Analysis Of Tetracycline Residues In Poultry And The Impact Of Its Wash - Off On Macrobrachium Rosenbergii Bijargi

Title : Analysis of tetracycline residues in poultry and the impact of its wash-off on Macrobrachium rosenbergii Name of the student : Bijargi Shriharsh Rameshwar Chairman : Dr.P. Hariharan, Ph.D Professor & Head, Department of Veterinary Pharmacology & Toxicology, Madras Veterinary College, Chennai -600 007 Year : 2012 Degree : Doctor of Philosophy in Veterinary Pharmacology and Toxicology University : Tamilnadu Veterinary and Animal Sciences University Antimicrobials are commonly used in animal production since 1940’s, after it was observed that tetracycline increased the survivability and growth rate in chicken. With the intensification of broiler industry, stress on birds increased and hence the use of antimicrobials in production has also increased. To safeguard public health against the deleterious effects of antimicrobial residues in consumable meat, regulatory agencies all over the world have come up with measures like prescribing “Maximum Residue Limits” (MRLs) so as to keep the antimicrobial concentration in meat below the prescribed limit by following strict withdrawal periods. Considering the utility and requirement regarding the use of tetracyclines in mass medication through drinking water and the lack of published data in this regard, the present study was designed and conducted on pharmacokinetic and tissue residue analysis of oxytetracycline (10 mg.kg-1), doxycycline (20 mg.kg-1) and tigecycline (10 mg.kg-1) in broilers. Twelve pharmacokinetic studies (Intravenous – single dose, oral– single dose, through drinking water– single dose, through drinking water– multiple doses) and three tissue depletion studies including six sacrifices per study at seven day interval till 35 days post-treatment were conducted. Residues of tetracyclines were analysed in muscle, liver and kidney considering Codex MRLs. An attempt was also made to study the effect of tetracyclines on aquatic invertebrates when these antimicrobials are present in poultry unit waste (wash-off) using Macrobrachium rosenbergii as a model for the toxicity study. Oxytetracycline demonstrated very poor bioavailability through oral (23.52%) and drinking water route (2.43 and 4.81% for single and multiple dose). In tissue depletion study, muscle tissues was observed to retain oxytetracycline for longer period than other tissues with the levels above MRL at day 7 while liver and kidney had quantifiable levels only on day 1. An overall withdrawal period of 14 days can be suggested for oxytetracycline at the given dosage regimen. Doxycycline was found to have greater stability and fair systemic bioavailability after administration through drinking water (27.60 –single dose and 33.28% multiple dose) or per-os route (47.60%). A consolidated withdrawal period upto 28 days can be prescribed for doxycycline based on tissue depletion studies. Tigecycline, a novel glycylcycline compound also had poor bioavailability (through drinking water after 5 doses – 2.2%) similar to oxytetracycline. The tissue depletion study revealed presence of quantifiable tigecycline only on day 1 of sacrifice, suggesting a necessary withdrawal period upto 7 days in all the tissues. Oxytetracycline and tigecycline could not meet the therapeutic levels in plasma required for treatment of systemic infections. Doxycycline, though found to be most feasible tetracycline for mass medication, exhibited a longer withdrawal period required to bring the tissue concentrations below prescribed limits, which questions the field applicability of this antimicrobial at given dose and dose interval. Usefulness of oxytetracycline and tigecycline for treatment of gastrointestinal infections and as a growth promoter can be considered since these tetracyclines have lower tissue penetration and shorter withdrawal period. While evaluating the effect of tetracyclines as wash-off contaminants from poultry farm the concentrations of tetracyclines as high as 0.5mg/g of wash-off was observed. On testing Macrobrachium rosenbergii (Giant freshwater prawn) for acute immobility test with the same amount of tetracyclines for 48 h, no acute toxicity was evident. However, delay in hemolymph clotting time and molting time suggested possible immunosuppression caused by tetracyclines.