Veterinary Drug Residues & Associated Health Hazard

Introduction

The use of veterinary drugs in livestock production is unavoidable as they are necessarily required to prevent or treat a disease. These substances are applied & administered to several animals including the food animals such as meat or milk-producing animals, poultry, fish, etc. to cure the disease (therapeutic use), to prevent the occurrence of the disease (prophylactic use), to improve the rate of weight gain and to improve feed efficiency thereby increasing production. The use of veterinary drugs such as antimicrobials, growth promoters, antiparasitics, etc. in food animals, can however lead to human health problems. It has been reported that if the veterinary drugs are used in large amounts and consistently, it could result in the deposition of antimicrobial residues in the muscle and organs of the animal.  Antimicrobial residues are pharmacologically active substances and their metabolites, which remain in foodstuffs obtained from animals to which the veterinary drug in question has been administered. Consumption of these residues in animal products may cause health risks to consumers including the development of antibiotic resistance and hypersensitivity reaction.

Status of antimicrobial consumption

The global average annual consumption of antimicrobials per kilogram of animal produced at present is estimated to be >100 mg/kg. India is a hot spot concerning antibiotic use and the present usage for animal production is estimated to be 30 kg/km², which is expected to grow 312% by 2030. It has also been observed that global consumption of antibiotics in animals exceeds the total antibiotic usage in human medical care. The global consumption of antimicrobials by livestock is predicted to increase by 67% from 63,151 tons in 2010 to 105,596 tons by 2030. FAO/WHO reported that antimicrobial residues in edible animal products have grown beyond permissible level particularly in developing countries. To curtail this, it is important to adhere to the maximum residue limits for veterinary drug residues in different animal food products set by the Food Safety & Standards Authority of India (FSSAI). Additionally, it’s imperative to analyze the animal products to ensure that residues do not exceed maximum residue limits.

Drivers of drug residues in animal products

There are certain factors that aid in the development of drug residues in food-producing animals. Livestock sector is growing at a very fast pace in most countries of the world. However, the growth of this sector is retarded by the introduction of different diseases caused by infectious microorganisms globally. The diseased and untreated animals eventually add to the economic burden of farmers since they grow very slowly and in the worst-case scenario, the disease may be fatal. This necessitates the use of antimicrobial drugs and growth promoters to protect and maintain the health of the animal. Another thing that has escalated the use of antimicrobials is the expanding human population which has resulted in increasing meat demand and consumption. In order to produce sufficient meat to fulfill the increasing demand, antimicrobials are being frequently used for the treatment of livestock diseases and to increase productivity.

Besides this, other factors that could be responsible for drug residues in animal products include extra-label drug usage (ELDU) and failure to comply with antimicrobial withdrawal periods. Extra-label drug use (ELDU) refers to the use of an approved drug in a manner that is not as per the approved label directions. This includes administration of a different dose, administration of a different volume per injection site, administration to a different species, administration via a different route, administration at a different interval, administration for a different duration, and administration for a different indication than listed on the label. The withdrawal period is the interval necessary between the last administration of the drug to the animals under normal conditions of use and the time when the treated animal can be slaughtered or marketed for safe consumption of the product. Failure to comply with the antimicrobial withdrawal period could create low therapeutic doses and a high concentration of antimicrobial residues in meat products.

Potential effects of veterinary drug residues on human health

1. Development of drug resistance

Many antimicrobials that are used in livestock are closely related to those used in humans. Injudicious use of antimicrobials in livestock can lead to the development of antimicrobial resistance in animals and the growth of resistant bacteria in different animal tissues, which can then be transmitted to humans either through direct contact or via milk, meat, egg, and other animal products.

2. Drug allergy or hypersensitivity reactions

It is defined as an immune-mediated response to a chemical agent that can develop in a sensitized patient and such allergic reactions are usually mediated by IgE. Drug allergy can manifest as cutaneous reactions like angioedema, skin rash or can take severe forms like anaphylaxis, serum sickness etc. For instance, if meat products having penicillin residues are consumed by humans which are allergic to penicillin, there are chances of them developing allergic reactions.

