Food Toxicology

(Course code-BND253A)

Topic: Growth hormones

and veterinary drug residues
in foods
06/19/2025 1
 What are growth hormones??
• Growth hormone (GH) also known as human
growth hormones (hGH or HGH) in its human
form, is a peptide hormone that stimulates
growth, cell reproduction, and cell
regeneration in humans and other animals.
• It is important in human development since
it stimulates production of IGF-1 and
increases the concentration
of glucose and free fatty acids.
 Contd..
• Secretion of growth hormone in the pituitary
is regulated by the hypothalamus.
• It has anabolic function in the body.
• It is particularly associated with muscle and
bone growth.
• Growth hormone has considerable potential
as an anabolic agent in animal production.
 Contd..
• For example, pigs treated with GH will grow
faster (i.e. deposit protein), require less feed
per unit of body weight gain, and will have
less carcass fat than untreated animals.
• Lactating cows will produce more milk with
less feed.
• Growth hormone is also used in plants but
plant growth substances are also produced by
plants and are referred to as phytohormones.
 Growth hormone in plants
• Growth hormones initiate biochemical processes
which help in increased production of roots, shoots,
flowers, etc.
Types include:
• Auxin
• Gibberellins
• Cytokines
• Ethylene
• Inhibitors
• Growth retardants
 Veterinary drug
• Veterinary drugs are used for therapeutic and
prophylactic purposes in animals to regulate
infections of bacterial and prevent outbreaks
of animal diseases.
• Antibiotics are an example of veterinary
drugs used to enhance animal health and
development.
• The use of veterinary drug has increased
since
 Contd..
are critically needed to meet the challenges of
providing adequate amounts of food for the
growing world population.
• This is also the case as these drugs improve
the rate of weight gain, improve feed
efficiency, or prevent and treat diseases in
food producing animals.
• However it is of great concern in present
scenario.
 Drugs used in veterinary clinics are;
• Antibiotics: Oxytetracycline, Quinolones
• Anti-inflammatory: Analgin
• Anesthesia drugs and sedatives: Atropine sulfate
• Hormones: oxytocine, estradiol cypionate
• Vitamins and trace elements: oligovit
• Digestion drugs: laxavet
• Diuretics: Furosemide, mannitol
• Ointments: iodine, zinc ointment
 Residues
• As defined by the European Union and d the
Center for Veterinary Medicine, “residues are
pharmacologically active substances (whether
active principles, recipients or degradation
products) and their metabolites which remain
in foodstuffs obtained from animals to which
the veterinary drugs has been administered”.
• Most drugs are metabolized in order to
facilitate elimination and detoxification.
 Contd..
• In general, most of the parent product and its
metabolites are excreted in urine and a lesser
extent via feces.
• However, these substances may also be found
in milk and eggs, and in the meat obtained
from those animals.
• Rationally, there is no product coming from a
treated animal should be consumed unless the
entire drug administered has been eliminated.
 Contd..
• However, because of the improvement of
analytical techniques, which meant that the
value of zero became smaller and smaller that
depicts the limits corresponding to the
sensitivities of parts per million (ppm), parts
per billion (ppb) and parts per trillion (ppt).
• There are nearly always detectable residues,
but such residues are at an extremely low
concentration and they are not inevitably toxic.
 How veterinary drug residues comes to
food:
• Not following recommended label directions
or dosage (extra-label usage);
• Not adhering to recommended withdrawal
times;
• Administering too large a volume at a single
injection site;
• Use of drug-contaminated equipment, or
failure to properly clean equipment used to
mix or administer drugs
 Contd..
• Dosing, measuring, or mixing errors;
• Allowing animals access to spilled chemicals or
medicated feeds;
• Animal effects- age, pregnancy, congenital,
illness, allergies;
• Chemical interactions between drugs
• Environmental contamination;
• improper use of agricultural chemicals such as
pesticides
 Accumulation of these residues
• They usually accumulate in the liver or kidney
rather than other tissues.
• It has been noted that different residue levels
can be found in different tissue positions
such as site and route of administration.
 Risk factor for residue development
• Age of animal- Weaning status and, to a
lesser extent, the age of the animal affect
drug disposition.
• For example: Calves fed grain had shorter
clearance times (approximately four days) for
sulfamethazine than unweaned calves.
• The elimination half-life of tindazole is
shorter in unweaned calves than in adult
cows.
 Feeding
• Diet can affect the bioavailability of drugs.
• A research carried out for a drug named
Fenbendazole on buffalo fed with dried hay or
fresh green herbage showed that animals
receiving feed containing fresh herbage had
lowered bioavailability of the drug as it is
