L.S. 449.19 Regolamenti dwar Limiti Massimi ta’ Fdalijiet fi Prodotti Mediċinali Veterinarji

(1)In these regulations, unless the context otherwise - Title. Interpretation. "Director" means the Director for Veterinary Services; "m axim um r esid ue lim it" or "MRL " m eans t he m axim um 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 en v ir o n m ent . Fu r th er m o r e, th e MR L m ay b e r ed u ced to b e consistent with good practices in the use of veterinary drugs and to the extent that practical analytical methods are available; "residues of veterinary medicinal products" means all 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.

1. 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 subject to MRL.
2. Where, following an evaluation of a pharmacologically active substance used in veterinary medicinal products, it appears that it 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 not subject to MRL.
3. 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. Substances subject to a provisional MRL. 2 [ S.L.449.19 Substances where MRL cannot be fixed. MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS 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 tissue of liver 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. 449.18 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 hormonal action. MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS [ S.L.449.19 3 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 Pharmacologically active Marker residue Animal species MRLs Target tissues substance(

1. s)All substances Parent drug All food produc- 100 µ g/kg Muscle, liver, ing species kidney, fat belonging to the sulfonamide group Bovine, Ovine, 100 µ g/kg Milk Caprine Other provisions: The combined total residues of all substances within the sulfonamide group should not exceed 100 µ g/kg 1.2. 1.2.1. Antibiotics Penicillins Pharmacologically active Marker residue Animal species MRLs substance(
2. s)1.2.1.1. Benzylpenicillin All food produc- 50 µ g/kg Benzylpenicillin ing species 4 µ g/kg 1.2.1.2. Ampicillin All food produc- 50 µ g/kg Ampicillin ing species 4 µ g/kg 1.2.1.3. Amoxicillin All food produc- 50 µ g/kg Amoxicillin ing species 4 µ g/kg 1.2.1.4. Oxacillin All food produc- 300 µ g/kg Oxacillin ing species 30 µ g/kg 1.2.1.5. Cloxacillin All food produc- 300 µ g/kg Cloxacillin ing species 30 µ g/kg 1.2.1.6. Dicloxacillin All food produc- 300 µ g/kg Dicloxacillin ing species 30 µ g/kg 1.2.1.7. Benzylpenicillin Bovine 50 µ g/kg Penethamate 4 µ g/kg Target tissues Muscle, liver, kidney, fat Milk Muscle, liver, kidney, fat Milk Muscle, liver, kidney, fat Milk Muscle, liver, kidney, fat Milk Muscle, liver, kidney, fat Milk Muscle, liver, kidney, fat Milk Muscle, liver, kidney, fat Milk [ S.L.449.19 4 1.2.2. Cephalosporins Pharmacologically active Marker residue substance(
3. s)1.2.2.1. Cefquinome Cefquinome 1.2.3. Animal species Bovine 200 µ g/kg 100 µ g/kg 50 µ g/kg 50 µ g/kg 20 µ g/kg Target tissues Kidney Liver Muscle Fat Milk Animal species MRLs Target tissues Bovine, porcine, 30 µ g/kg poultry Muscle, liver kidney Chicken Liver Skin and fat Liver Kidney Muscle Skin and fat Chicken, turkey 100 µ g/kg 10 µ g/kg 200 µ g/kg 150 µ g/kg 50 µ g/kg 200 µ g/kg Macrolides Pharmacologically active Marker residue substance(
