REVIEW ON CURRENT STATUS OF VETERINARY DRUGS RESIDUES

IN BEEF MEAT; ITS RISK FACTOR AND PUBLIC HEALTH IMPACT.

ADVANCED TOPIC IN VETERINARY PUBLIC HEALTH

AHIMED JEMALO

July, 2022

HARAMAYA, ETHIOPIA
REVIEW ON CURRENT STATUS OF VETERINARY DRUGS RESIDUES
IN BEEF MEAT; ITS RISK FACTOR AND PUBLIC HEALTH IMPACT.

A Paper Presented for Course: Seminar on Current Topics in Veterinary

Public Health (MVPH 732)

Haramaya University College of Veterinary Medicine Master Program in

Veterinary Public Health

By: Ahimed Jemalo

ID NO. PGP/883/14

Advisor: Adem Hiko (DVM, Msc, PhD)

July, 2022
Haramaya, Ethiopia
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APPROVAL SHEET

As a seminar advisor, I hereby certify that I have read and evaluated this review prepared under
my guidance by Ahimed Jemalo on title review on current status of veterinary drugs residues
in beef meat, its risk factor and public health impact. I recommend that it can be submitted as
fulfilling review requirement.

__________________________ ____________________ _____________________

Advisor Signature Date

As members of board examiners of seminar open defense examination, we certify that we have
read and evaluated review prepared by Ahimed Jemalo. We recommend that review be accepted
as fulfilling review requirement for postgraduate seminar on current veterinary public health
topics.

1. __________________________ ____________________ _____________________

Examiners Signature Date

2. __________________________ ____________________ _____________________

Examiners Signature Date

Final approval and acceptance of review is contingent upon submission of comment from board
of final copy of CVM after inclusion of comments from board of examiners.
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ACKNOWLEDGEMENTS

First and foremost I would like to thank to the almighty Allah for giving me all I need throughout
my life.
Secondly, I would like to extend my deepest gratitude toward my advisor, Prof. Adem Hiko for
his valuable guidance and advice. He inspired me greatly to work on this paper. His willingness
to motivate me contributed tremendously to my paper.
Also, I would like to extend my appreciation to Haramaya University, particularly College of
Veterinary Medicine for their inspiration and assistance to bring into picture this seminar paper.
Lastly but not the least, an honorable mention goes to my family and friends for their supporting
me.
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TABLE OF CONTENT
APPROVAL SHEET ii
ACKNOWLEDGEMENTS iii
TABLE OF CONTENT iv
LIST OF ABBRIEVATION AND ACRYNOMY v
LIST OF TABLE vi
LIST OF FIGURE vii
SUMMARY viii
1. INTRODUCTION 1
2. LITERATURE REVIEW 4
2.1. Historical Background 4
2.2. Veterinary Drugs and Their Use in Food Animals 6
2.3. Risk Factors for the Development of Veterinary Drug Residues in Beef Meat. 7
2.3.1. Age of Animal and Type of Feed 8
2.3.2. Disease Status 8
2.3.3. Extra-Label Drug Use 8
2.3.4. Improper Withdrawal Time 8
2.4. Potential Effects of Veterinary Drug Residues in Beef Meat on Public Health 8
2.4.1. Short Term and Direct Effect 9
2.4.2. Long Term and Indirect Effect 9
2.5. Safety Evaluation and Detection Methods of Veterinary Drug Residues in Beef Meat 10
2.5.1. Safety Evaluation 10
2.5.2. Detection Methods 11
2.6. The Extent of Veterinary Drugs Residues in Africa 11
2.7. The Extent of Veterinary Drugs Residues in Ethiopia 14
2.8. Control and Preventive Measures of Veterinary Drugs Residues 15
2.9. Conclusion and Recommendations 16
3. REFERENC 17
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LIST OF ABBRIEVATION AND ACRYNOMY

ADF Animal derived food

ADI Acceptable daily intake

AGP Antimicrobial growth promoter

AGPs Antimicrobial growth promoters

AMR Antimicrobial resistance

APCI Atmospheric pressure chemical ionization

CAC Codex Alemintrius Commission

CVM Center for veterinary medicine

DNA Deoxyribonucleic acid

EC European Commission

ELDU Extra-label drug use

ELISA Enzyme linkedimmunosorbant

ESI Electrospray ionization

FDA Food and drug administration

HPLC High performance liquid chromatography

JECFA Joint expert committee food additive

MRL Maximum residue limit

NOEL No observed effect level

NSAID Non-steroid anti-inflammatory drug

RNA Ribonucleic acid

SPR Surface Plasmon Resonance

VMP Veterinary medicinal product

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LIST OF TABLE

Table 1. International food standards of Codex alimentarius commission (CAC) for (ADI) and
(MRL) of Veterinary drugs residues in beef cattle..........................................................................5
Table 2. Antibiotic contamination in various foodstuffs consumed in African countries.............12
Table 3 .Veterinary drugs residue concentration that exceeds above ADI or MRL (µg/kg).........13
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LIST OF FIGURE

