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Veterinary Drug Residue: The Risk, Public
Health Significance and its Management
Mohammed Ture*, Tsegaw Fentie and Bushura Regassa
Department of veterinary medicine and animal science, University of Gonder, Ethiopia
Submission: July 3, 2019; Published: July 26, 2019
*Corresponding author: Mohammed Ture, Department of veterinary medicine and animal science, University of Gonder, Ethiopia
How to cite this article: Mohammed Ture, Tsegaw Fentie, Bushura Regassa. Veterinary Drug Residue: The Risk, Public Health Significance and its
Management College of Veterinary Medicine and Animal Science. Dairy and Vet Sci J. 2019; 13(2): 555856. DOI: 10.19080/JDVS.2019.13.555856
Veterinary drugs are any substances applied to or administered to animals for their therapeutic, prophylactic and diagnostic purposes or modification of physiological function or behavior. They are used throughout the world and more than half of all medicines are prescribed, dispensed or sold improperly. In Ethiopia, also different studies revealed the improper utilization of drugs is common. The use of veterinary drugs in food-producing animals has the potential to generate residues in animal derived products and poses a health hazard to the consumer. The most likely reason for drug residues might be due to improper drug usage and failure to keep the withdrawal period. The residual amount ingested is in small amounts and not necessarily toxic. The major public health significances of drug residue are development of antimicrobial drug resistance, hypersensitivity reaction, carcinogenicity, mutagenicity, teratogenicity, and disruption of intestinal normal flora. The aim of this paper is to review about risk of occurrence of veterinary drug residue, public health effects and management. Even though, veterinary drugs have a great importance in treating, preventing and diagnosing diseases, it has major public health hazards. To avoid this it is important to use these drugs rationally, the safety levels of food must be strictly observed, drug products should be used in accordance with the labeled directions and public awareness should be created on the public health significance of drug residue.
Keywords: Antimicrobial; Drug; Residue; Risk; Veterinary drug
Abbrevations: ABZ: Albendazole; ADI: Acceptable Daily Intake; AMR: Antimicrobial Resistance; APCI: Atmospheric Pressure Chemical Ionization; APEC: Asian-Pacific Economic Cooperation; BZDs: Benzimidazoles; CFR: Code of Federal Regulation; DES: Diethylstilbestrol; DNA: Deoxyribonucleic acid; EC: European Community; EFSA: European Food Safety Authority; ELDU: Extra-label drug use; ELISA: Enzyme linked-immunosorbent assay; ELU: Extra-label use; ESI: Electrospray Ionization; EU: European Union; FAO: Food and Agricultural Organization; FDA: FOOD and Drug Administration; FDACVM: Food and Drug administration Center for Veterinary Medicine; FEB: Febantel; HPLC: High-performance liquid chromatography; IgE: Immunoglobulin E; LC-MS/ MS: Liquid chromatography-mass spectrometry/mass spectrometry; MBZ: Mebendazole; MRL: Maximum Residue Level; NAP: National Academies Press; NOEL: No observed effect level; RNA: Ribonucleic acid; UEMOA: West African Economic and Monetary Union; WHO: World health organization
Veterinary drug” means any substance or mixture of substances which is used, or is manufactured, sold or represented as suitable for use, in (1) the diagnosis, treatment, mitigation or prevention of disease or abnormal physical or mental state or the symptoms thereof in an animal; or (2) restoring, correcting or modifying any physical, mental or organic function in an animal . The use of veterinary drugs in livestock production is inevitable as they are essential for treatment of diseases (therapeutic), prevention of diseases (prophylaxis), modification of physiological functions (such as tranquilizers, anesthetic drugs), improvement of growth and productivity (growth promoters)
as well as for ensuring food safety . The veterinary drugs are
used throughout the world and they comprise a broad variety of classes of chemical compounds including vaccines, antimicrobials,
antiparasitics and β-agonists . Antimicrobials are the most important and most frequently used group of veterinary drugs . Antimicrobials are medicine (natural, synthetic or semi-synthetic origin) that inhibits the growth of or destroys microorganisms when applied at low concentrations without causing host damage . Among the antimicrobials that are commonly used in livestock production are tetracyclines, amprolium, penicillin, streptomycin, sulphonamides, tylosin, aminoglycosides, β-lactams, macrolides and lincosamides, quinolones and sulfonamides . While that of antiparasitic agents include anthelmintics or coccidiostats, stilbenes, amphenicols, nitrofurans, nitroimidazoles, carbamates, pyrethroids and sedatives .
