ANTIMICROBIAL RESISTANT AND DRUG RESIDUES IN ANIMAL FOOD PRODUCTS: THREATS AND CHALLENGES

Introduction

Antimicrobial drugs are highly used to control diseases as it has to meet the world’s demand of milk, meat, milk-by product, meat-by product, wool and other animal by products, even more for providing adequate amountsto thegrowing world population. Medication improve weightgain, feed efficiency and cure the diseases infood producing animals. However, the productivity in terms of quality can not be obtain as there is a risk associated withresidues that remain in the tissues of treated animals at the timeof slaughter or residues in animal derived products like meat, milk,eggs and honey that poses a health hazard to the consumer. There are many factors influencing the occurrence of residuesin animal products such as drug’s properties and theirpharmacokinetic and dynamic characteristics, drug vehicle, physicochemical or biologicalreactions of animal body and processes on animal products.The most common reason are improper usage, extra-label or illegaldrug applications.People who are working in food industries and medical concern have drawn public attention to the threat of pesticides in the environment and in food. Use of diethylstilbestrol (DES), growth promoters, mal-injection of oxytocin, use of bovine somatotropin, pesticide added fodders for animal consumption are few examples of residual impact on consumers.
Antimicrobial residues in animal and its food product majorly leads to the antimicrobial drug resistant and it impact on the global health.

Factors affecting drug residues

It is one of the major problems for food contamination.

1)     Not following the recommended label instructions.

2)     Not following of recommended withdrawal times when antibiotic used.

3)     Administering too large volume at a single injection site may extend the drug release and metabolic time.

4)     Used to mix multiple drugs.

5)     Dosing, measuring, or mixing errors; allowing animals access to spilled chemicals or medicated feeds Animal effects- age, pregnancy, congenital, illness, allergies kind of animal factors.

6)     Chemical interactions between multiple drugs.

7)     Environmental contamination may alter.

8)     Improper use of agricultural chemicals such as pesticides, plant growth promoters which ultimately come into animal feed and then to the human.

Animal factors

a) Age and species of animal:

Weaning status and the age of the animal affect drug disposition. There is a probabiliy of species variation among animals in theirl ability to excrete drugs in the bile; example, chicken are good biliary excretes, whereas sheep and rabbit are characterized as moderate and poor excretes.

b) Disease status animal:

The disease perspective of an animal can also affect the pharmacokinetics of drugs which have administered, even it can influence the potential for residues. This can occur either when the disease affects the metabolic system (and consequently drug metabolism), or when the presence of infection and/or inflammation causes the drug to accumulate in affected tissues.

Extra-label drug use (ELU)

Extra-label Drug Use (ELU) refers to the use of an approved drug in a manner that is not in accordance with the approved label directions.ELU happen, when human practice drug used for animal.When a drug approved for one species of animal is used in another.When a drug is used to treat a condition for which it was not approved. The use of drugs at levels in excess of recommended dosages.Theuse of enrofloxacin solution as a topical ear medication (only approved for use as an injection) are the common ELU in veterinary medicine.

Improper withdrawal time

It is theinterval required from the time of drug administration to the required duration of time to excrete residues for safe food production before its slaughter. The withdrawal time (clearance period) is the time for the residue of drugs to reach at safe concentration as defined by the tolerance. Depending on the drug product, dosage form and route ofadministration, the withdrawal time may vary from a few hours to several days or weeks. Even different drugs have different biological and excretion activity that hampered the standard drug withdrawal time. Hence, improper withdrawal time is one the major concern for the presence of drug residue in animal food.

Effects of veterinary drug residues on public health

The major public health effects of drug residue are development of antimicrobial drug resistance, hypersensitivity reaction, carcinogenicity, mutagenicity, teratogenicity, Infertility, disability and disruption of intestinal normal flora. Ideally, the food product should not be consider for consumption until and unless there is complete elimination of residues. However, it can not be possible to determine. Hence, advancement of analytical equipment residues are denote as per the amounts present like parts per million (ppm), parts per billion (ppb) and parts per trillion (ppt) concentration.

Development of drug resistance

Resistant microorganism can come in contact easily  to human, either through direct contact or indirectly via milk, meat,egg and other by products. The use of antibiotic in livestock production has direct relation with the development of human antibiotic resistance. The animal fed with the lowprophylactic level of antibiotic may develop bacteria evolving resistance to this antibiotic during the preparation or consumption of food of animal origin. Human being obtains drug resistant bacteria such as Salmonella, Campylobacter, and Staphylococcus from food of animal origin. This is the major health concern. One cannot avoid food for survival, similarly one cannot avoid of getting bacteria by inhalation, ingestion or by contact. Hence, resistance is spreading very rapidly.