Figure 1. Classifcation of antibiotics used in food-producing animals (adapted) ..........................7

Figure 2. Human health concerns of veterinary drugs residues in food tuffs from animal source..9
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SUMMARY

The global population is experiencing rapid growth, which poses significant challenges to food
security worldwide. Alongside this trend, there is a notable surge in the demand for animal-
derived products, driven partly by increasing household incomes. This increase in demand for
high-quality animal protein underscores the importance of safeguarding animal health against
infectious diseases and enhancing their performance. Meeting this demand requires an increase
in the use of veterinary therapeutics. To sustain the production of high-quality beef and other
animal products, veterinarians and farmers often employ veterinary drugs in agricultural
practices, both as treatments and growth promoters. However, the indiscriminate use of these
drugs carries potential risks to human health. Residues of these veterinary medicines, including
pharmacologically active substances, their breakdown products, and metabolites, can persist in
animal tissues intended for human consumption. These residues tend to concentrate in storage
tissues such as body fat or in organs involved in metabolism and excretion, such as the liver and
kidneys. Several factors contribute to the development of drug residues, including off-label use,
improper withdrawal periods and the health status of the animals, their feeding regimen, and age.
Addressing these issues is essential to ensure the safety of animal-derived food and to mitigate
potential health risks associated with veterinary drug residues.

Keywords: Beef, Drugs, Human health, Residue, Veterinary drug

1. INTRODUCTION
The global population is on a rapid upward trajectory, projected to exceed 9.8 billion people by
2050 according to the Population Division of the United Nations Department of Economic and
Social Affairs (UNESA, 2017). This surge in population, particularly evident in many sub-
Saharan African nations such as Ethiopia, is accompanied by rapid urbanization and increased
food demand (Kc et al., 2018). As household incomes improve, the demand for animal-derived
foods (ADFs) is also expected to increase, adding to the existing challenges of food security
worldwide (Enahoro et al., 2019). The projections indicate a staggering 70% increase in global
meat consumption by 2050, necessitating innovative approaches to meet the increasing demand
for high-quality protein (Hocquette et al., 2018). To address this demand, veterinarians and
farmers are increasingly resorting to the use of veterinary drugs in animal husbandry, employing
them as antimicrobial growth promoters (AGP) and for disease control strategies (Lei et al.,
2015; Marshall and Levy, 2011).

In Ethiopia, the industry stands out as a rapid solution to protein deficiency, offering rapid
turnover rates, employment opportunities for young people, cultural significance as a revered
meat and a means of combating malnutrition. Consequently, there is a pressing need to upscale
beef production, leading to widespread use of veterinary drugs, particularly antimicrobials
(Behnke, 2010). However, these antimicrobials and their metabolites tend to accumulate in
animal tissues, forming residues at varying concentrations (Beyene, 2016; Modi et al., 2013).

A "veterinary drug" is defined as any substance or combination of substances intended for use in
animals, either for diagnosing, treating, mitigating, or preventing disease, abnormal physical or
mental states, or their symptoms (Fingleton, 2004). Additionally, they may be used to restore,
correct, or modify any physical, mental, or organic function in animals. The use of veterinary
drugs in livestock production is indispensable, serving various purposes, such as therapeutic
treatment of diseases, prophylactic prevention of illnesses, modification of physiological
functions (eg tranquilizers, anesthetics), enhancement of growth and productivity (eg growth
promoters) and ensuring food safety (Aidara-Kane et al., 2018). These drugs are used worldwide
and encompass a wide range of chemical compounds, including vaccines, antimicrobials,
antiparasitics, and β-agonists (Espinoza et al., 2020). Their use has contributed significantly to
the improvement of profitability and productivity in modern food-animal production systems by
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allowing earlier weaning, accommodating higher animal densities, increasing carcass yield and
meat quality, and enabling the utilization of more cost-effective feed sources (Falowo and
Akimoladun, 2019).