4. s)1.2.4.1. Tilmicosin Tilmicosin 1.2.4.2. Spiramycin Sum of spiramycin and neospiramycin Animal species Bovine, ovine, porcine Ovine Bovine Chicken 1.2.5. MRLs Quinolones Pharmacologically active Marker residue substance(
5. s)1.2.3.1. Sum of Enrofloxacin enrofloxacin and ciprofloxacin 1.2.3.2. Sarafloxacin Sarafloxacin 1.2.3.3. Difloxacin Difloxacin 1.2.4. MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS MRLs Target tissues 1000 µ g/kg 50 µ g/kg 50 µ g/kg 300 µ g/kg 200 µ g/kg 200 µ g/kg 400 µ g/kg 300 µ g/kg 200 µ g/kg Liver, kidney Muscle, fat Milk Liver, kidney, fat Muscle Milk Liver Skin and fat Muscle MRLs Target tissues Florfenicol and related compounds Pharmacologically active Marker residue substance(
6. s)1.2.5.1. Sum of Florfenicol Florfenicol and its metabolites measured as Florfenicolamine Animal species Bovine 200 µ g/kg 300 µ g/kg 3000 µ g/kg Muscle Kidney Liver MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS 1.2.6. [ S.L.449.19 Tetracyclines Pharmacologically active Marker residue Animal species MRLs substance(
7. s)1.2.6.1. Sum of parent All food produc- 600 µ g/kg Tetracycline drug and its ing species 300 µ g/kg 4-epimer 100 µ g/kg 100 µ g/kg 200 µ g/kg 1.2.6.2. Sum of parent All food produc- 600 µ g/kg Oxytetracycline drug and its ing species 300 µ g/kg 4-epimer 100 µ g/kg 100 µ g/kg 200 µ g/kg All food produc- 600 µ g/kg 1.2.6.3. Sum of parent ing species 300 µ g/kg Chlortetracycline drug and its 4-epimer 100 µ g/kg 100 µ g/kg 200 µ g/kg 2. 2.1. 2.1.1. MRLs 100 µ g/kg 40 µ g/kg 15 µ g/kg 20 µ g/kg 20 µ g/kg 10 µ g/kg 15 µ g/kg 25 µ g/kg Kidney Liver Muscle Milk Eggs Kidney Liver Muscle Milk Eggs Kidney Liver Muscle Milk Eggs Target tissues Liver Fat Liver Fat Liver Fat Liver Fat Salicylanilides Pharmacologically active Marker residue Animal species MRLs substance(
8. s)2.1.2.1. Closantel Bovine 1000 µ g/kg Closantel 3000 µ g/kg Ovine 1500 µ g/kg 5000 µ g/kg 2000 µ g/kg 2.1.3. Target tissues Antiparasitic agents Agents acting against endoparasites Avermectins Pharmacologically active Marker residue Animal species substance(
9. s)2.1.1.1. 22, 23-Dihydro- Bovine Ivermectin avermectin B 1a Porcine, ovine, equidae 2.1.1.2. Avermectin B 1a Bovine Abamectin 2.1.1.3. Doramectin Bovine Doramectin 2.1.2. 5 Target tissues Muscle, liver Kidney, fat Muscle, liver Kidney Fat Tetra-hydro-imidazoles (imidazolthiazoles) Pharmacologically active Marker residue Animal species MRLs substance(
10. s)2.1.2.1. Levamisole Bovine, ovine, 10 µ g/kg Levamisole porcine, poultry 100 µ g/kg Target tissues Muscle, kidney, fat Liver MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS [ S.L.449.19 6 2.2. 2.2.1. Agents acting against ectoparasites Organophosphates Pharmacologically active Marker residue substance(
11. s)2.2.1.1. Diazinon Diazinon 2.2.2. MRLs Bovine, ovine 700 µ g/kg 20 µ g/kg Bovine, ovine, caprine 20 µ g/kg Target tissues Fat Kidney, liver, muscle Milk Formamidines Pharmacologically active Marker residue substance(
12. s)2.2.2.1. Sum of amitraz Amitraz and all metabolites containing the 2,4-DMA moeity, expressed as amitraz 3. 3.1. 3.1.1. Animal species Animal species Porcine MRLs 400 µ g/kg 200 µ g/kg Target tissues Fat and skin Kidney, liver Agents acting on the nervous system Agents acting on the autonomic nervous system Anti-adrenergics Pharmacologically active Marker residue substance(
