Yusuf, Kedir, Abrahim, Ibsa: Review on the impacts of drug residue in animal products on human health issues
ABSTRACT
The use of veterinary drugs in food-producing animals may result in drug residues in foodstuffs such as meat, milk, eggs, or honey. A high degree of antibiotic residue consumption from animal products to humans might affect immunological reactions and can unfavorably influence digestive microbiota in susceptible people. Antimicrobials also known as antibiotics, anti-infectives, antibacterials, or chemotherapeutics, include synthetic and natural compounds. The introduction of antibiotics to the veterinary field started soon after the use of antibiotics for the treatment of bacterial diseases in humans. Detection of drug residues from tissues and other animal products could be quite an expensive, time-consuming, and laborious venture. To determine the withdrawal period, regulatory authorities must employ a scientific process that includes establishing the maximum residue limit for that medicine. The growing use of antimicrobials to prevent and treat diseases increases the probability of residues of these substances in products obtained from animals. Resistant microorganisms can get access to humans, either through direct contact or indirectly via milk, meat, and/or eggs. The ongoing threat of antibiotic contamination is one of the biggest challenges to public health that is faced not only by the African people but also by the human population worldwide. Globally, more than half of all medicines are prescribed, dispensed, or sold improperly. The first step in residue prevention is to make individuals and organizations aware of the problem through education through scientific literature, computer databases, veterinary consultations, and the efforts of national organizations.
KEYWORDS Animal products; antimicrobials; drug residue; withdrawal period
Introduction
Veterinary anti-infection agents are mainly used by cattle and poultry farmers, which might prompt antibiotic residues from food animals to humans, and consequently cause dangerous health hazards to the consumers [ 1]. The presence of antibiotic residues in foodstuffs can present risks to human well-being, e.g., sensitivity to antibiotics, allergy responses, microflora imbalance, bacterial resistance to antibiotics in microorganisms, and loss to the food business [ 2]. The use of veterinary drugs in livestock production is inevitable as they are essential for therapeutic and prophylaxis, modification of physiological functions (such as tranquilizers and anesthetic drugs), improvement of growth, and productivity as well as ensuring food safety [ 3].
The high degree of antibiotic residues consumed from animal products to humans might affect immunological reactions and can unfavorably influence digestive microbiota in susceptible people [ 4]. Rationally, there is no product coming from a treated animal should be consumed unless the entire drug administered has been eliminated. This is called zero tolerance, where the concept is in fact equivalent to the idea of the total absence of residual amounts [ 5]. The European Food Safety Authority has recently issued an opinion on the effect of residues in meat and reflected that epidemiological data provided evidence for an association between some forms of residue-dependent cancers and meat consumption [ 6]. Other drug residue problems are the development of antibiotic-resistant microbes and drug misuse [ 7].
Therefore, veterinary drug residues have been considered a global food contamination challenge [ 8]. These residues may result from inappropriate or extra-label drug usage, failure to maintain drug withdrawal periods or poor livestock production practices [ 9]. In general, the health effects of drug and chemical residue includes acting as a mutagen, carcinogenic, and teratogenic agent and reduction in reproductive performance, drug allergy, and acute toxicity in human [ 10]. This is because the metabolism of some drugs may be rapid and efficient. However, others metabolized slowly and poorly and accumulated in the edible portion of the animal. Approximately 80% of food animals receive antibiotics for part or most of their life [ 11]. Afterward, consumers can easily be exposed to residues, resulting in health hazards [ 12]. The presence of unexpected residues in foodstuffs, such as meat, milk, and eggs, may be attributable to unintentional or cross-contaminated feed in the pasture or feed mills, recirculation through manure and bedding materials, and antimicrobial-contaminated feed ingredients or water provided to the animal [ 13]. Hence, due to their extensive use, a residue source is often found in animal products such as meat, milk, and eggs [ 13].
The problems raised due to drug residue in animal products cause economic loss and health impacts through antimicrobial resistance (AMR). So, awareness creation for the community by veterinarians and para-veterinarians must be needed through a recommendation when treating animals the community does not use animal products before drug withdrawal periods are finished.
Therefore, the objective of this seminar paper is detailed further. Drug residue in animal products is nowadays known as the most frightening condition in the continent with increasing veterinary paraprofessional, but the least possible professional practices.