Among the various categories of veterinary drugs, antimicrobials are of particular significance
and are the most commonly used. They encompass medicines of natural, synthetic, or semi-
synthetic origin that inhibit the growth of or destroy microorganisms in low concentrations
without causing harm to the host (Prajwal et al., 2017). Commonly used antimicrobials in
livestock production include tetracyclines, β-lactams, sulphonamides, aminoglycosides,
macrolides, fluoroquinolones, and amphenicols (Alhaji et al., 2018). In addition, antiparasitic
agents, such as anthelmintics or coccidiostats, include substances such as thiabendazole,
closantel, imidocarb, diminazene, and sedatives (Prajwal et al., 2017). When it comes to drug
residues in animals intended for food production, antibacterial and antiparasitic compounds stand
out because of their widespread use in animal husbandry. Antiparasitic drugs, in particular, have
significant economic importance and directly impact animal health, ranking second (23% market
share) after biological products in the global animal health market, with antibiotics closely
following in third place with 16% of sales (Selzer and Epe, 2021).

The administration of antibiotics to food-producing animals requires careful consideration, as

excessive use can lead to the accumulation of drugs in animal tissues such as muscles, heart,
liver, and kidneys, often exceeding the maximum residue levels (MRLs) considered safe (Araby
et al., 2020). Factors contributing to drug residue accumulation include inadequate monitoring of
withdrawal periods, improper treatment regimens, overdose, or the use of banned antibiotics for
economic reasons (Agmas and Adugna, 2018). Consumption of tissues containing drug residues
poses various risks to human health, including toxic effects, transfer of antibiotic resistant
bacteria, immunopathological effects, carcinogenicity, bone marrow toxicity, neurotoxicity,
teratogenicity, and allergic reactions (Babapour et al., 2012; Sanz et al., 2015). Prolonged
exposure to subtherapeutic antibiotic doses also contributes to the development of antibiotic-
resistant bacterial strains, which can transfer antimicrobial resistance (AMR) genes to other
bacterial organisms, posing challenges in predicting their impact on human health (Sahu et al.,
2014). Maintaining a clean and healthy environment for food animals, along with the rational use
of veterinary drugs, is crucial for protecting human health. Although veterinary drugs play a vital
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role in disease control and prevention in animals and in promoting the growth of food animals,
their misuse can lead to issues such as the development of antimicrobial resistance in
microorganisms and residue effects in both animals and humans.

Therefore, the objectives of this paper are:

 To review existing literature and explore risk factors associated with veterinary drug
residues in beef animal products.
 To address the public health implications of veterinary drug residues in beef cattle
products.
 To outline the suggested control and preventive measures for the management of
veterinary drug residues on beef cattle farms.
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2. LITERATURE REVIEW

2.1. Historical Background

A multitude of known and emerging foodborne biological and chemical hazards pose significant
threats to public health (FAO, 2008). In response to a series of health crises, the European Union
(EU) has shifted its food safety mechanism toward a risk analysis approach, emphasizing 'farm-
to-fork' risk management (Lefeuvre, 2003). This transition has led to the establishment of food
safety agencies at the European level, with a focus on addressing risks associated with residues
from veterinary medicinal products (VMPs) used in livestock production, notably through
harmonization of regulations on veterinary medicinal products in the 1980s. In recent years, the
EU has strengthened its regulatory framework to better supervise, assess, monitor, and control
food production through the ‘Food Law’. In particular, the use of anti-infectives in livestock and
its role in the development of antimicrobial resistance have garnered significant attention,
prompting the introduction of community and national surveillance programs for zoonotic
bacteria (Authority and Control, 2012).

Residues, as defined by the European Union (EU) and the Center for Veterinary Medicine
(FDA/CVM) in the USA, encompass pharmacologically active substances, including active
principles, excipients or degradation products, and their metabolites remaining in food obtained
from animals treated with the respective VMPs (Beyene, 2016). Under normal physiological
conditions, after drug administration to an animal, most drugs undergo metabolism for
elimination and detoxification. Typically, the parent product and its metabolites are excreted
primarily via urine and to a lesser extent through feces (Boothe and Reevers, 2012). However,
these substances can also be present in meat, milk and eggs (Vich, 2011).

Ideally, no product from a treated animal should be consumed until all drugs administered have
been eliminated, a principle known as zero tolerance. However, advancements in analytical
techniques have led to the detection of residues at extremely low concentrations, measured in
parts per million (ppm), parts per billion (ppb), and even parts per trillion (ppt). While residues
may often be detectable using high-efficiency analytical methods such as high-performance
liquid chromatography (HPLC), they are typically present at concentrations not inherently toxic
(Rico and Burgat-Sacaze, 1985). According to the general standards of the Codex Alimentarius
 5

Commission (CAC), the following table illustrates acceptable daily intake (ADI) and maximum
residue limits (MRL) of veterinary drug residues in beef meat.