13. s)3.1.1.1. Carazolol Carazolol Animal species Porcine MRLs 25 µ g/kg 5 µ g/kg Target tissues Liver, kidney Muscle, fat and skin SECOND SCHEDULE 1. (Regulation 4) List of substances not subject to maximum residue limits Inorganic chemicals Pharmacologically active substance(
14. s)1.1. Hydrogen peroxide 1.2. Sulphur 1.3. Iodine and iodine inorganic compounds including: - Sodium and potassium-iodide - Sodium and potassium-iodate - Iodophors including Polyvinylpyrrolidone-iodine 1.4. Sodium chlorite Animal species All food producing species Bovine, porcine, ovine, caprine, equidae All food producing species Bovine (for topical use only) MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS 1.5. 1.6. Calcium acetate 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 Hydrochloric acid 1.7. Sodium dichloroisocyanurate 1.8. Boric acid and borates 1.9. Magnesium 1.10. Magnesium sulphate 1.11. Magnesium hydroxide 1.12. Magnesium stearate 1.13. Magnesium glutamate 1.14. Magnesium orotate 1.15. Magnesium aluminium silicate 1.16. Magnesium oxide 1.17. Magnesium carbonate 1.18. Magnesium phosphate 1.19. Magnesium glycerophosphate 1.20. Magnesium aspartate 1.21. Magnesium citrate 1.22. Magnesium acetate 1.23. Magnesium trisilicate 2. [ S.L.449.19 All food producing species All food producing species (for use as excipient) Bovine, ovine, caprine (for topical use only) All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species Organic Compounds Pharmacologically active substance(
15. s)2.1. Etiproston tromethamine 2.2. Ketanserin tartrate 2.3. Fertireline acetate 2.4. Human menopausal urinary gonadotrophin 2.5. Lactic acid 2.6. Melatonin 2.7. Iodine organic compounds - Iodoform 2.8. Acetyl cysteine 7 Animal species Bovine, porcine Equidae Bovine Bovine All food producing species Ovine, caprine All food producing species All food producing species 8 MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS [ S.L.449.19 2.9. Gonadotrophin releasing hormone 2.10. Pregnant Mare Serum Gonadotrophine 2.11. 17ß-Oestradiol All food producing species All food producing species All food producing mammals (for therapeutic and zootechnical uses only) Equidae (for therapeutic uses only) Bovine, Equidae (for therapeutic uses only) Bovine, (for therapeutic uses only) gonadotrophin All food producing species 2.12. Romifidine 2.13. Detomidine 2.14. Brotizolam 2.15. Human chorion (HCG) 2.16. Oxytocin 2.17. Lecirelin 2.18. Dinoprost tromethamine 2.19. Malic acid All food producing mammals Bovine, equidae, rabbit All mammalian species A l l fo o d p ro d u c i n g s p e c ie s ( fo r u s e a s excipient) 2.20. L-tartaric acid and its mono-and A l l fo o d p ro d u c i n g s p e c ie s ( fo r u s e a s dibasic salt of sodium, potassium excipient) and calcium 2.21. Benzylalcohol A l l fo o d p ro d u c i n g s p e c ie s ( fo r u s e a s excipient) 2.22. Ethanol A l l fo o d p ro d u c i n g s p e c ie s ( fo r u s e a s excipient) 2.23. N-butanol A l l fo o d p ro d u c i n g s p e c ie s ( fo r u s e a s excipient) 2.24. Mineral hydrocarbons, low to high All food producing species (excludes viscosity including microcristalline aromatic and