A residue, defined in the simplest terms, results when a drug or pesticide is deliberately applied to a food-producing animal or plant. Residues of veterinary drugs include the parent compounds
and/or their metabolites in any edible portion of the animal
product and include residues of associated impurities of the
veterinary drug concerned . Residual amounts of antimicrobials
or their toxic metabolites found in meat, organs or other products
such as milk and egg of food producing animals is called veterinary
drug residues . Consumption of such food products poses a
major health risk due to the failure of treatment following the
development of resistant microorganisms . Many livestock
producers treat their animals by themselves. Even if they use the
same drugs as veterinarians, they have little understanding of the
conditions and quantities to administer or the waiting periods.
The uncontrolled use of anti-infectious agents can lead to residues
in animal products, especially when users fail to respect waiting
periods. The risks of residues in foodstuffs of animal origin
could be reflected into several forms . The immediate effect
of antimicrobial residue is allergenicity and toxicity in human
through the food chain . The long-term health adverse effects
such as increased likelihood include disruption of normal human
flora in the intestine (microbiological effects), carcinogenicity,
and teratogenicity . Other drug residue problems are the
development of antibiotic-resistant microbes and drug misuse
. The objective of this paper is to review: The risk of occurrence
of veterinary drug residue, public health effects and management
A whole series of known or new foodborne biological and
chemical hazards are threatening health . In the European
Union (EU), following a string of health crises, the food safety
mechanism has evolved towards a risk analysis approach. This
shift to the concept of ‘farm to fork’ risk management  led to
the establishment of food safety agencies at the European level.
The risks of residues from veterinary medicinal products used
in livestock production were taken on board in the 1980s, most
notably through European harmonization of the regulations on
medicinal products for veterinary use. Over the past decade, the
EU has improved its regulatory framework to better supervise,
assess, monitor and control food production under the ‘Food
Law’. More recently, the use of anti-infective in livestock and its
contribution to the development of antimicrobial resistance has
attracted considerable attention .
In Africa - particularly West Africa - only microbial pathogens,
pesticide residues and aflatoxins have been the subject of
measures to protect the safety of food for human consumption.
These hazards were perceived as the greatest threat to public
health. In April 2007, the eight UEMOA countries (Benin, Burkina-
Faso, Cote d’Ivoire, Guinea-Bissau, Mali, Niger, Senegal and Togo)
adopted regulation 07/2007/CM/UEMOA concerning plant,
animal and food safety in the UEMOA area . More recently,
in 2010 and 2011, two training sessions were held in Benin to
familiarize these countries with the theoretical framework for
health risk analysis . Yet, there have been very few studies
on antimicrobial residues affecting food safety . However, in
developing countries, failure to respect waiting periods  leads
to high exposure to antimicrobial residues .