3. Carcinogenic effect

The term carcinogenic refers to any substance or an agent that is capable of altering the genetic makeup of an organism and promoting the formation of cancer. Carcinogenic residues impart danger to human health by covalently binding intracellular components including DNA, RNA, proteins, etc. Earlier Diethylstilbestrol (DES), an hormone-like compound was used for food producing animals, but it was later banned owing to its strong carcinogenic effect.

4. Mutagenic effect

Mutagen refers to any physical or chemical substance which is capable of causing mutations in a DNA molecule thereby altering the genetic makeup of a cell or organism. Studies have shown that certain alkalinizing agents which are used to manage disorders associated with low pH are mutagenic.

5. Teratogenic effect

The term teratogen applies to drug or chemical agent that produces a toxic effect and alters the structural and functional integrity of the developing embryo/ fetus during a critical phase of gestation. Studies have revealed that benzimidazole which is an anthelmintic is not only mutagenic but also embryo toxic and teratogenic when given during early stage of pregnancy.

6. Disruptions of normal intestinal flora

The intestinal microflora refers to the bacteria that usually live in the intestine. These establish control and act as a barrier preventing the incoming pathogen from getting colonized in the gastrointestinal tract and causing diseases. However studies have shown that antibiotics or other antimicrobials administered for therapeutic purposes may reduce the total number of the bacteria or selectively kill some important species. This results in alteration of the ecological composition of intestinal microflora as a consequence of which gastrointestinal disturbances occur.

Control & Preventive measures to reduce veterinary drug residues

• Drug residues are best avoided by implementing hygienic practices during animal rearing and avoiding unwanted use of antibiotics.
• Setting up of tolerance limits and their enforcement by regulatory bodies.
• Strict adherence to withdrawal periods to render meat safe for human consumption.
• Only drugs approved in food animals should be used as unapproved drugs have no data regarding efficacy, safety, or withholding time.
• Creating awareness of proper drug use among producers and general public by dissemination of information.
• Reducing antibiotics usage in food animal rearing (Many developed countries have banned its use as growth promoters).
• Switching to alternatives of antibiotics like bio control measures and ethno-veterinary practices (use of herbal plants).
• Screening methods should be developed for rapid detection and segregation of samples containing residues above the limit.
• Proper processing techniques should be used to inactivate the antibiotic residue, e.g. refrigeration causes inactivation of penicillin, different cooking conditions (temperature and time) and fermentation can contribute to a marked decrease in concentration.
• Activated charcoal, resins and UV irradiation can also help to inactivate residues.

Need of the hour

It’s important for every veterinarian to pay sufficient attention to ensure that only approved drugs are used for treating animals, to avoid ELDU and to adhere strictly to the withdrawal period for products like milk, meat etc. derived from animals treated with different drugs. To deal with the problem of drug residues, coordination from the regulatory bodies is also required to monitor the use of antimicrobial drugs to control diseases and also enforce punishment on indiscriminate usage. Additionally development of sensitive, selective and reliable analytical methods should be encouraged to easily detect and monitor antimicrobial residues in animal products.

References

1. Falowo, A. B., & Akimoladun, O. F. (2019). Veterinary Drug Residues in Meat and Meat Products: Occurrence, Detection and Implications. In Veterinary Medicine and Pharmaceuticals. IntechOpen.
2. Rana, M. S., Lee, S. Y., Kang, H. J., & Hur, S. J. (2019). Reducing veterinary drug residues in animal products: A review. Food science of animal resources, 39(5), 687.
3. Vishnuraj, M. R., Kandeepan, G., Rao, K. H., Chand, S., & Kumbhar, V. (2016). Occurrence, public health hazards and detection methods of antibiotic residues in foods of animal origin: A comprehensive review. Cogent Food & Agriculture, 2(1), 1235458.
4. Beyene, T. (2016). Veterinary drug residues in food-animal products: its risk factors and potential effects on public health. J Vet Sci Technol, 7(1), 1-7.
5. Van Boeckel, T. P., Brower, C., Gilbert, M., Grenfell, B. T., Levin, S. A., Robinson, T. P. & Laxminarayan, R. (2015). Global trends in antimicrobial use in food animals. Proceedings of the National Academy of Sciences, 112(18), 5649-5654.