unsaturated compounds) w ax es, a pp ro xim ately C1 0-C6 0 ; aliphatic, branched aliphatic and alicyclic 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 ud der ma y be use d as fo od fo r hu man 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 MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS 2.43. Ethyl lactate 2.44. Heptaminol 2.45. Menthol 2.46. Phloroglucinol 2.47. Trimethylphloroglucinol 2.48. Peracetic acid 2.49. Carbetocin 2.50. Quillaia sapocin 2.51. Butyl 4-hydroxybenzoate 2.52. Sodium butyl 4-hydroxybenzoate 2.53. Sodium benzyl 4-hydroxybenzoate 2.54. Cetrimide 2.55. Lobeline 2.56. Pancreatin 2.57. Chlorocresol 2.58. Thymol 2.59. Dembrexine 2.60. Diclazuril 2.61. Etamiphylline camsylate 3. [ S.L.449.19 9 All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All mammalian food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All mammalian food producing species (for topical use only) All food producing species All food producing species Equidae Ovine (for oral use in lambs only) All food producing species Substances generally recognized as safe Pharmacologically active substance(
16. s)3.1. Absinthium extract 3.2. Acetylmethionine 3.3. Aluminium hydroxide 3.4. Aluminium monostearate 3.5. Ammonium sulfate 3.6. Benzoyl benzoate 3.7. Benzyl p-hydroxybenzoate 3.8. Calcium borogluconate 3.9. Calcium citrate 3.10. Camphor 3.11. Cardamon extract 3.12. Diethyl sebacate 3.13. Dimethicone 3.14. Dimethyl acetamide 3.15. Dimethyl sulphoxide 3.16. Ethylenediaminetetraacetic and salts 3.17. Eucalyptol 3.18. Epinephrine 3.19. Ethyl oleate 3.20. Formaldehyde 3.21. Formic acid Animal species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species (external use only) All food producing species All food producing species All food producing species All food producing species All food producing species acid All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species 10 [ S.L.449.19 MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS 3.22. Follicle stimulating hormone (natural FSH from all species and their synthetic analogues) 3.23. Glutaraldehyde 3.24. Guaiacol 3.25. Heparin and its salts 3.26. Human chorionic gonadotropin (natural HCG and its synthetic analogues) 3.27. Iron ammonium citrate 3.28. Iron dextran 3.29. Iron glucoheptonate 3.30. Isopropanol 3.31. Lanolin 3.32. Luteinizing hormone (natural LH from all species and their synthetic analogues) 3.33. Magnesium chloride 3.34. Magnesium gluconate 3.35. Magnesium hypophosphite 3.36. Mannitol 3.37. Montanide 3.38. Methylbenzoate 3.39. Monothioglycerol 3.40. Myglyol 3.41. Orgotein 3.42. Poloxalene 3.43. Poloxamer 3.44. Polyethylene glycol 200 3.45. Polyethylene glycol 400 3.46. Polyethylene glycol 600 3.47. Polyethylene glycol 3500 3.48. Polysorbate 80 3.49. Serotonin 3.50. Sodium chloride 3.51. Sodium cromoglycate 3.52. Sodium dioctylsulphosuccinate 3.53. Sodium formaldehydesulphoxylate 3.54. Sodium lauryl sulphate 3.55. Sodium pyrosulphite 3.56. Sodium stearate 3.57. Sodium thiosulphate 3.58. Tragacanth 3.59. Urea 3.60. Zinc sulphate 3.61. Zinc oxide All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species All food producing species MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS 3.62. Polyethylene glycols (molecular weight ranging from 200 to 10000) 4. 11 All food producing species Substances used in homeopathic veterinary medicinal products Pharmacologically active substance(