Drug in animals can be used as therapeutic, prophylactic
and growth promotion. Therapeutic use refers to the treatment
of established infections whereas prophylaxis is the use of drugs
either in individual or groups to prevent the development of
infections. Growth promoters (GPs) are any antimicrobial agents
administered at low or sub therapeutic dose to destroy or inhibits
growth of microbe which reduce the yield of food animals. The use
of antimicrobials as feed supplements can promote the growth
of food animals and also enhance feed efficiency. The uses of GPs
are resulting in meat of better quality with less fat and increased
protein contests . The use of drugs in food animals is
fundamental to animal health and well-being and to the economics
of the industry. There are five major classes of drugs used in food
animals: (1) topical antiseptics, bactericides, and fungicides
used to treat surface skin or hoof infections, cuts, and abrasions;
(2) ionophores, which alter rumen microorganisms to provide
more favorable and efficient energy substrates from bacterial
conversion of feed and to impart some degree of protection
against some parasites; (3) steroid anabolic growth promoters
(for meat production) and peptide production enhancers (bovine
somatotropin for increased milk production in dairy cows); (4)
antiparasite drugs; and (5) antibiotics as used to control overt and
occult diseases, and to promote growth  (Figure 2).
The medicinal products containing antimicrobials authorized
for veterinary use are those that have passed the marketing
authorization process of the competent national authority. After
an evaluation of the scientific data proving the efficacy of the
product and its safety for humans, animals and the environment the Competent Authority authorizes its importation, distribution
and use. No medicinal product may be marketed unless it has
first been authorized by the Competent Authority. However,
there are huge shortcomings in the implementation because
the technical evaluation of a marketing application is limited to
an administrative procedure alone especially in most African
Prohibited antimicrobials are substances for which it is not
possible to determine the Maximum Residue Level (MRL). Chloramphenicol,
dimetridazole, ipronidazole, nitroimidazoles, furazolidone,
nitrofurazone, and fluoroquinolones are prohibited for
extra-label use in food-producing animals . Chloramphenicol
is a broad-spectrum antimicrobial against Gram-positive and
Gram-negative bacteria. It was not possible to determine an MRL
based on the available data. The inability to set a threshold value
and shortcomings in the marketing authorization application led
to chloramphenicol being classified in 1994 as a prohibited substance
for use in food-producing animals. Dapsone, which is used
to treat leprosy in humans, is not authorized for use in food-producing
animals in Europe because of insufficient toxicology data,
making it impossible to determine the acceptable daily intake
(ADI) . In the year 1995 European Union (EU) prohibited the
use of nitrofurans for the treatment of bacterial diseases in livestock
production, due to concerns about the carcinogenicity of
their residues in edible tissue . In subsequent years Australia,
USA, Philippines, Thailand and Brazil also prohibited the use of
nitrofurans in food animals  (Table 1).
Veterinary drugs are generally used in farm animals for therapeutic
and prophylactic purposes and they include a large number
of different types of compounds which can be administered in the
feed or in the drinking water. The great majority of residues found
in edible tissues of animals have their source at the farm of origin.
In some cases, the residues may proceed from contaminated animal
feedstuffs. By far the most common cause of residues is the
failure to observe the proper withholding period following treatment
Human health risk can result from the presence of residues
of veterinary drugs and/or their metabolites in edible organs and
tissues of treated animals, in particular residues in concentrations
exceeding the MRL established by Council Regulation 2377/90
. Occurrences of veterinary drug residues pose the broad
range of health consequences in the consumers. The residues of
antibacterial may present pharmacological, toxicological, microbiological
and immunopathological health risks for humans .
Anthelmintics, such as benzimidazoles and probenzimidazoles,
are veterinary drugs used against endoparasites for the
prevention of animal infestations caused by nematodes, cestodes
and trematodes in food producing animals. Among the most
popular benzimidazoles are Albendazole (ABZ) and Mebendazole
(MBZ) . Benzimidazoles (BZDs) such as albendazole (ABZ),
fenbendazole and thiabendazole are a kind of broad-spectrum
veterinary drugs for prevention and treatment of helminthic
parasites in domestic animals. When BZD drugs were fed to
domestic animals, they were metabolized and then converted into
other compounds in vivo. Thus, these BZDs and their metabolites
can be left inedible animal foods or exist in the environment for a
period of time. The harmful BZDs and their metabolites residues
in some foods lead to a series of toxic effects such as congenic
malformations, teratogenicity, diarrhea, pulmonary edemas,
polyploidy, and necrotic lymphoadenopathy . Febantel (FEB)
is a probenzimidazole with which is further metabolized in vivo to
Fenbendazole, a benzimidazole anthelmintic also  (Table 2).