International food standards of Codex alimentarius commission (CAC) for (ADI) and
Table 1.
(MRL) of Veterinary drugs residues in beef cattle.

Class of Veterinary Drug Species of ADI Target Tissue of MRL (µg/kg)

Veterinary Drug or Antibiotic Animal (µg/kg bw)
Muscle Liver Kidney Fat
Antihelmentic Albendazole n.s 0-50 100 5000 5000 100

Fenbendazole Cattle 0-7 100 500 100 100

Thiabendazole Cattle 0-100 100 100 100 100
Triclabendazole Cattle 0-3 250 850 400 100

Closantel Cattle 0-30 1000 1000 3000 3000

Ivermectin Cattle 0-10 30 800 100 400
Antiprotozoal Diminazene Cattle 0-100 500 12000 6000 -

Imidocarb Cattle 0-10 300 1500 2000 50

Isometamidium Cattle 0-100 100 500 1000 100

β-lactams Amoxicillin Cattle 0-2 50 50 50 50

Ampicillin Fish 0-3 50 50 50 50

Benzyl/procaine Cattle 0-3 50 50 50 -

penicillin
Cephalosporin Ceftiofur Cattle 0-50 1000 2000 6000 2000

Tetracycline Oxytetracycline Cattle 0-30 200 600 1200 -

Chrotetracycline Cattle 0-30 200 600 1200 -

Tetracycline Cattle 0-30 200 600 1200 -

Macrolides Erythromycin Chicken 0-0.7 100 100 100 100

Spiramycin Cattle 0-50 200 600 300 300

Tylosin Cattle 0-30 100 100 100 100

Tilmicosin Cattle 0-40 100 1000 300 100

Aminoglycoside Streptomycin Cattle 0-50 600 600 1000 600

Neomycin Cattle 0-60 500 500 10000 500

Gentamycin Cattle 0-20 100 2000 5000 100

Spectinomycin Cattle 0-40 500 2000 5000 2000

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Sulfonamide Sulfadimidine n.s 0-50 100 100 100 100

Sulfathiazole - - - - - -

Fluoroquinolone Ciprofloxacin - - - - - -

Levofloxacin - - - - - -

Amphenicols Chloramphenicol - - - - - -

Thiamphenicol - - - - - -

NB!: n.s=not specified

2.2. Veterinary Drugs and Their Use in Food Animals

Drug use in food animals is integral to its health, welfare, and economic viability. These drugs
serve various purposes, including the therapeutic treatment of infections, prophylactic prevention
of diseases, and promotion of growth. Therapeutic use involves treating established infections,
while prophylaxis involves administering drugs to individuals or groups to prevent infections
from developing. Growth promoters are antimicrobial agents administered in low or
subtherapeutic doses to inhibit microbial growth, resulting in improved quality meat with
reduced fat content and increased protein levels (Beyene and Tesega, 2014).

Antibiotics, derived from natural, synthetic, or semisynthetic sources, are the most commonly
used veterinary drugs. They inhibit microbial growth or destroy microorganisms and are widely
used in beef industries around the world due to their availability and affordability. In veterinary
medicine, antibiotics are used for therapeutic, prophylactic, nutritional, and growth-promoting
purposes, as well as to alleviate pain and suffering in animals (Kohanski et al., 2010; Wassenaar,
2005)

Currently, approximately 80% of food animals receive antibiotics during part or most of their
life, potentially leading to residue accumulation in animal products such as meat, milk, and eggs
(Bayou and Haile, 2017). Antibiotics used in food-producing animals can be classified into six
major groups, with sulfonamides being the most commonly used, followed by fluoroquinolones,
aminoglycosides, phenicols, β-lactams, tetracyclines, and oxazolidinones. These antibiotics are
generally administered to livestock via feed, drinking water, or injection to treat diseases and
promote growth (Clark et al., 2012; Mole, 2013).
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Figure 1. Classifcation of antibiotics used in food-producing animals (adapted) (Mungroo and

Neethirajan, 2014).
Parasitic helminth infections pose significant challenges to food-producing animals worldwide,
leading to economic losses. Consequently, antihelminthic drugs are frequently used in livestock,
resulting in the presence of residues in edible animal products. Residue exposure tends to be
higher in regions with widespread use of antihelminthic drugs and greater consumption of locally
sourced cattle products. For instance, ivermectin, a widely used drug, has a lipophilic nature,
leading to extended withdrawal periods and presence in edible parts of treated animals,
particularly those with high fat content (Baynes et al., 2000).

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in veterinary practice to

treat inflammation, pain, respiratory diseases, fever, and musculoskeletal disorders. They also
contribute to improving animal production and improving meat quality. Following
administration, NSAIDs bind to plasma proteins, undergo absorption and distribution in tissues
and fluids, and are eventually excreted as glucuronic conjugates (Gallo et al., 2010; Mainero
Rocca et al., 2017 ).