17. s)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 5.1. [ S.L.449.19 Animal species All food producing species Substances used as food additives in foodstuffs for human consumption Pharmacologically active substance(
18. s)5.1. Substances with an E number Animal species All food producing species (only substances approved as 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 Pharmacologically active Marker residue Animal species MRLs substance(
19. s)1.1.1.1. Trimethoprim All food produc- 50 µ g/kg Trimethoprim ing species Target tissues Muscle, liver kidney, fat, milk 1.1.2. Benzenesulphonamides Pharmacologically active Marker residue Animal species MRLs substance(
20. s)1.1.2.1. Clorsulon Bovine 50 µ g/kg Clorsulon 150 µ g/kg 400 µ g/kg 1.1.2.2. Baquiloprim Bovine 300 µ g/kg Baquiloprim 150 µ g/kg 10 µ g/kg 30 µ g/kg Porcine 50 µ g/kg 40 µ g/kg Target tissues Muscle Liver Kidney Liver Kidney Fat Milk Liver, kidney Fat and skin 1.2. Antibiotics 1.2.2. Macrolides Pharmacologically active substance(
21. s)Marker residue Animal species MRLs Target tissues 12 [ S.L.449.19 1.2.2.1. Spiramycin Spiramycin 1.2.2.2. Tylosin Tylosin 1.2.2.3. Erythromycin Erythromycin 1.2.2.4. Josamycin Josamycin MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS Porcine 600 µ g/kg 300 µ g/kg 200 µ g/kg Bovine, porcine, 100 µ g/kg poultry Bovine 50 µ g/kg Bovine, ovine, 400 µ g/kg porcine, poultry Bovine, ovine 40 µ g/kg Poultry 200 µ g/kg Chicken 400 µ g/kg 200 µ g/kg 200 µ g/kg Liver Kidney, muscle Fat Muscle, liver kidney Milk Liver, kidney, muscle, fat Milk Eggs Kidney Liver, muscle, fat Eggs 1.2.3. Thiamphenicol and related compounds Pharmacologically active Marker residue substance(
22. s)1.2.3.1. Thiamphenicol Thiamphenicol Animal species Bovine, poultry MRLs 40 µ g/kg Target tissues Muscle, liver kidney, fat 1.2.4. Cephalosporins Pharmacologically active Marker residue Animal species substance(
23. s)1.2.4.1. Sum of all resi- Bovine Ceftiofur dues retaining the betalactam structure expressed as desfuroylceftiofur Porcine MRLs Target tissues 2000 µ g/kg 200 µ g/kg 600 µ g/kg 100 µ g/kg Kidney, liver Muscle Fat Milk 4000 µ g/kg 3000 µ g/kg 500 µ g/kg 600 µ g/kg Kidney Liver Muscle Fat 1.2.5. Aminoglycosides Pharmacologically active Marker residue substance(
24. s)1.2.5.1. Spectinomycin Spectinomycin 1.2.5.2. Streptomycin Spectinomycin 1.2.5.3. DihydrostreptoDihydrostreptomy- mycin cin Animal species MRLs Target tissues Bovine, porcine, 5000 µ g/kg poultry 2000 µ g/kg 300 µ g/kg 500 µ g/kg Bovine 200 µ g/kg Bovine, ovine, 1000 µ g/kg porcine, poultry 500 µ g/kg Bovine, ovine 200 µ g/kg Bovine, ovine, 1000 µ g/kg porcine, poultry 500 µ g/kg Kidney Liver Muscle Fat Milk Kidney Muscle, liver, fat Milk Kidney Muscle, liver, fat Bovine, ovine Milk 200 µ g/kg MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS 1.2.5.4. Gentamicin Gentamicin 1.2.5.5. Neomycin Neomycin (including framycetin) 1.2.5.6. Aminosidine Aminosidine [ S.L.449.19 Bovine, porcine 1000 µ g/kg 200 µ g/kg 100 µ g/kg Bovine 100 µ g/kg Bovine, ovine, 5000 µ g/kg caprine, porcine, 500 µ g/kg chicken, turkey, duck Bovine, ovine, 500 µ g/kg caprine Chicken 500 µ g/kg Bovine, porcine, 1500 µ g/kg rabbits, chicken 500 µ g/kg 13 Kidney Liver Muscle, fat Milk Kidney Muscle, liver, fat Milk Eggs Liver, kidney Muscle 1.2.6. Quinolones Pharmacologically active Marker residue Animal species MRLs substance(