Disease status: The disease status of an animal can affect
the pharmacokinetics of drugs administered, which 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. For example, cattle
with acutely inflamed mastitis quarters, apramycin penetrates
these areas of the body, and concentrations of the drug have been
observed at ten times over the level recorded from cows without
Extra-label drug use: Extra-label drug use (ELDU) refers to
the use of an approved drug in a manner that is not in accordance
with the approved label directions. It occurs when a drug only
approved for human use is used in animals, 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, or the use of
drugs at levels in excess of recommended dosages. For instances,
the use of enrofloxacin solution as a topical ear medication
(Only approved for use as an injection) are the common ELDU in
veterinary medicine .
Improper Withdrawal Time: Improper withdrawal time is
another risk factor; the withdrawal time is the time required for
the residue of toxicological concern to reach safe concentration
as defined by tolerance. Based on the drug product, dosage form,
and route of administration it may vary from few hours to days or
weeks. It is the interval from the time an animal is removed from
medication until permitted time of slaughter for the production of
Acceptable daily intake: Acceptable daily intake (ADI) is the
amount of substance that can be ingested daily over a lifetime
without appreciable health risk. The evaluation of the safety of
residues is based on the determination of the ADI on which in turn
maximum residues limits (MRL) is based. The ADI is determined
by consecutive estimate of a safe ingestion level by the human
population on the lowest no effect level of toxicological safety
studies . If the drug is not a carcinogen, the no observed effect
level (NOEL) of the most sensitive effect in the most sensitive
species divided by a safety factor is used to determine an ADI for
drug residues. The FDA will calculate the safe concentration for
each edible tissue using the ADI, the weight in kg of an average
adult (60 kg), and the amount of the product eaten per day in
grams as follows; Safe concentration = [ADI (μg/kg/day) x 60 kg]
/[Grams consumed/ day].
Maximum residue level: A tolerance level (or maximum
residue levels, MRLs) is the maximum allowable level or concentration of a chemical in feed or food at a specified time of
slaughter or harvesting, processing, storage and marketing up to the
time of consumption by animal or human . The MRL in various
foodstuffs (muscle, liver, kidney, fat, milk and eggs) is determined
to minimize the risk of consumer exposure, considering dietary
intake. Such considerations as food technology, good farming
practices and the use of veterinary medicinal products may also
be considered when setting the MRL .
Calculating Withdrawal Period: The withdrawal period is
determined when the tolerance limit on the residue concentration
is at or below the permissible concentration. Withdrawal times are
determined in edible, target tissues. Most commonly, they are liver
or kidneys as they are primary organs of elimination and typically
display a residue for the longest time. During withdrawal studies,
the target organ is determined and animals are sampled at various
times after drug administration is stopped. For those drugs for
which only a kidney or liver tolerances has been established, if a
violative residue is found in the target organ, the whole carcass
would need to be discarded. On the other hand, for the drugs for
which a muscle tolerance has been established, even if a violative
residue is found in the kidney or liver a violative residue is not
found in the muscle, the carcass would not need to be discarded
Screening Test: 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 .
Advantage of these methods is that they have a wide detection
spectrum; they are simple to carry out and cheap; and can be used
for the screening of a large number of samples;  Possibility
of automatization; Reduced time to obtain the result; Good
sensitivity and specificity and Detection capability with an error
probability (b) < 5% . This method includes a large variety
of detection methods, ranging from physico-chemical analysis or
immunological detection to microbiological method .
The immunological methods are based on the interaction of
antigen-antibody which is very specific for a particular residue.