- To review the potential cause of veterinary drug residue and its public health impact.
- To highlight prevention and control measures of drug residues in food-producing animals.
Literature Review
Review on antibiotic residue sources in animal products
Antimicrobials also known as antibiotics, anti- infectives, anti-bacterial, or chemotherapeutics, include synthetic and natural compounds with low molecular weight produced by fungi and bacteria. They are widely used to control, prevent, and treat infection, and to enhance animal growth and feed efficiency [ 14]. Antimicrobials are classified according to their chemical structure. Each class is characterized by a typical core structure and the various members of the class are differentiated by the addition or removal of secondary chemical structures from the core structure [ 13]. The most commonly used antimicrobials in food-producing animals are ß-lactams, tetracycline, aminoglycosides, lincosamides, macrolides, pleuromutilins, and sulfonamides. They were administered to animals by injections, orally in feed or water, topically on the skin, and by intramammary and intrauterine infusions [ 15]. Subcutaneous and intramuscular administrations increase the potential for residues at the injection sites [ 16, 17].
Almost 90% of all antibiotics used in farm animals and poultry are reported to be administered at sub-therapeutic concentrations. About 70% of this is for disease prevention and 30% are for growth promotion. The risk of residue from the milk is higher in developing countries compared to developed ones. This might be related to a lack of facilities for detection and regulatory bodies that control the drug residue level in foods in the form of maximum residue limits (MRLs) [ 18]. The major causes of drug residue accumulation in food-producing animals include improper observation of withdrawal periods, failure to maintain treatment records, overdose, or use of prohibited drugs for economic animal treatment [ 19]. Contaminated animal feedstuffs also act as an important source of drug residues [ 20].
Manifestation of antibiotic residues in animal’s product
The introduction of antibiotics to the veterinary field started soon after the use of antibiotics for the treatment of bacterial diseases in humans. The main use of antibiotics in animal rearing was for the treatment and prevention of diseases. Indeed, antibiotics have been used for the treatment of mastitis, arthritis, respiratory diseases, gastrointestinal infections, and other infectious bacterial diseases [ 33]. More recently antibiotics have been used for improved growth, especially in broilers and feed lot animals, antibiotics improve growth rate by thinning mucous membranes in the gut; altering gut motility which enhances assimilation production of favorable conditions for beneficial gut microbes (by destroying harmful bacteria); and partitioning of proteins for muscle growth via cytokine suppression. Antibiotics also favor growth by decreasing the activity of the immune system, reducing the waste of nutrients, and reducing toxin formation [ 34]. Most of these drugs are administered by the farmers themselves fuelled by the availability of veterinary medicine to the public with or without veterinary prescription [ 35].
Furthermore, inappropriate use of veterinary drugs in dairy animals without considering the withholding periods causes drug residues in milk. Apart from these, contaminants are also introduced during milk collection, preservation, transport, processing, and packaging [ 36]. Similarly, improper milking or milk collection, insufficient cleaning, and poor hygienic conditions, i.e., overall inappropriate management practices also contribute to contamination of milk by drugs and chemicals [ 37, 38]. Therefore, milk could be a potential source of drug residues and contaminants in the human diet [ 39].
When drugs are administered to laying hens, their metabolites may accumulate as residues in egg components (yolk and albumen) [ 8]. These drugs are absorbed in the intestine, carried through blood/plasma to the ovary, and deposited in the inner yolk to the magnum of the oviduct for accumulation in the albumen, uterus, and the oviduct; and finally, during plumping of the eggs, drug residues accumulated in the eggs [ 40]. Raw eggs are usually not consumed, unless refrigerated and subjected to heat. Heat treatment promotes dehydration, protein denaturation, and pH changes that can help reduce residue quantity, and chemical formulation, as well as alter residue solubility [ 41].
Screening methods of residue detection in animal product
Screening of food products from animal origin for the presence of antimicrobial residues started soon after the introduction of antibacterial therapy in veterinary medicine. Initially, it mainly concerned process monitoring in the dairy industry to prevent problems in fermentative dairy production, but from the early 1970s regulatory residue screening in slaughter animals also became more commonly introduced. An efficient screening method needs to be low-cost and high-throughput, able to effectively identify potential noncompliant samples from a large set of negative samples [ 42]. Screening methods are usually inexpensive, easy to use and handle, rapid, suitable for high-throughput analysis, and have good sensitivity, specificity, and detection capability (ccβ) with a probability of error of p < 5%. They usually do not provide unequivocal identification and usually do not result in exact quantitative results [ 43].
