Drugs are used widely in animal husbandry and the presence of drugs in foods like milk and meat is a health hazard according to international food and drug regulation rules. Worldwide consumption of antimicrobials in food animal production was estimated at 63151 (±1560) tons in 2010 out of which India shared 3 % and was ranked at 4th position. This is an indicator that how higher possibilities of drug accumulation within animal tissues (meat and milk) were becoming inevitable particularly in a rural Country like India where Food and Drug Regulatory rules regarding veterinary area are very poor. Food products can potentially be contaminated with hundreds of chemicals used in day to day life including pesticides, antibiotics, anthelmintics, hormones, heavy metals etc.
Antibiotics are widely used in veterinary practice which may appear as residues in foods like milk for certain period of time. Antibiotic residues in food have a harmful effect on health and lead to the development of antibiotic resistant. The use of drugs in veterinary practice has become a cause of public health concern as these residues may impose a health risk to consumers. The presence of drug residues in foods like milk and meat may be the result of various factors like failure to observe the withdrawl and withholding periods, extra label use of drugs, faulty or inappropriate dosage of drugs.
Lack of judicious and irrational approach of drug use in veterinary practice may lead to occurrence of drug residues in animal foods like milk and meat that finds entry into human food chain. The presence of antibiotic residues in milk causes interference in the manufacture of fermented dairy products. Milk and meat containing veterinary drugs above certain concentrations are dangerous. The maximum concentrations of drug residues have been set for different drugs so as to prevent harmful. It is becoming extremely difficult under rural conditions in India to observe withdrawl periods in respect of veterinary drugs administered for disease treatment.
Some of the most common drugs used in veterinary practice and their implications are briefed as follows:
Tetracyclines
Tetracyclines are broad spectrum antibiotics widely used in animal husbandry and poultry for prevention, control and treatment of infections. They are amphoteric in nature and always carry a charge and can achieve a neutral state as zwitterions. As a result they are highly polar molecules soluble in polar organic solvents and acidic/basic solutions. Tetracyclines are difficult to detect and quantify due to their instability, their capacity to form chelating complexes with multivalent cations (metal ions), their ability to bind with proteins and their capacity to react with charged silanol groups on silica based sorbents.
The long acting oxytetracycline used in food animals have long effect due to high dosage and prolonged persistence at the site of injection as a result of tissue irritation. Tetracyclines cross the placental barrier and enter the fetal circulation and they are also secreted in milk of lactating animals. Tetracyclines are generally nontoxic but they can cause large number of side effects. Tetracyclines are contraindicated in children up to age of 8 years and pregnant women because of risk of developing tooth discoloration. Other chronic effects include nephrotoxicity, hepatotoxicity, skin hyperpigmentation and hypersensitivity reactions. Tetracyclines have also been reported to cause hypokalemia, proximal and distal tubular acidosis. Persistent smaller levels of tetracyclines entering animal tissues of human food chain can lead to the development of tetracycline resistant human bacterial strains.
Enrofloxacin
Enrofloxacin rules the veterinary medical practice because of its high therapeutic significance in terms of bactericidal nature. It is a floroquinolone drug related to nalidixic acid. Enrofloxacin has carboxyl group in its structure and is amphoteric in nature thus HPLC detection would lead to tailing peaks. Enrofloxacin is a second generation floroquinolone and is a significant drug because of its strength and spectrum of antimicrobial activity so is widely used for animal treatment. The presence of drug residues in foods may be directly neurotoxic for newly borne animals and humans consuming meat and milk of under treatment animals or act as a source of resistant human pathogens.
Ceftriaxone
Ceftriaxone is a third generation, semisynthetic cephalosporin antibiotic. Cephalosporins are commonly used in veterinary medicine due to broad spectrum activity as compared to natural pecillins. Cephalosporin antibiotic contamination has a strong negative impact on human health and ecosystem as its residues contain toxic substances. The bactericidal activity of ceftriaxone results from inhibition of cell wall synthesis. Ceftriaxone has a maximum residue level (MRL) of 0.1 ppm (about 100µg/L) in milk, according to European Commission regulation. Antibiotic residues in milk and milk products exceeding MRL cause serious health concerns for consumers.
Anthelmintics (Ivermectin and Fenbendazole)
Ivermectin is a potent antiparasitic agent obtained from naturally occurring fermentation products. Ivermectin is a member of a group of naturally occurring macrocyclic lactones called avermectins. Tissue distribution of ivermectin residues in cattle and sheep have been studied. Although ivermectin has a broad safety range in anthelmintic treatment some of its excretion occurs through the mammary gland. The occurrence of ivermectin residues in foods may produce mutagenic effects in some mammalian species. The Codex alimentarius/European Union has set the residue limit of ivermectin in milk at 10µg/L (FAO/WHO, 1993). Fenbendazole belonging to benzimidazole group of anthelmintics are commonly used in veterinary industry.
Drug Residues in Poultry
Poultry farming holds significant importance in the Union Territory of Jammu and Kashmir, constituting a crucial agricultural activity. India is globally ranked third in egg production and fifth in poultry production, with the poultry sector’s estimated value standing at around Rs. 80,000 crore. The majority of sales in the poultry sector, approximately 90–95%, are attributed to live market sales of broiler meat, with processed chicken meat making up only about 5% of the total production. In terms of protein contribution per unit of human intake, affordable poultry meat and eggs surpass cow milk, mutton, pork, and beef.