2.3. Risk Factors for the Development of Veterinary Drug Residues in Beef Meat.

The presence of veterinary antibiotic residues in food of animal origin remains a significant
global concern due to the extensive use of these compounds for various purposes, including
preventive and curative therapeutic treatments, as well as additives or growth promoters in food
production (Berghiche et al., 2019). Such residues pose a major challenge to food safety and can
result from several factors, including non-compliance with recommended label directions or
dosages (extra label usage), failure to adhere to recommended withdrawal times, administration
 8

errors, equipment contamination, and improper cleaning practices (Okocha et al., 2018). Several
factors contribute to the development of residues in food of animal origin.

2.3.1. Age of Animal and Type of Feed

The age and weaning status of animals can influence drug disposition, with weaned or adult
animals generally exhibiting higher clearance times compared to unweaned or young animals.
Diets can also affect drug bioavailability, with variations observed based on the type of feed
administered (Bushra et al., 2011; Mc Conville et al., 1995; Miller, 1997; Schwark, 1992;
Waterman, 2018)

2.3.2. Disease Status

Diseases can alter drug metabolism and elimination, potentially leading to increased residue
persistence. Changes in liver or renal function, often associated with infections or inflammation,
can affect drug processing and excretion, contributing to residue accumulation (Bayou and Haile,
2017; Falowo and Akimoladun, 2019).

2.3.3. Extra-Label Drug Use

ELDU refers to the use of approved drugs in a manner not in accordance with the instructions on
the label, including the use in unapproved species or conditions, or in doses exceeding the
recommended doses. Common examples include using drugs approved for injection as topical
medications, which can lead to unintended residue issues (Gillian, 2003).

2.3.4. Improper Withdrawal Time

The withdrawal time, the period required for residues to reach safe concentrations after drug
administration, varies for different antibiotics. Failure to adhere to the specified withdrawal times
can result in the presence of antibiotic residues in edible animal tissues, posing risks to
consumers (Mitchell et al., 2020; Rana et al., 2019).

2.4. Potential Effects of Veterinary Drug Residues in Beef Meat on Public Health

In general, public health agencies are deeply concerned about the presence of drug residues in
the meat and edible tissues of food-producing animals. While low-level contamination may not
immediately pose a public health violation, the persistence of drug residues in edible tissues can
lead to their introduction into the human diet, often due to farmers neglecting withdrawal periods
or improper administration of drugs (Kabir et al., 2004; Tajick and Shohreh, 2006). The use of
 9

drugs in food animals poses risks to public health, as these residues can be secreted in animal
tissues intended for human consumption (Salehzadeh et al., 2007; Tilahun et al., 2016). There are
several pathways through which drug residues can adversely affect human health, including:

Figure 2. Human health concerns of veterinary drugs residues in food tuffs from animal source.

2.4.1. Short Term and Direct Effect

Allergic reactions: Drug hypersensitivity reactions, including allergic responses mediated by IgE
antibodies, can occur after drug administration. Antibiotics, particularly penicillin, are commonly
associated with allergic reactions, although the extent of hypersensitivity in animals remains
unclear (Boothe and Reevers, 2012; Riedl and Casillas, 2003).

Development of Drug Resistance: Antimicrobial usage in veterinary medicine can lead to the
presence of antimicrobial residues in animal-derived food products. Irrational use of
antimicrobials can contribute to the selection and spread of antimicrobial resistant strains, posing
significant public health threats and increasing the severity and frequency of infections (Watkins
and Kožárová, 2019; WHO, 2017).

2.4.2. Long Term and Indirect Effect

Carcinogenic effects: Antibiotic residues in food of animal origin have been linked to
carcinogenic potential due to their ability to bind to intracellular components such as proteins,
DNA, RNA, and phospholipids (Darko et al., 2017; Jabbar, 2013).
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Mutagenic Effects: Certain drugs and environmental chemicals have mutagenic activity,
potentially leading to DNA mutations or damage, which can adversely affect human fertility
(Booth, 1988; Firth and Hurst, 2017).

Teratogenic effects: Some drugs, such as benzimidazole anthelmintics, exhibit embryotoxic and
teratogenic properties when administered during early pregnancy, resulting in congenital
malformations (Akansale, 2019; El-Makawy et al., 2006).

Disruption of the Normal Intestinal Flora: Antibiotics present in food residues can alter the
normal intestinal flora essential for human health, affecting nutrient absorption, immune system
function, and protection against pathogen invasion (Bäckhed et al., 2004; Myllyniemi et al.,
2000; Round and Mazmanian, 2009).