Detection of drug residues from tissues and other animal products could be quite an expensive, time-consuming, and laborious venture. Typically, muscle, liver, kidney, and fat are analyzed because they are the tissues that are typically eaten in large amounts, function as storage points for fat-soluble residues, or tissues that metabolize the major portion of the drug in the process of body elimination and can screen a large number of samples at minimal cost [ 44]. Veterinary drug residues in milk remain a paramount concern to farmers, processors, milk regulatory agencies, and consumers because milk is widely consumed by people of all ages [ 45]. The production of milk and milk products is linked to the environment which is somehow designed by human beings [ 39, 36]. Thus, contamination of milk starts right from the intake of contaminated pasture and drinking water by the animal [ 25, 26]. Various analytical methods are available for screening and confirmation of antibiotic residues in animal products. They are microbial inhibition tests, biosensors, enzyme linked immunosorbent assay (ELISA), high-performance liquid chromatography (HPLC), liquid chromatography with mass spectrometry, liquid chromatography-tandem mass spectrometry, and ultra-performance liquid chromatography- mass spectrometry widely used for confirmation and quantitative analysis of drug residues in milk, meat, and egg [ 46] ( Table 1).
Microbial inhibition test
Microbial inhibition assays are very cost-effective and they have the potential to cover the entire antibiotic spectrum within one test. There are two main test formats: the tube test and the (multi) plate test. A tube (or vial, or ampoule) test consists of a growth medium inoculated with (spores of) a sensitive test bacterium, supplemented with a pH or redox indicator. At the appropriate temperature, the bacteria start to grow and produce acid, which will cause a color change. The presence of antimicrobial residues will prevent or delay bacterial growth and, thus, is indicated by the absence or delay of the color change. This format is commonly applied in routine screening of milk, but it is also increasingly used for analysis of other matrices [ 42].
An important advantage, compared to immunoassays and instrumental methods, is that microbiological tests can detect any antibiotic compound that shows antibacterial activity. Moreover, they have the potential to cover the entire antibiotic spectrum within one test. The most important drawbacks of the microbiological tests are their lack of selectivity, especially the tube test, relatively high detection limits, and the long incubation time. As a result, microbiological inhibition assays are not suitable for the detection of banned antibiotic compounds like chloramphenicol (CAP) [ 43].
Enzyme linked immunosorbent assay
According to Samsidar et al. [ 47], introduced two forms ELISA: direct competitive (dc)-ELISA and indirect competitive (ic)-ELISA, of which the ic-ELISA method is more advanced. In the past decade, this reliable high-throughput immunoassay has been widely used to determine various veterinary drugs in animal-derived foods. The basic principle of ELISA is to combine a specific antigen–antibody immunological reaction with an enzymatic catalytic reaction and to display the primary immune response with amplification of the enzymatic reaction. ELISA is the most useful and specific test for screening drug residues in meat, milk, and eggs. The Competitive ELISA is commonly used for quantitative analysis of tetracycline, fluoroquinolones, and CAP in meat. the CAP residues in milk and chicken muscle. The sensitivity of CL-ELISA is 2–3 times higher than Competitive indirect chemiluminescent enzyme-linked immunoassay (CL-ELISA) is used to determine conventional ELISA and can detect trace amounts of CAP as low as 3.19 ng/kg in chicken muscle [ 46]. Tetracycline residues in milk were detected using a competitive ELISA, according to Gaurav et al. [ 48]. In various parts of Punjab, 133 samples of cattle milk were examined, and 18 of those samples had concentration tetracycline residues. Tetracycline residual levels in cattle milk samples were found to range from 16 to 134.5 µg/l. The maximum permitted tetracycline antibiotic residual levels (MRLs) were exceeded in three samples.