The most usual technique consists in the enzyme linkedimmunosorbent
assay (ELISA) and the detection system is usually
based on enzyme-labeled reagents. There are different formats
for antigen quantification like the double antibody or sandwich
ELISA tests and direct competitive ELISA tests . ELISA kits
are allowing the analysis of a large number of samples per kit,
do not require sophisticated instrumentation, the results are
available in a few hours and are quite specific and sensitive. It
has good performance for the analysis of antibiotic residues in
meat like tylosin and tetracycline , chloramphenicol ,
nitroimidazoles  and sulphonamides  and also for
Microbial inhibitions 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 . A plate test consists of a layer of
inoculated nutrient agar, with samples applied on top of the layer,
or in wells in the agar. Bacterial growth will turn the agar into an
opaque layer, which yields a clear growth-inhibited area around
the sample if it contains antimicrobial substances
Different types of biosensors have been developed in recent
years as an alternative approach to screen veterinary drugs
in meat. In general, these sensors usually contain an antibody
as a recognition element that interacts with the analyte. The
resulting biochemical signal is measured optically or converted
into an electronic signal that is further processed in appropriate
equipments . Biosensors can be able to detect simultaneously
multiple veterinary drugs residues in a sample at a time . In
general, these sensors are valid for control laboratories because
they can detect multiple residues in one sample and can thus
allow the analysis of a large number of residues and samples .
The next step after initial screening consists in the
unambiguous identification and confirmation of the veterinary
drug residues in foods of animal origin. The full procedure and
the methodologies for confirmatory analysis are costly in time,
equipment’s and chemicals. In addition, they require trained
personnel with high expertise . Different analytical techniques
are available for such purpose. When the target analyte is clearly
identified and quantified above the decision limit for a forbidden
substance or exceeding the maximum residue limit (MRL) in the
case of substances having a MRL, the sample is considered as noncompliant
(unfit for human consumption). Identification is easier
for a limited number of target analytes and matrices of constant
composition . Some examples of the available confirmatory
methodologies are as follows: The use of HPLC-electrospray
ionization (ESI) tandem mass spectrometry  or liquid chromatography-mass spectrometry with atmospheric pressure
chemical ionisation (APCI) .
ESI technique facilitates the analysis of small to relatively
large and hydrophobic to hydrophilic molecules and is thus very
adequate for the analysis of veterinary drug residues  even
though it is more sensible to matrix effects than APCI ionization
. ESI and APCI interfaces are the sources of choice to promote
the ionization of antibiotics and both complement each other well
with regards to polarity and molecular mass of analytes .
Drugs used in food animals can affect the public health
because of their secretion in edible animal tissues in trace
amounts usually called residues. For example, oxytetracycline
 and enrofloxacin residues  have been found above the
maximum residual level in chicken tissues. Similarly, diclofenac
residues were reported to be the cause of vulture population
decline in Pakistan .
Allergic Reactions: Drug hypersensitivity is defined as an
immune mediated response to a drug agent in a sensitized patient,
and drug allergy is restricted to a reaction mediated by IgE. An
allergic or hypersensitive effect following administration of a
drug (i.e., drug allergy is quite similar to that typified by allergic
response to protein, carbohydrate, and lipid macromolecules.
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 . Certain macrolides may
also in exceptional be responsible for liver injuries, caused by a
specific allergic response to macrolide modified hepatic cells [64
Mutagenic Effects: The term mutagen is used to describe
chemical or physical agents that can cause a mutation in a DNA
molecule or damage the genetic component of a cell or organisms.
Several chemicals, including alkalizing agents and analogous of
DNA bases, have been shown to elicit mutagenic activity  that
may have adversely affected human fertility .
Carcinogenic Effects: The term carcinogenic refers to any
substance or an agent capable of altering the genetic makeup
of an organism so that they multiply and become rancorous
while carcinogen refers to any substance that promotes
carcinogenesis, the formation of cancer or having carcinogenic
activity. Carcinogenic residues functions by covalently binding
intracellular components including DNA, RNA, proteins, glycogen,
phospholipids and glutathione . The ban of Diethylstilbestrol
(DES), a hormone-like compound used for food producing animals,
was as a result its strong carcinogenic effect.