25. s)1.2.6.1. Danofloxacin Bovine 900 µ g/kg Danofloxacin 500 µ g/kg 300 µ g/kg 200 µ g/kg Chicken 1200 µ g/kg 600 µ g/kg 300 µ g/kg 1.2.6.2. Decoquinate Bovine, ovine 500 µ g/kg Decoquinate 1.2.6.3. Marbofloxacin Bovine 150 µ g/kg Marbofloxacin 75 µ g/kg 50 µ g/kg Porcine 150 µ g/kg 50 µ g/kg Target tissues Liver Kidney Muscle Fat Liver, kidney Skin and fat Muscle Muscle, liver Kidney, fat Muscle, liver, kidney Milk Fat Muscle, liver, kidney Fat and skin 1.2.7. Naphtalene-ringed ansamycin Pharmacologically active Marker residue Animal species MRLs substance(
26. s)1.2.7.1. Rifaximin Bovine 600 µ g/kg Rifaximin Target tissues Milk 1.2.8. Polymyxins Pharmacologically active Marker residue Animal species substance(
27. s)1.2.8.1. Colistin Bovine, ovine, Colistin porcine, chicken, rabbits Bovine, ovine Chicken MRLs Target tissues 200 µ g/kg 150 µ g/kg Kidney Liver, muscle, fat 50 µ g/kg 300 µ g/kg Milk Eggs 14 [ S.L.449.19 MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS 1.2.9. Penicillins Pharmacologically active Marker residue Animal species MRLs substance(
28. s)1.2.9.1. Benzylpenicillin Ovine 50 µ g/kg Penethamate 4 µ g/kg Porcine 50 µ g/kg Target tissues Liver, kidney, muscle, fat Milk Liver, kidney, muscle, fat 2. Antiparasitic agents 2.1. Agents acting against endo-parasites 2.1.1. Benzimidazoles and pro-benzimidazoles Pharmacologically active Marker residue Animal species MRLs Target tissues substance(
29. s)2.1.1.1. Combined resi- All food produc- 1000 µ g/kg Liver 10 µ g/kg Muscle, kidney, Febantel dues of oxfenda- ing species fat zole, oxfendazole sulfone and fen10 µ g/kg Milk bendazole Other provisions: The MRLs cover all residues of febantel, fenbendazole and oxfendazole 2.1.1.2. Combined resi- All food produc- 1000 µ g/kg Liver Fenbendazole dues of oxfenda- ing species 10 µ g/kg Muscle, kidney, zole, oxfendazole fat sulfone and fen10 µ g/kg Milk bendazole Other provisions: The MRLs cover all residues of febantel, fenbendazole and oxfendazole 2.1.1.3. Combined resi- All food produc- 1000 µ g/kg Liver Oxfendazole dues of oxfenda- ing species 10 µ g/kg Muscle, kidney, zole, oxfendazole fat sulfone and fen10 µ g/kg Milk bendazole Other provisions: The MRLs cover all residues of febantel, fenbendazole and oxfendazole 2.1.1.4. Sum of albenda- Bovine, Ovine 100 µ g/kg Muscle, fat, milk Albendazole zole and metabo500 µ g/kg Kidney lites which are 1000 µ g/kg Liver measured as 2-amino-benzimidazole sulphone 2.1.1.5. Sum of thiaben- Bovine, ovine, 100 µ g/kg Muscle, liver Thiabendazole dazole and caprine kidney, fat, milk 5-hydroxythiabendazole 150 µ g/kg Muscle, liver, Sum of extracta- Bovine, ovine 2.1.1.6. kidney, Triclabendazole ble residues that 50 µ g/kg Fat may be oxidized to ketatriclabendazole MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS 2.1.1.7. Flubendazole Flubendazole Poultry, game birds Porcine 2.1.1.8. Oxibendazole 2.1.1.9. Netobimin Oxibendazole Bovine, ovine, porcine, equidae Bovine, ovine Bovine, ovine, Sum of netobimin and alben- caprine dazole and metabolites of albendazole measured as 2-amino-benzimidazole sulphone [ S.L.449.19 500 µ g/kg 200 µ g/kg 400 µ g/kg 10 µ g/kg 100 µ g/kg 50 µ g/kg 1000 µ g/kg 500 µ g/kg 100 µ g/kg 100 µ g/kg 15 Liver Muscle Eggs Muscle, liver kidney, fat Muscle, liver kidney, fat Milk Liver Kidney Muscle, fat Milk 2.2. Agents acting against ectoparasites 2.2.1. Formamidines Pharmacologically active Marker residue Animal species MRLs substance(