2.5. Safety Evaluation and Detection Methods of Veterinary Drug Residues in Beef Meat

2.5.1. Safety Evaluation

Acceptable Daily Intake (ADI): ADI is a measure of the amount of a substance that can be
safely ingested daily for a lifetime without causing appreciable health risks. Calculating the ADI
involves a comprehensive toxicological safety evaluation that considers both acute and long-term
exposure to the drug and its potential effects. Typically, if the drug is not carcinogenic, the ADI
is determined by dividing the level of no observed effect (NOEL) of the most sensitive effect in
the most sensitive species by a safety factor. The Food and Drug Administration (FDA)
calculates the safe concentration for each edible tissue using ADI, the weight of an average adult
(60 kg), and the amount of the product consumed per day in grams, i.e; Safe concentration =
[ADI (µg/kg/day) x 60 kg] / [grams consumed / day].

Maximum Residue Limit (MRL): The MRL is the maximum concentration of a residue resulting
from veterinary drugs that is legally permitted or recognized as acceptable in or on a food,
agricultural commodity or animal feed. It is expressed in milligrams per kilogram of the
commodity or in milligrams per liter for a liquid commodity.

Calculating withdrawal period: The withdrawal period is determined when the residue
concentration in edible or target tissues falls below the permissible concentration. Withdrawal
times are typically determined in primary elimination organs, such as the liver or kidneys, as
these tissues often show residues for the longest duration.
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2.5.2. Detection Methods

Screening Methods: The detection of antibiotic residues in animal-derived food products began
early in the history of antibacterial therapy in veterinary medicine. Screening methods offer
advantages such as automation, rapid results, and good sensitivity and specificity, and detection
capabilities with low error probability.

Biological Methods: Biological screening methods were among the first to be developed and are
still widely used due to their cost-effectiveness and broad spectrum. Although not selective, they
can cover various chemical classes of antibiotics and detect cellular responses to antibiotic
residues.

Immunological Methods: Immunological methods are based on specific antigen-antibody

interactions for particular residues. Techniques such as the enzyme-linked immunosorbent assay
(ELISA) provide rapid results with good specificity and sensitivity, making them suitable for
analyzing a large number of samples.

Biosensors: Biosensors integrate biological elements with physiochemical transducers to produce

electronic signals proportional to the analytes. They offer rapid detection and measurement of
specific residues and are considered a modern approach to detection methods. Surface Plasmon
Resonance (SPR) is an example of a biosensor.

Chromatography Methods: Chromatography methods are used for the unambiguous

identification and confirmation of veterinary drug residues in food products of animal origin.
Although these methods are time-consuming and require specialized equipment and trained
personnel, they offer precise identification and quantification of residues. Examples include
liquid chromatography-mass spectrometry with atmospheric pressure chemical ionization (APCI)
and high-performance liquid chromatography-electrospray ionization (ESI) tandem mass
spectrometry.

2.6. The Extent of Veterinary Drugs Residues in Africa

On a global scale, over half of all medications are prescribed, dispensed, or sold improperly,
leading not only to waste and increased expenses, but also to significant risks to individual
patient health and public health overall, exacerbating the issue of chemical agent misuse. In
Africa, in addition to the reckless use of antibiotics in human medicine, the agricultural sector
 12

consumes a considerable share (50%) of antibiotics in animal agriculture to treat diseases or

prevent outbreaks and promote animal health. However, many African countries lack clear
regulations governing antibiotic contamination of feedstuffs, and there is a notable scarcity of
information regarding antibiotic residues in animal-derived foods across the continent. In
numerous African nations, including Ethiopia, veterinary antibiotics are often used
indiscriminately to treat bacterial diseases or added as feed additives for domestic animals and
birds. The widespread threat of antibiotic contamination presents a significant challenge to
public health, not only for African populations but also on a global scale, with residues spreading
rapidly regardless of geographical, economic, or legal disparities between countries.

The Joint FAO/WHO Expert Committee on Food Additives (JECFA) has documented various
veterinary drug residues in working documents and is actively involved in the evaluation of the
safety of these residues in food. JECFA establishes acceptable daily intakes (ADIs) and
recommends maximum residue limits (MRLs) for substances when administered to food-
producing animals in accordance with good veterinary practice. The following table highlights
the incidence of residues of veterinary antibiotic drugs in food of animal origin in selected
African countries.

Table 2. Antibiotic contamination in various foodstuffs consumed in African countries.