Teratogenic Effect: The teratogen applies to chemical agents
that produce a toxic effect on embryo or fetus during a critical
phase of gestation. Of the anthelmintic, benzimidazole is embryo
toxic and teratogenic when given during early stage of pregnancy
because of the anthelminthic activity of the drug .
Disruption of Normal Intestinal Flora: The normal Intestinal
Flora is essential to human health. Not only does the symbiosis
exist to contribute to nutrient absorption  it also obstructs
and inhibits pathogen invasion, as well as aids in the development
and optimal functioning of the host immune system . The
bacteria that usually live in the intestine act as a barrier to prevent
incoming pathogenic bacteria from becoming established and
causing disease  by producing antimicrobial substances (such
as bacteriocins), altering luminal pH, and directly competing
against pathogens for nutrients. In addition, commensal bacteria
promote angiogenesis and the development of the intestinal
epithelium . Antibiotics might reduce total numbers of these
bacteria or selectively kill some important species when consumed
in food which contain their residues .
Development of Antimicrobial Resistance: Indiscriminate
use of veterinary drugs, mainly antimicrobials, anthelmintics,
and acaricides in food animals also play a major role in the
development of antimicrobial resistance (AMR) which has put
the public health at risk . This problem is further worsened
by irrational use through free access to prescription drugs and
their administration at sub-therapeutic concentrations for a long
period of time. Such conditions favor the selection and spread
of antimicrobial resistant strains in animals, environment and
humans . The consequences of antimicrobial resistance in
bacteria causing human infections include increased number
of infections, frequency of treatment failures and severity of
infection, and finally increased costs to society associated with
disease. Increased severity of infection includes prolonged
duration of illness and increased frequency of bloodstream
infections, hospitalization, and mortality .
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 that magnifies the problem of
misuse of anthelmintic agents . 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 . The ongoing threat of antibiotic
contamination is one of the biggest challenges to public health that
is faced by the human population worldwide . Such residues
are spreading rapidly, irrespective of geographical, economical, or
legal differences between countries.
In Ethiopia, as the study conducted from March 2016 to
June 2016 in University of Gondar veterinary clinic revealed,
anthelmintic drugs are quite commonly but improperly utilized
in the clinic. Three group of anthelmintics namely benzimidazoles
(Albendazole, fenbendazole, mebendazole and triclabendazole),
imidazothiazole (tetramisole and levamisole) and macrocyclic
lactone (Ivermectin) were used. Utilization of limited group of drugs for a long period may favor the development of resistance
which is risk factor for drug residues . Though the primary
purpose of veterinary drugs is to safeguard the health and welfare
of animals , 44.3% 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 a right drug and to make the treatment broader
anthelmintics can be given in combination with other drugs .
There also other study conducted in this country in 2007
indicated that the proportion of tetracycline levels in beef; the
study focused on the Addis Ababa, Debre Zeit and Nazareth
slaughterhouses. 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 82.1% tested
positive for oxytetracycline respectively. 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 .
Ethiopia is confronted with a number of problems associated
with unsafe handling of pesticide distribution and use. Most
pesticides used in Ethiopia are imported by international
manufacturing companies represented by local agents .
Currently, pesticide use practices are changing as a result of
the government plan to intensify and diversify agriculture by
promoting high value export crops such as flowers and vegetables.
For instance, more than 212 types of pesticides with different
active ingredients are being used to cultivate roses in Ethiopia.
But also, small holders growing vegetables are facing challenges
because they are usually resource-poor but also risk averse and
under these conditions it is challenging to decide when, how, how
much and which pesticide to apply among the hundreds available
on the market .
