Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 2.2.3.1. Cymiazole Cymiazole Bees 1000 µg/kg Honey Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 2.3.1.1. Moxidectin Moxidectin Bovine, ovine 200 µg/kg 20 µg/kg Fat Kidney, liver MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS [S.L.231.34 17 3. Agents acting on the nervous system 3.1. Agents acting on the central nervous system 3.1.1. Butyrophenone tranquillizers 3.2. Agents acting on the automatic nervous system 3.2.1. ß2sympathomimetic agents 4. Corticoids 4.1. Glucocorticoids 5. Anti-inflammatory agents 5.1. Nonsteroidal anti-inflammatory agents 5.1.1. Arylpropionic acid derivative Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 3.1.1.1. Azaperone Azaperol All food produc ing species 100 µg/kg 50 µg/kg Kidney Liver, muscle, fat Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 3.2.1.1. Clenbuterol hydrochloride Clenbuterol Bovine (Indication: solely for tocoly sis in parturient cows) 0,5 µg/kg 0,1 µg/kg 0,05 µg/kg Liver, kidney Muscle Milk Equidae (Indications: tocolysis and the treatment of res piratory ail ments) 0,5 µg/kg 0,1 µg/kg Liver, kidney Muscle Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 4.1.1. Dexamethasone Dexamethasone Bovine, porcine, equidae 2.5 µg/kg 0,5 µg/kg Liver Muscle, kidney Bovine 0,3 µg/kg Milk Pharmacologically active substance(s) Marker residue Animal species MRLs Target tissues 5.1.1.1. Vedaprofen Vedaprofen Equidae 100 µg/kg 1000 µg/kg 50 µg/kg Liver Kidney Muscle 5.1.1.2. Carprofen Carprofen Bovine 1000 µg/kg 500 µg/kg Liver, kidney Muscle, fat Equidae 1000 µg/kg 50 µg/kg 100 µg/kg Liver, kidney Muscle Fat I I I I I 18 [S.L.231.34 MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS FOURTH SCHEDULE (Regulation 6) List of pharmacologically active substances for which no maximum levels can be fixed 1. Nitrofurans, except furazolidone 2. Ronidazole 3. Dapsone 4. Chloramphenicol 5. Furazolidone 6. Dimetridazole 7. Colchicine 8. Avoparcin FIFTH SCHEDULE (Regulation 8) Information and particulars to be included in an application for the establishment of a maximum residue limit for a pharmacologically active substance used in veterinary medicinal products Administrative particulars 1) Name or corporate name and permanent address of the applicant. 2) Name of the veterinary medicinal product. 3) Qualitative and quantitative composition in terms of active principles, with mention of the international non-proprietary name recommended by the World Health Organisation (WHO), where such name exits. 4) Manufacturing authorization, if any. 5) Marketing authorizations, if any. 6) Summary of the characteristics of the veterinary medicinal product(s). A) Safety documentation A.0 Expert report A.1) Precise identification of the substance concerned by the application 1.1) International non-proprietary name. 1.2) International Union of Pure and Applied Chemistry (IUPAC) name. 1.3) Chemical Abstract Service (CAS) name. 1.4) Classification: therapeutic MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS [S.L.231.34 19 pharmacological. 1.5) Synonyms and abbreviations. 1.6) Structural formula. 1.7) Molecular formula. 1.8) Molecular weight. 1.9) Degree of impurity. 1.10) Qualitative and quantitative composition of impurities. 1.11) Description of physical properties: fusion point boiling point vapour pressure solubility in water and organic solvents expressed in g/l, with indication of temperature density refractive index, rotation, etc. A.2) Relevant pharmacological studies 2.1) Pharmacodynamics. 2.2) Pharmacokinetics. A.3) Toxicological studies 3.1) Single dose toxicity. 3.2) Repeated dose toxicity. 3.3) Tolerance in the target species of animal. 3.4) Reproductive toxicity, including teratogenicity. 3.4.1) Study of the effects on reproduction. 3.4.2) Embryotoxicity/fetotoxicity, including teratogenicity. 3.5) Mutagenicity. 3.6) Caricinogenicity. A.4) Studies of other effects 4.1) Immunotoxicity. 4.2) Microbiological properties of residues. 4.2.1) on the human gut flora; 4.2.2) on the organisms and micro-organisms used for industrial food processing. 4.3) Observations in humans. 20 [S.L.231.34 MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS B) Residue documentation B.0) Expert report B.1) Precise identification of the substance concerned by the application The substance concerned should be identified in accordance with item A.1. However, where the application relates to one or more veterinary medicinal products, the product itself should be identified in detail, including: qualitative and quantitative composition; purity; identification of the manufacturer’s batch used in the studies; relationship of the final product; specific activity and radio-purity of labelled substances; position of labelled atoms on the molecule. B.2) Residue studies 2.1) Pharmacokinetics (absorption, distribution, biotransformation, excretion). 2.2) Depletion of residues. 2.3) Elaboration of maximum residue limits (MRLs). B.3) Routine analytical method for the detection of residues 3.1) Description of the method. 3.2) Validation of the method. 3.2.1) specificity; 3.2.2) accuracy, including sensitivity; 3.2.3) precision; 3.2.4) limit of detection; 3.2.5) limit of quantitation; 3.2.6) practicability and applicability under normal laboratory conditions; 3.2.7) susceptibility to interference.