High-performance liquid chromatography
High-performance thin-layer chromatography (HPTLC) has been applied successfully for the qualitative and quantitative detection of multiresidues in food samples even though its use has rapidly decreased during the last decade. Visualization of the components can be performed either by spraying an appropriate chromogenic reagent or under UV light. Quantitative determination is possible through the relative intensity of the spot in the plate, which is measured against that of the internal standard by scanning densitometry. Recent developments similarly allow for the automation of HPLC with the appropriate equipment. HPTLC has been applied to different residues such as thyreostatic drugs, clenbuterol and other agonists, nitroimidazol, and sulfonamides in animal tissues. It has also been applied to the analysis of corticosteroids and antibiotics in milk. The spots can consist of the combination of thin-layer chromatography with microbiological detection directly on the plate resulting in enhanced sensitivity. It has been applied to the detection of flume-quine in milk. The choice of the detection system is very important for selectivity and sensitivity. Some analytes not detected by absorbance, refractive index, or fluorescence may require chemical modifications to render chromophore, fluorescent, or UV-absorbing compounds. Usually, the detection of multiresidues is based on a solid-phase extraction cleanup followed by filtration and injection into a reverse-phase HPLC with UV-diode array detection. It has been applied for the detection of antibiotics in meat, milk, and eggs. Methyl thiouracils in urine anabolic steroids in nutritional supplements and urine and corticosteroids like dexamethasone in water, feed, and meat [ 49].
Table 1.Common chemical and drug residues appear in the milk.
Class |
Drugs/chemicals |
References |
Antibiotics |
Penicillin, oxytetracycline, streptomycin, neomycin, tetracycline, sulfamethazine, gentamycin, enrofloxacin, azithromycin |
[21]; [15]; [22,23], |
Antihelminthics |
Closantel, ivermectin, levamisole, albendazole, |
[24] |
Pesticides |
Organochlorines, organophosphates, DDT, HCHs |
[25,26] |
Hormones |
Bovine somatotropin, progesterone, testosterone |
[27] |
Mycotoxins |
Aflatoxin M1, aflatoxin B1 |
[28] |
Nitrates and nitrites |
Nitrate fertilizers, rodenticides |
[22,29] |
Heavy metals |
Lead (Pb), cadmium (Cd) |
[30,31] |
Ethiopian analyses of kidneys with TLC showed that the majority of the samples have variable amounts of oxytetracycline residues. Out of the total 384 kidney samples analyzed using TLC in this study 274 (71.4%) had detectable levels for oxytetracycline residues. Tetracycline and doxycycline were not detected in any of the samples. In every sample where the kidney sample had been positive for oxytetracycline by TLC, muscle samples were also positive by HPLC. In Addis Ababa, Debre Zeit, and Nazareth slaughterhouses 120 (93.8%), 48 (37.5%), and 106 (82.81%) kidney and beef samples were positive for oxytetracycline, respectively [ 50].
In Iranian cattle tissue (triceps muscle, gluteal muscle, diaphragm, kidney, and liver) from the local market was examined for a tetracycline group of antibiotics (tetracycline, oxytetracycline, and chlortetracycline) by HPLC method. The tetracycline concentrations in the triceps muscle, gluteal muscle, diaphragm, kidney, and liver were 176.3, 405.3, 96.8, 672.4, and 651.3 ng/g, respectively. The concentrations of tetracyclines were higher in liver and kidney samples compared to other samples and it was higher in cured meat products [ 46].
Withdrawal periods and maximum residue limit
The use of animal medicines requires observance of the withdrawal period. This is the time between the last doses given to the animal and the time when the level of residues in the tissues (muscle, liver, kidney, skin, and fat) and products (milk, eggs, and honey) is lower than or equal to the MRL. Until the withdrawal period has elapsed, the animal or its products must not be used for human consumption [ 51]. The term maximum limit for residues of veterinary antibiotics or drugs is the maximum concentration of veterinary drug residues resulting from the use of veterinary drugs to be legally permitted or which is recognized as acceptable in animal food products. The concentration of drug residue can be expressed in milligrams/micrograms per kilogram of the commodity (or milligrams/micrograms per liter in the case of a liquid commodity) or ppm/ppb [ 18].
The MRLs are specified for several animal- derived food products (different edible tissues and other food commodities). When veterinary drugs are used according to the period of treatment and the withholding period specified before slaughter or milking, the concentration of drug residues should be at levels that will not cause adverse effects on the health of the consumer. Therefore, animals are suitable for food production if the amounts of veterinary antibiotic residues in animal food products are below levels that could cause a health risk for consumers [ 52]. Nowadays, regulatory bodies have been established for veterinary drugs used in food-producing animals for regular monitoring of veterinary drug residues in livestock products. The regulatory laws can help the government policies in managing animal-derived food safety, prevention, and control of food safety incidents [ 18] ( Table 2).