30. s)2.2.1.1. Sum of amitraz Bovine 200 µ g/kg Amitraz and metabolites 10 µ g/kg which are measured as 2,4dimethylaniline Ovine 400 µ g/kg 200 µ g/kg Target tissues Kidney, liver, fat Milk Fat Kidney, liver 2.2.2. Organophosphates Pharmacologically active Marker residue Animal species MRLs substance(
31. s)2.2.2.1. Azamethiphos Salmonidae 100 µ g/kg Azamethiphos Target tissues Muscle and skin in natural proportions 2.2.3. Iminophenyl thiazolidine derivative Pharmacologically active Marker residue Animal species MRLs substance(
32. s)2.2.3.1. Cymiazole Bees 1000 µ g/kg Cymiazole Target tissues Honey 2.3. Agents acting against endo- and ectoparasites 2 3.1. Avermectins Pharmacologically active Marker residue Animal species MRLs substance(
33. s)2.3.1.1. Moxidectin Bovine, ovine 200 µ g/kg Moxidectin 20 µ g/kg 3. Agents acting on the nervous system Target tissues Fat Kidney, liver 16 [ S.L.449.19 MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS 3.1. Agents acting on the central nervous system 3.1.1. Butyrophenone tranquillizers Pharmacologically active Marker residue substance(
34. s)3.1.1.1. Azaperol Azaperone Animal species MRLs All food produc- 100 µ g/kg ing species 50 µ g/kg Target tissues Kidney Liver, muscle, fat 3.2. Agents acting on the automatic nervous system 3.2.1. ß 2sympathomimetic agents Pharmacologically active Marker residue substance(
35. s)3.2.1.1. Clenbuterol Clenbuterol hydrochloride 4. 4.1. Animal species MRLs 0,5 µ g/kg Bovine (Indication: 0,1 µ g/kg solely for tocoly- 0,05 µ g/kg sis in parturient cows) Equidae 0,5 µ g/kg 0,1 µ g/kg (Indications: tocolysis and the treatment of respiratory ailments) Target tissues Liver, kidney Muscle Milk Liver, kidney Muscle Corticoids Glucocorticoids Pharmacologically active Marker residue substance(
36. s)4.1.1. Dexamethasone Dexamethasone Animal species MRLs Bovine, porcine, 2.5 µ g/kg equidae 0,5 µ g/kg Bovine 0,3 µ g/kg Target tissues Liver Muscle, kidney Milk 5. Anti-inflammatory agents 5.1. Nonsteroidal anti-inflammatory agents 5.1.1. Arylpropionic acid derivative Pharmacologically active Marker residue substance(
37. s)5.1.1.1. Vedaprofen Vedaprofen 5.1.1.2. Carprofen Carprofen Animal species Equidae Bovine Equidae MRLs 100 µ g/kg 1000 µ g/kg 50 µ g/kg 1000 µ g/kg 500 µ g/kg 1000 µ g/kg 50 µ g/kg 100 µ g/kg Target tissues Liver Kidney Muscle Liver, kidney Muscle, fat Liver, kidney Muscle Fat MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS [ S.L.449.19 17 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 - pharmacological. 18 [ S.L.449.19 MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS 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. B) Residue documentation MAXIMUM RESIDUE LIMITS IN VETERINARY MEDICINAL PRODUCTS [ S.L.449.19 19 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.