Country Veterinary Drugs Residues Animal and Animal Derived Reference

Food Stuff
Classes Antibiotics Species of Edible Tissue
Animal or Organ
South Tetracycline, Oxytetracycline, Cattle, Cattle Carcass, (Ramatla et al., 2017)
Africa Sulfonamides, Sulfamethazine, Chicken, Liver, Kidney, (Adesiyun et al., 2021)
Quinolones, Ciprofloxacin, Pork Milk, Chicken (Bester SH, 1979)
Aminoglycoside Streptomycin Meat and Egg,
Pork Carcass
and Organ
Ethiopia Tetracycline, β- Oxytetracycline, Cattle, Cattle Carcass, (Agmas and Adugna,
lactams, Penistripe, Chicken, Liver, Kidney, 2018); (Bedada et al.,
Macrolides, Gentamycin, Pork Chicken Meat 2012) ; (Myllyniemi et
Sulfonamides, Sulfamethazine, and Egg, Pork al., 2000)
Aminoglycoside, Chloramphenicol Carcass and
Amphenicols Organ
 13

Kenya β-lactams, Penicillin-G, Cattle Beef Carcass, (Muriuki et al., 2001);

Tetracycline, Oxytetracycline Liver, Kidney (Shitandi and Sternesjö,
and Milk 2001)
Sudan Quinolones, Oxytetracycline, Cattle All Animal (Goudah et al., 2007),
Tetracycline, Ciprofloxacin, Derived Food (Eltayb et al., 2012)
Macrolides Tylosin Stuff
Egypt Tetracycline, β- Oxytetracycline, Cattle, Chicken Meat (Salama et al., 2011),
lactams, Cephalosporin Chicken, and Egg, (Hussein et al., 2013),
Rabbit Bovine Carcas, (Khattab et al., 2010),
Rabbit Meat, (AM et al., 2001)
Liver, Kidney
Zambia Tetracycline, Oxytetracycline, Cattle Beef Meat and (Nchima et al., 2017)
Sulfonamides Sulfamethazine Organ
Tanzania Amphenicols, Oxytetracycline, Cattle, Meat and (Kurwijila et al., 2006)
Tetracycline Chloramphenicol Chicken Milk, Chicken (Nonga et al., 2010)
Meat and Egg
Nigeria Tetracycline, β- Proc/Penicillin, Cattlle, Almost all (Ezenduka et al., 2011),
lactams, Oxytetracycline, Chicken Cattle and (Omeiza et al., 2012),
Amphenicols Chloramphenicol Chicken (Olatoye and Ehinmowo,
Derived Food 2010),
Stuff (Ibrahim et al., 2010)

Livestock production represents one of the fastest-growing agricultural sectors globally, yet the
health and growth of livestock are often hindered by diseases caused by various infectious
microorganisms. Current estimates suggest that the global average annual consumption of
antimicrobials per kilogram of animal produced exceeds 100 mg/kg. Alarmingly, approximately
80% of antibiotics administered in veterinary settings are used as growth promoters, surpassing
the total of antibiotics used for human medical care. The following table illustrates veterinary
drug residue concentrations that exceed ADI or MRL (µg/kg) in various types of animal tissue or
organs in different African countries.

Table 3 .Veterinary drugs residue concentration that exceeds above ADI or MRL (µg/kg).
Country Veterinary Species of Target CAC of ADI CAC of Concentr/ Reference
Name Drugs Animal Tissue or (µg/kg bw) MRL Above
Organ (µg/kg) ADI/MRL
(µg/kg)
Ethiopia Tetracycline Beef Cattle Liver 0-30 600 570 (Bedada et
Kidney 0-30 1200 440 al., 2012)
Muscle 0-30 200 320
Penistrip Beef Cattle - 0-30 50 5 (Agmas
Sulfonamide Beef Cattle - 0-50 100 100 and
 14

Adugna,
2018)
South Tetracycline Different In different 0-30 600 170 (Ramatla et
Africa Types of parts of al., 2017)
Animal animal (Adesiyun
Tissue et al.,
Streptomycin Beef Cattle Kidney 0-50 600 650 2021)
Chicken Muscle 0-50 600
Sulfonamide Different In different 0-50 100 60
Types of parts of
Animal animal
Ciprofloxacin Pork Liver n.m n.m 150
Muscle n.m n.m
Nigeria Tetracycline Beef Cattle Liver 0-30 600 1946 (Olatoye
Kidney 0-30 1200 678 and
Muscle 0-30 200 220 Ehinmowo,
2010)
Penicillin Beef Cattle - 0-30 50 80 (Ibrahim et
al., 2010)
Kenya Tetracycline Beef Cattle Liver 0-30 600 1380 (Muriuki et
Kidney 0-30 1200 1090 al., 2001)
Muscle 0-30 200 790
NB!: n.m=not mentioned