Table 2.Maximum antibiotic drug residue limits for commonly used antimicrobials in food staffs of animal derived.
Antimicrobial |
Muscle (µg/kg) |
Liver (µg/kg) |
Kidney (µg/kg) |
Fat (µg/kg) |
Cow milk (µg/l) |
Amoxicillin |
50 |
50 |
50 |
50 |
4 |
Benzyl penicillin |
50 |
50 |
50 |
50 |
- |
Chlortetracycline/oxytetracycline/tetracycline |
200 |
600 |
1,200 |
- |
100 |
Gentamycin |
100 |
2,000 |
5,000 |
100 |
200 |
Streptomycin/dihydrostreptomycin |
600 |
600 |
1,000 |
600 |
200 |
Erythromycin |
- |
- |
- |
- |
- |
Neomycin |
500 |
500 |
1,000 |
500 |
1,500 |
Sulfadimidine |
- |
- |
- |
- |
25 |
Tilmicosin |
100 |
1,000 |
300 |
100 |
- |
Tylosin |
100 |
100 |
100 |
100 |
- |
Risk factors for drug residue in animal product
The growing use of antimicrobials to prevent and treat diseases increases the probability of residues of these substances in products obtained from animals. The factors favoring the presence of antimicrobial residues in foods of animal origin include failure to comply with the waiting period after the administration of antimicrobials, failure to consult a veterinarian before using antimicrobials, and lack of prior training in animal husbandry. The waiting period is the period after the administration of a treatment, during which any food produced by the treated animal must not be marketed. The defined waiting period takes into account the pharmacokinetic variability between individual animals in the processes of absorption, distribution, metabolism, and excretion of residues (active ingredients and metabolites). These processes depend on the physiological condition of the animal and the genetic traits influencing metabolism or excretion. As these differences influence residue kinetics, an adjustment of the waiting period may be required when medicinal products are administered to animals. At this stage of development in veterinary drugs, such variations are not taken into account [ 54].
The incidence of veterinary antibiotic residues in animal-derived food poses a significant health risk to the health of consumers because of the emergence of microbial resistance noticed in recent years. Extensive use of antibiotics might increase the risk of an adverse effect of residues on the customer and the occurrence of antibiotic resistance as well as hypersensitivity reactions on consumers. Therefore, the ingenious use of veterinary antibiotics in the manner of preventing animal feed and food contamination is required [ 53].
Public health risks from vet drug residues are anaphylaxis/food allergies, reproductive disorders, e.g., birth malformation, genotoxicity, development of AMR through the food chain, and long-term effects, e.g., carcinogenesis. Risk factors responsible for the development of residue are the following, age of the animal, weaning status, and to a lesser extent, the age of the animal affects drug disposition. Feeding and diet can affect the bioavailability of drugs, disease status, and pharmacodynamic and pharmakokinetic nature of the drugs [ 55].
When performing hazard characterization of veterinary drug residues, sub-optimal toxicological or microbiological data can significantly impact the derivation of health-based guidance values (HBGVs). In some cases, a lack of critical toxicological or microbiological data makes completing the hazard characterization impossible, which precludes the remainder of the risk assessment (e.g., if no acceptable daily intake/acute reference dose can be established, MRL derivation cannot proceed). In some situations, hazard characterization challenges can be mitigated through a variety of strategies to facilitate HBGV derivation and continue the residue assessment. Such strategies may include using more conservative uncertainty (i.e., safety) factors, or using surrogate values based on thresholds of toxicological concern or quantitative structure-activity relationship models. However, the hazard characterization and residue assessment processes and strategies to address hazard characterization deficiencies may impact the residue assessment such as derivation of more conservative MRLs than necessary had a complete toxicological/microbiological data set been available [ 56].
Development of antimicrobial drug resistance
Human health can either be affected through residues of drugs in food of animal origin, which may cause direct side effects [ 57], or indirectly, through the selection of antibiotic resistance determinants that may spread human pathogens [ 58– 60]. Resistant microorganisms can get access to humans, either through direct contact [ 60] or indirectly via milk, meat, and/or eggs. Clearly, the use of antibiotics in livestock production has been associated with the development of human antibiotic resistance [ 59, 60]. It has been documented that humans develop drug-resistant bacteria, such as Salmonella, Campylobacter, and Staphylococcus, from food of animal origin [ 19].