Predictions indicate that by 2025, poultry products will become the most consumed animal protein items. Poultry farming, a facet of animal husbandry, involves raising domesticated birds like chickens, ducks, turkeys, and geese to produce meat and eggs for human consumption. The Union Territory of Jammu and Kashmir has witnessed notable progress in poultry farming, with production increasing from 5.6 million in 2003 (Livestock Census, 2007-2008) to 8.51 million in 2019 (Livestock Census, 2019). This substantial growth is attributed primarily to the adoption of enhanced breeding methods, improved nutrition, better management practices, and health coverage programs in recent years.
Under contemporary farming methods, broiler chickens are typically raised for a period of less than six weeks before being processed for meat. Free-range chickens, with a longer lifespan of approximately 8 weeks, are slaughtered later, while organic chickens are raised for about 12 weeks. Chickens specifically bred for egg production are commonly known as egg-laying hens or layers.
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The global commercial poultry industry is highly developed and serves as the primary source of animal protein in the form of meat and eggs. Poultry meat has become a viable alternative to beef and mutton, with particular importance in developing nations where poultry farming is cost-effective and can be carried out in small spaces, providing both protein and supplementary income for families. However, due to a lack of bio-security measures, the prevalence of infectious diseases, and the consequent indiscriminate use of drugs without adhering to withdrawal periods, poultry products have become potentially unsafe for human consumption.
Serendipitously, it was discovered that the by-products of antibiotic production, specifically the dried Sreptomyces aureofaciens both, contained high levels of vitamin B12, leading to increased growth in poultry animals when consumed. Subsequently, it was determined that trace amounts of antibiotics remaining in these by-products were responsible for this growth. As a result, antibiotics have been extensively employed in poultry farming to boost production. However, the widespread use of antibiotics in food animals poses a significant risk to humans due to the development of antibiotic resistance. This practice is linked to the emergence of antibiotic-resistant bacteria in animals, which can subsequently transmit to humans through food consumption, environmental exposure, and direct contact with contaminated meat.
Residues of antimicrobial compounds are also detected in animal-derived food products due to the improper or excessive use of these substances. These residues can be transferred to humans through food consumption and environmental exposure. To mitigate the presence of antibiotic residues in food and animal-derived products, regulatory agencies establish withdrawal periods, which represent the time between the last antibiotic dose given to food animals and the consumption of these animals or their products. Information about the use of antibiotics must be indicated on the labels of products intended for animal use.
Antibiotics have played a crucial role in treating bacterial infections, with the discovery of penicillin representing a significant milestone. About 80% of all food-producing animals undergo medication for a considerable portion of their lives. However, the excessive use and inappropriate application of antibiotics, fueled by a predominant emphasis on curative rather than preventive medicine, have given rise to bacterial resistance. Additionally, several antibiotics can elicit allergic reactions in sensitive individuals. This resistance poses a considerable challenge in contemporary medicine.
Usage of Antibiotics in Poultry Farming
Antibiotics serve various purposes in poultry farming:
- Therapeutic Use: Antibiotics are utilized for treating diseases in infected animals, involving the administration of antibiotics at high doses for a relatively brief period.
- Prophylactic Use: Antibiotics are employed to prevent diseases, usually through sub-therapeutic doses given to animals in their feed or drinking water when there are suspicions of infection, even in the absence of visible symptoms. These antibiotics are regularly administered throughout the broiler chicken’s life cycle.
- Growth Promotion: Certain antibiotics are used to boost the growth rate and productivity of poultry. This practice entails administering very low doses of antibiotics consistently throughout the lifetime of food-producing animals, typically through their feed. It is important to note that this varies from therapeutic and prophylactic antibiotic use, which involves higher doses administered through water. Antibiotic growth promoters are recognized for reducing gut bacteria, enabling chickens to absorb more nutrients for increased weight gain.
Studies indicate that the advantages of growth promoters are most evident in unhealthy animals or those housed in crowded and unsanitary conditions. Veterinarians and poultry producers often utilize sub-therapeutic levels of antibiotics to promote growth, enhance feed efficiency, and reduce the occurrence and severity of various poultry diseases. This approach has facilitated the efficient production of poultry products, ensuring the availability of high-quality meat and eggs to consumers at affordable prices.
However, the indiscriminate and careless application of antibiotics in poultry production can result in the presence of antibiotic residues in poultry tissues. This problem is exacerbated by factors such as incorrect dosage, improper administration methods, failure to adhere to recommended withdrawal periods, misuse of licensed products, illegal use of unlicensed substances, the utilization of extra-label dosages, and the use of drugs not approved for specific species. The detected residues include not only the original antibiotic compounds but also their isomers, metabolites, and associated impurities of veterinary drugs.
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Residue refers to substances with pharmacological action, conversion products, or other substances that may transfer to animal products and potentially endanger human health. Residues can persist in animal tissues for varying durations, depending on the antibiotic’s chemical structure, metabolism, and elimination route. A survey in the U.S. revealed that the most common antibiotic residues in carcasses were penicillins, streptomycin, oxytetracyclines, sulphamethazine, tetracycline, gentamicin, and neomycin.
The drug residues in livestock products not only cause the antimicrobial resistance and the emergence of superbugs, but also enter the food chain causing damage to aquatic species, soil microbes, human health and in the broader context it damages and endangers the ecosystems and the environmental health as a whole.
In the recent years the Division of Veterinary Medicine SKUAST Kashmir in Collaboration with the Department of Food Technology University of Kashmir has done some research on the detection and analysis of veterinary drug residues in livestock originated foods like milk, meat and chicken samples collected randomly from the market using the High Performance Liquid chromatography available at the department of Food Technology University of Kashmir, in which some drug residues have been detected but not up to the dangerous levels. However extensive and exhaustive studies are needed in this direction.
(The Author is Head, Veterinary Medicine, SKUAST Kashmir. Feedback: [email protected])