2.7. The Extent of Veterinary Drugs Residues in Ethiopia

A study conducted at the University of Gondar veterinary clinic from March 2016 to June 2016
in Ethiopia revealed that anthelmintic drugs were commonly but improperly used. Three groups
of anthelmintics, benzimidazoles (albendazole, fenbendazole, mebendazole and triclabendazole),
imidazothiazoles (tetramisole and levamisole) and macrocyclic lactones (ivermectin), were
frequently used. However, prolonged use of a limited group of drugs may increase the risk of
developing resistance, which in turn is a risk factor for drug residues (Kassahun et al., 2016).

Another study conducted in Ethiopia in 2007 focused on tetracycline levels in beef sampled from
slaughterhouses in Addis Ababa, Bishoftu and Adama. Of the 384 samples analyzed for
tetracycline residue, 71.3% had detectable oxytetracycline levels. Among the meat samples
collected from these slaughterhouses, 93.8%, 37.5%, and 82.1% tested positive for
oxytetracycline, respectively (Mengistie et al., 2016).

Furthermore, a study conducted from June 2017 to November 2017 in Debre Tabor and Bahir
Dar, located in the northwest of the country, indicated elevated levels of antimicrobial residues in
beef cattle samples. Of the 250 beef cattle slaughtered and sampled, 76.4% were from the liver
 15

and kidney in both, 43.6% from the thigh muscle, and 42% from fat. These findings showed a
higher prevalence of antimicrobial residues compared to other African countries such as Nigeria
(54.44%), Kenya (45.6%), Ghana (30.8%) and Sudan (17.33%) (Aning et al., 2007; Ezenduka et
al., 2011; Mohamed et al., 2011; Muriuki et al., 2001).

2.8. Control and Preventive Measures of Veterinary Drugs Residues

The misuse of veterinary drugs, particularly when administered to food-producing animals,

presents a significant challenge. This practice raises concerns about the possible presence of drug
residues, including minimal amounts of drugs and their metabolites, in edible tissues and animal
products such as meat, milk, eggs and fish, which can pose health risks to humans consuming
these foods (Sanders, 2007).

In the European Union (EU), efforts to monitor and control residues rely on standardized
analytical methods. The regulatory framework, governed by Directive 96/23/EC, establishes a
network of approved laboratories for official residue control, setting criteria for the quality and
efficacy of analytical methods (Decision 2002/657) (Mensah et al., 2014). The residue control
strategy follows a two-step approach: first, detecting residues using sensitive tests with minimal
false negatives, and second, confirming and quantifying against Maximum Residue Limits
(MRLs) with minimal false positives.

Therefore, the strategy to prevent residues from entering food of animal origin intended for
human consumption is based on the proper drug use guidelines developed for both veterinarians
and food animal producers. This involves using drugs only when necessary, in the correct
manner, at the appropriate time and at the right dosage, while adhering to withdrawal periods.
Other preventive measures include herd health management, the use of approved drugs, the
establishment of valid veterinarian-client-patient relationships, proper drug administration and
animal identification, meticulous maintenance of treatment records, and ensuring access to
adequate drug residue testing capabilities on and off the farm (Beyene, 2016; Gerald and Joseph,
1991; Scippo et al., 1994).
 16

2.9. Conclusion and Recommendations

Globally, a significant portion of drugs are prescribed, dispensed or sold improperly. Many
livestock producers administer medications to their animals independently. The rational use of
veterinary drugs has been instrumental in controlling and preventing diseases in animals and
promoting the growth of food animals. However, irrational drug use practices, such as misuse,
excessive use, and failure to adhere to withdrawal periods, contribute to issues such as the
development of resistant microorganisms in animals and the presence of drug residues in food of
animal origin, which pose significant risks to public health. On the basis of the above findings,
the following recommendations are proposed:

 Government Regulation: Authorities must regulate the irrational and

unauthorized use of drugs and implement residue control strategies such as
management practices and herd health programs to maintain animal health and
productivity, thus minimizing the occurrence of drug residues.
 Research Support: Researchers should be encouraged to develop new, safe
methods to eliminate or reduce drug residues from animal bodies. Efforts to
identify alternative protein sources comparable to those of animal protein
should also be supported.
 Record-keeping and identification: Proper maintenance of treatment records
and identification of treated animals are crucial. Withdrawal times should be
strictly observed and enforced.
 Awareness campaigns: Initiatives to raise awareness among farmers,
consumers, and health professionals about drug residues and their implications
for public health should be prioritized.
 17

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