Veterinary Drug Residue Incidence on Public Health
In many African countries including Ethiopia, antibiotics are used indiscriminately for the treatment of bacterial diseases or as feed additives for domestic animals and birds. The ongoing threat of antibiotic, contamination is one of the biggest challenges to public health that is faced not only by the African people but also by the human population worldwide. Such residues are spreading rapidly, irrespective of geographical, economic, or legal differences between countries [ 61].
A number of possible adverse health effects of veterinary drug residues have been suggested. The bacteria that usually live in the intestine act as a barrier to prevent incoming pathogenic bacteria from being established and causing disease. Antibiotics might reduce the total number of these bacteria or selectively kill some important species. Sensitive individuals may experience allergic reactions to antibiotic residues, particularly penicillin residues, in meat. Estimates of the prevalence of drug sensitivity vary but are estimated to be about 7% in the general population. However, not all of these people experience severe symptoms, and residue levels detected in meat are likely to be below the threshold that would induce a hypersensitive response. The broad-spectrum antibiotics may adversely affect a wide range of intestinal flora and consequently cause gastrointestinal disturbance [ 49].
The drugs, such as tetracycline, furazolidone, tamoxifen, phenobarbital, and Dichlorodiphenyltrichloroethane (DDT), act as a carcinogen and produce various types of cancers. Furthermore, nitrofurans can react with nitrite to yield carcinogenic metabolite nitrosamines. Hence, the United States Food and Drug Administration [ 62] has banned furazolidone and its metabolites. Some of the drugs have the potential to cause deoxyribonucleic acid mutation or chromosomal damage subsequently leading to infertility in human beings [ 38]. Other literature data indicates bone marrow depression, hepatic disorders, reproductive disorders, and myelotoxicity [ 63]. Developmental toxicity, embryotoxicity, or teratogenic effects are reported due to the exposure of some pharmaceuticals during pregnancy. The teratogenic drugs include some chemotherapeutic agents (thalidomide), anithelminthics (albendazole), antibiotics (tetracyclines and aminoglycosides), antiepileptics (carbamazepine), hormones (diethylstilbestrol and misoprostol), and other drugs such as angiotensin-converting enzyme inhibitors, cyclophosphamide, and methimazole [ 64, 13]. Granowitz and Brown [ 65] reported aplastic anemia caused by antibiotic residues (CAP) in milk.
Extent of Drug Residue on Animal Products in Ethiopia
Globally, more than half of all medicines are prescribed, dispensed, or sold improperly. This is more wasteful, expensive, and dangerous, both to the health of the individual patient and to the population as a whole magnifies the problem of misuse of anthelmintic agents [ 66]. In many African countries, antibiotics may be used indiscriminately for the treatment of bacterial diseases or they may be used as feed additives for domestic animals and birds [ 67]. The ongoing threat of antibiotic contamination is one of the biggest challenges to public health that is faced by the human population worldwide [ 68]. Ture et al. [ 42] reported that in Ethiopia, as the study conducted from March 2016 to June 2016 at the University of Gondar veterinary clinic revealed, anthelmintic drugs are quite commonly but improperly utilized in the clinic.
Three groups of anthelmintics namely benzimidazoles (albendazole, fenbendazole, mebendazole, and triclabendazole), imidazothiazole (tetramisole and levamisole), and macrocycl lactone (Ivermectin) were used. Utilization of a limited group of drugs for a long period may favor the development of resistance which is a risk factor for drug residues [ 69]. Though the primary purpose of veterinary drugs is to safeguard the health and welfare of animals [ 70], 44.3% of anthelmintics were prescribed irrationally to treat diseases that were tentatively diagnosed as nonparasitic cases, and 92.1% of anthelmintics were utilized to treat diseases that were tentatively diagnosed without getting correct laboratory supported diagnosis. This may be due to inadequate recognition of the disease, unavailability of diagnostic aids for confirmatory tests, and absence of the right drug to make the treatment broader anthelmintics can be given in combination with other drugs [ 69].