Herbicides are widely used in agricultural crops to control
weed. Their introduction in the food chain via the environment
can be considered a risk for human health due to the toxicity of
the most of these compounds. In addition, herbicides are relatively
long-lived in the environment, and can be accumulated by means
of food chain amplification. Due to their extensive use in cultivation
of crops (e.g. soybean, wheat, maize) and relatively stable nature
in environments, the residues of herbicides were frequently
detected in soil, cereal grain and water. To ensure human food
safety, the United State (US), and the European Union (EU) have
set maximum residue limits (MRLs) for some herbicide residues
in soybean, corn and wheat in the range 0.01-2mg/kg, depending
on the particular grain matrix and herbicide, but without the MRL
for most herbicides .
Use of synthetic acaricides is the primary method of tick
control. Synthetic insecticides particularly organophosphates,
carbamates, pyrethroids and neonicotinoids have been extensively
used by farmers for protecting medicinal and aromatic plants.
Consequently, toxic residue of pesticides in raw material posed
serious concerns of risk to human health. Therefore, an integrated
management including cultural practices, plant-derived products
and biological control has been experimented on limited scale
The European Union has strictly regulated the use of veterinary
drugs in food animal species. Some of these drugs can be permitted
only in specific circumstances (therapeutic purposes) but under
strict control and administration by a veterinarian . The use
of substances having hormonal or thyreostatic action as well
as b-agonists is controlled by official inspection and analytical
services following Commission Directive 96/23/EC on measures
to monitor certain substances and residues in live animals
and animal products. This Directive contributed to a sensible
reduction in the number of growths promoting reported cases.
However, laboratories in charge of residues control usually face a
large number of samples with great varieties of residues to search
in short periods of time making it rather difficult. The availability
of simple and useful screening techniques is really necessary for
an effective control .
Establishment of a legislative framework and of an institutional
structure is the first step in the assessment and management of
drug-related risk. From this point of view, according to pending
European legislation the use of veterinary drugs must be based
on risk evaluation. The risk due to the use of veterinary drugs
is “any risk for animal or public health relating to the quality,
safety and efficacy of the veterinary medicinal product and any
risk of undesirable effect on the environment”. Risk management
is a task of both private and public veterinary services that are
involved in the prevention and control of all hazards arising
from the use of veterinary drugs. A major tool for veterinarians
to prevent and control drug-borne risk is “pharmacovigilance”
. Pharmacovigilance is the post-marketing surveillance of
veterinary drug and vaccine safety used for prevention, diagnosis
and therapy and consists of the report of any adverse effects of
a drug by veterinarians, pharmacists, farmers and other health
care professionals, in the improvement of knowledge about the
pharmacological action of a drug and hence, in the evaluation of
the risk/benefit balance of a drug .
The main tasks of pharmacovigilance can be summarized as
a. Control of clinical safety of veterinary medicinal
b. Control of potential reaction in man linked to user safety;
c. Evaluation of decreased efficacy or lack of expected
activity of a veterinary medicinal product;
d. Control of maximum residue levels (MRL) of veterinary
drugs in food products of animal origin;
e. Assessment of risks for the environment related to the
use of veterinary drugs;
f. Control of the development of drug resistance, with
particular concern to antibiotic resistance .
The control of parasitic helminths in domestic animals relies
largely on the use of anthelmintic drugs. But inappropriate
and indiscriminate use of anthelmintic leads to the emergence
of anthelmintic resistance, treatment failure and increase in
mortality and morbidity . Most failures during anthelmintic
therapy may occur when the parasite is unknown and anthelmintic
drugs are administered empirically. To avoid these problems,
it is important to apply confirmatory diagnosis and selection of
the right anthelmintic . Maximum Residue Limits (MRLs) in
certain products of animal origin, including meat and milk have
been established by the European Union. The need for more
intensive residue controls becomes stronger considering several
studies which indicate that benzimidazoles are not degraded after
microwave and oven-baking, storage at -18 ℃ for three to eight
months and after cooking. However, no major losses for residues of
ABZ, MBZ or FBZ, after roasting of meat and liver (40min at 190 ℃)
or shallow frying (muscle 8-12 min, liver 14-19min) in a domestic
kitchen . Consequently, conventional cooking hardly protects
consumers against the ingestion of residues of anthelmintic
veterinary drugs in these foods. Accordingly, the estimation of
residues intake through certain food items consumption becomes
a necessity to ensure that the Acceptable Daily Intakes (ADIs) of
the drugs are not exceeded [92-95].