Drug hypersensitivity reaction

Allergic reactions to drugs may include anaphylaxis, serum sickness, cutaneous reaction, a delayed hypersensitivity response to drugs appear to be more commonly associated with the antibiotics, especially of penicillin (About 10% of the human population is hypersensitive), but in animals the extent of hypersensitive to the drug is not well known. Certain macrolides may also be responsible for liver injuries, caused by a specific allergic response to macrolide which hampered the hepatic cells.

Carcinogenic effect

The potential hazard of carcinogenic residues is relatedto their interaction or covalently binding to various intracellular components such as proteins, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), glycogen, phospholipids, and glutathione.

Mutagenic effect    

Several chemicals, including alkalizing agents and analogous of DNA bases, have been shown to elicit potenicial mutagenic activity. It has a potential hazard to the human population by production of gene mutagen or chromosome breakage that may have adversely affects human fertility.

Teratogenic effect

There are several drugs which are contraindicated in pregnancy like Benzimidazole is embryo toxic and teratogenic when given during early stage of pregnancy because of the anthelminthic activity of the drug. In addition to embryo toxicity including teratogenicity, the oxfendazole has also exhibited a mutagenic effect. When these drugs administered to the cow and without allowing its clearance time, if pregnant woman drink that cow’s milk, there is a more chances of occurrence of teratogenicity.

Safety evaluation for veterinary drug Residues Acceptable daily intake (ADI)

It is the amount of a substance that can be ingesteddaily over a lifetime without appreciable health risk. Calculation of ADI is based on an array of toxicological safety evaluation takes into acute and long-term exposure of the drug and its potential impact.

Maximum residue limit (MRL)

It is defined as the maximum concentration of any residue, resulting from the registered use of an agricultural or veterinary chemical, which is recommended to be legally permitted or recognized as acceptable in or on a food, agricultural commodity, or animal feed. The concentration is expressed in milligrams per kilogram of thecommodity (or milligrams per liter the case of a liquid commodity).

Detection methods

            There are different methods to detect drug residues like, liver enzyme digestion test, identification of chemical bond and structure of chemical, Tissue extraction methods, Analytical methods, Gas liquid chromatography (GLC), HPLC, Fluorescence analysis method, Marker residue detection method.

Measure to prevent residues

Most pharmacokinetic parameters have been determined in healthy animals. Yet diseased animals might have altered physiology. This may result in increased elimination a half-life by a factor of six or more or less. Doubling dose of the drug should only prolong the approved withdrawal time by one half-life; however, doubling the half-life as a result of the disease might do the double the necessary withdrawal time pathophysiologic states. Hence, It must be required intensive study on diseased model of animal.

The residue can be prevented by following measures:

• Farm herd management must be follow. All food animals should be maintained in a clean and healthy environment and clean milk production strategy must be follow.

• Must give attention to withdrawal times, advice to farmer for withdrawal.

• Carefully read all instruction and then only administer the drug properly.

• VeterinaryAyurveda and homeopathic approach may helpful.

• Ethno-veterinary practices may be recommended and promoted to practice.

• Development of simple and economic field test to identify drug residues in edible animal products should required.

• Rapid screening procedures for the analysis of antibiotic residues and instant grading and prohibition of food containing antibiotics must be follow.

• Make individuals and organizations aware of the problem through education by veterinary personnel, organizations, and literatures and governmental agencies.

• Prevent careless use of pesticides and insecticides, as well as cleansing and sanitizing agents.

• Do not give overdose from recommended levels and do not combine several antibiotics.

• Keep record of all treatments, including date of treatment, diagnosis, dosage of treatment.

• Keep record of treated animals.

• Prevent extra-label drug use.

Conclusion

Use of antimicrobial drugs in food-producing animals have the risk factor to retain their residues in animal, by product and their derived products. Which is the health hazard to the consumers. The most prone reason for this, are improper management in treatments, improper usage, overdose, use of long acting medication and failure by farmers to withdraw the milk for the particular time period. As the pharma giants are launching their newer products day by day, there is limited information particularly veterinary drug residue. Therefore, research area should be focus to generate data regarding the residual time- period. Strict withdrawal time should be practiced. Farmers and Veterinarian can be trained as a step guard to prevent the residue hazards.