There also other studies conducted in this country from October 2006 to May 2007 indicated the proportion of tetracycline residue levels in beef at Addis Ababa, Debre Zeit, and Nazareth slaughterhouses in central Ethiopia. Out of the total 384 samples analyzed for tetracycline residue, 71.3% had detectable oxytetracycline levels. Among the meat samples collected from the Addis Ababa, Debre Zeit, and Nazareth slaughterhouses, 93.8%, 37.5%, and 82.81% tested positive for oxytetracycline, respectively [ 50]. Agricultural pesticides are important chemicals that are used to mitigate crop damage or loss and improve productivity. However, pesticides may cause negative environmental and human health effects depending on their specific distribution and use. Its residue has become a major food safety hazard; synergy toxic made it a much higher risk. The toxicity of organic phosphorus, organochlorine, carbamate, and other pesticides is mainly manifested as neurotoxicity [ 42].
Control and Preventive Measures Drug Residue on Animal Products
The first step in residue prevention is to make individuals and organizations aware of the problem through education by means of scientific literature, computer databases, veterinary consultations, and the efforts of national organizations [ 71]. Government is responsible for the preparation and implementation of the regulatory laws for food safety [ 22]. According to section 31 of the FSS Act, 2016, “no person shall commence or carry on any food business except under a license.” For the protection of consumers, the Codex Alimentarius has established MRLs and ADI for various veterinary drugs in foods (including milk). According to the Codex, few drugs such as CAP, chlorpromazine, furazolidone, dimetridazole, metronidazole, nitrofural, and some others, have no safe levels of residue, hence, should not be used in food-producing animals [ 72].
Food and Drug Authority is the international body that ensures the safety of food products and has developed a risk assessment regarding animal drug residues in milk and milk products [ 73]. As the pharmacokinetics of a drug is dependent on the vehicle or excipient used in a drug formulation the withholding time is valid for that specific drug formulation. Therefore, different withholding periods may be appropriate for the same drug in different veterinary preparations [ 74]. Furthermore, most countries mandate the drug manufacturer to provide a withdrawal time as a product label [ 75]. The presence of disease processes, for example, nephritis, mastitis, and hepatitis can substantially alter the normally accepted withdrawal times. Therefore, the veterinary practitioner should have a good knowledge of the various parameters that can influence the excretion of drugs to fix withdrawal periods according to the particular cases he has on hand [ 32].
Conclusions and Recommendations
This review revealed that drug residue in animal products causes many problems for consumers due to its impact on human health. The overall impact includes antimicrobial drug resistance, toxicity, disturbance of the function of normal flora, and carcinogenetics. Hence, the review focused on reducing drug residue from animal products following the risk factors for it and must be taken into emphasis to get safe food through participating in activity aware the community.
Based on the above conclusions the following recommendations are forwarded:
- Aware the community never takes to the market place animals injected with antibiotics before finishing the withdrawal period reduced antibiotics residues, particularly in the veterinary field.
- Serious national legislation must be passed around the world to avoid illegally used antibiotics.
- Detaining the animals’ carcasses by meat inspectors when see any color on injection muscle in an abattoir.
- Restrict the use of antibiotics in the veterinary field without a veterinarian’s prescription.
- Avoidance of antibiotics that have not stated the ingredient content.
- Avoidance of antibiotics that have not been packed with leaflets.
- Antibiotic use in food animals should be reduced by improving animal health through biosecurity measures.
- Antibiotics should be administered to food animals only by professionals.
- Narrow-spectrum antibiotics should be the first choice when antibiotic therapy is justified.
- Use of antibiotics as growth promoters should be prohibited.
- Antibiotics should be used therapeutically and administered to sick animals based on clinical diagnoses.
- Veterinary extensions and practices must be promoted in Ethiopia.
List of Abbreviation
AMR, Antimicrobial drug resistance; CAP, Chloramphenicol; CL-ELISA, Competitive indirect chemiluminescent enzyme-linked immunoassay; ELISA, Enzyme linked immunosorbent assay; HBGV, Health-based guidance value; HPLC, High-performance liquid chromatography; MRL, Maximum residue limit; and TLC, Thin layer chromatography.
Acknowledgment
First and foremost, the author would like to praise his almighty ALLAH who prolonged his life and helped and will help him throughout his life.
Furthermore, special thanks to special persons who will always be in his heart, his family, especially his wife, who never gets on his life because she is his everything in this world, for her support and encouragement throughout his life, until now.
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