Irrational use of drugs in veterinary medicine as well as the
need for control of their use becomes even bigger problem when
used on food producing animals. In this case, there is the possibility
that minimal quantities of drugs and their metabolites (residues)
which remain in edible tissues or in animal products (meat, milk,
eggs, honey) induce certain harmful effects in humans as potential
consumers of such food . When drugs are used to improve
the productivity of food animals that are intended for human
consumption, then there is possibility for producing adverse
effects on humans. To prevent this risk, it is necessary to use drugs
rationally, i.e., to use them only when they are really indicated, in
the right way, at the right time, in the right dose and respecting
withdrawal period. The residue control strategy is based on a twostep
approach: (1) the detection of residues using sensitive tests
with a low rate of false negatives; (2) followed by confirmation,
requiring quantification against the MRL and identification with a
low rate of false positives. Hence, the residue prevention strategy
is based on preventing entry of violative residues in food of animal
origin intended for human consumption by proper drug use
guide developed for use by both veterinarians and food animal
producers include the following:
a. Herd health management; Drug residues are best
avoided by implementing management practice and herd
health program that keep animals healthy and producing
b. Use of approved drugs.
c. Establishment of valid veterinarian-client-patient
relationship; the use of prescription drug and the ELU
necessitate a veterinary-client patient relationship.
d. Proper drug administration and identification of treated
animals; before administering or dispensing drugs one has to
know the drugs approved for all classes of cattle on the farm
and be familiar with approved dosage, route of administration,
and withholding time.
e. Proper maintenance of treatment records and
identification of treated animals.
f. Creating awareness of proper drug use, and methods to
avoid marketing adulterated products principally educational,
total residue avoidance program is based upon the objective of
improving the livestock producer’s management and quality
control of marketing animals with emphasis on avoidance of
Although the veterinary drugs have played a great role in
control and prevention of disease in animals and promote the
growth of food animals, its use is associated with problems such
as development of resistance and residue effects in food animals.
These adverse effects are generally due to irrational use of drugs
such as misuse, extensive use, failure to keep strict adherence of
withdrawal and withholding time of drugs. The development of
resistant microorganisms in animals and the presence of drug
residue in food of animal origin have significant effect on public
health. Globally, more than half of all medicines are prescribed,
dispensed or sold improperly. Many livestock producers treat their
animals by themselves. The uncontrolled use of anti-infectious
agents can lead to residues in animal products. The risks of
residues in foodstuffs of animal origin could be reflected into
several forms of adverse effects. The great majority of residues
found in edible tissues of animals originated in farms but, some
cases may proceed from contaminated animal feedstuffs. By far
the most common cause of residues is the failure to observe the
proper withholding period following treatment. In general, when
various types of veterinary drugs; antimicrobials, antiparasitic
and β-agonists, food additives, Industrial and agricultural
products; pesticide, acaricide, herbicides etc. are used in food
producing animals intended for human consumption and in the
environment indiscriminately and they pose a great public health
effect. Therefore, strict control measures to promote rational veterinary drug use have crucial importance on global economy
and public health.
Based on above conclusions the following recommendations
a. The government should regulate irrational and
unauthorized use of drugs and, implement residue control
strategy such as management practice and herd health
program that keep animals healthy and producing efficiently
to avoid drug residues,
b. Improperly prescribed, dispensed and sold drug should
c. Proper maintenance of treatment records and
identification of treated animals should be implemented,
d. The withdrawal time should be appropriately protected,
e. Creating awareness of farmers, consumers and health
professionals about drug residues and its public health
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