progressively released with digesta, and the
presence of fresh herbage increases gut activity
and the flow rate of digesta and depletes the
drug.
 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 or when the presence of infection
and/or inflammation causes the drug to accumulate
in affected tissues.
• Ketoprofen levels in milk increase during clinical
mastitis where there is an influx of serum
components into the udder.
 Pharmacokinetics
• The term pharmacokinetics refers to the
movement of drug into, through and out of
the body: the time course of its absorption,
bioavailability, distribution, metabolism, and
excretion.
• Absorption: It is described as the process,
which a compound passes from its site of
administration into the bloodstream.
 Distribution
• Нere are four major factors responsible for
the extent and rate of distribution.
• These are the physicochemical properties of
the drug, the concentration gradient
established between the blood and tissue,
the ratio of blood flow to tissue mass, and
the affinity of the drug for tissue constituents
and serum protein binding.
 Metabolism (biotransformation)
• It is the principal mechanism of elimination for the
transformation of drugs or xenobiotics into
metabolites of the chemical reaction.
• Hepatocytes play an extremely important role in the
metabolism of drugs and xenobiotic-compounds that
are foreign to the body, some of which are toxic.
• The kidneys are responsible ultimately to dispose of
these substances, but for effective elimination, the
drug or its metabolites must be made hydrophilic
(polar, water-soluble).
 Withdrawal time
• The withdrawal time (also known as the
depletion or clearance period) is the time for
the residue of toxicological concern to reach
a safe concentration as defined by the
tolerance.
• Depending on the drug product, dosage form,
and route of administration, the withdrawal
time may vary from a few hours to several
days or weeks.
 Contd..
• It is the interval necessary between the last
administration to the animals of the drug
under normal condition of used and the time
when treated animal can be slaughtered for
the production of safe food stuffs.
 Risk assessment
• Risk assessments of veterinary drugs consist of
assessing their toxicological and microbiological
impacts and identifying acceptable consumption
levels that the compounds should not exceed.
• Toxicological impact implies any biological
adverse effects caused by direct intake of
veterinary drugs, such as body weight change,
immune suppression, and various disorders of
normal body function.
 Contd..
• For microbiological impact, the targets of the
ingested veterinary drugs are human intestinal
microflora rather than the human body.
• Microbiological impact needs to be evaluated
when the ingested residue compound is anti-
microbiologically active, not transformed
irreversibly to inactive metabolites, and enters
the lower intestine by any administration route.
 Risk assessment steps in food
• Risk assessments of veterinary drugs residing
in foods are performed by following the
integrative steps of:
Hazard identification,
Hazard characterization,
Exposure assessment, and
Risk characterization.
 Effect on public health
• Development of drug resistance
• Drug hypersensitivity reaction
• Carcinogenic effect
• Mutagenic effect
• Teratogenic effect
• Disruption of normal intestinal flora
 Development of drug resistance
• Resistant microorganism can get access to
human, either through direct contact or
indirectly via milk, meat, and or egg.
• As the bacteria of animal origin, they may
either colonize human endogenous flora or
superimpose and additional load to the
reservoir of resistance genes already present
in man.
 Contd..
• It has been documented that human develop drug
resistant bacteria such as Salmonella,
Campylobacter, and Staphylococcus from food of
animal origin.
• Examples of drugs that have been shown to cause
the growth of resistant bacteria in food of animal
are fluoroquinolones and avaoparin.
• Uses of penicillin, tetracyclines, and sulfa drugs; in
agriculture is suggested by the WHO to be a high
priority issue.
 Drug hypersensitivity reaction
• 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.
• 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
 Carcinogenic effect
• The potential hazard of carcinogenic residues
is related to their interaction or covalently
binding to various intracellular components
such as proteins, deoxyribonucleic acid
(DNA), ribonucleic acid (RNA), glycogen,
phospholipids, and glutathione.
• This results in changes of gene expression
and gene mutation which may initiate
abnormal cell proliferation causing tumors.
 Mutagenic effect
• 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.
• There has been increasing concern that drugs may
pose a potential hazard to the human population by
production of gene mutagen or chromosome breakage
that may have adversely affects human fertility.
 Teratogenic effect
• The term teratogen applies to drug or chemical
agent that produces a toxic effect on the embryo
or fetus during a critical phase of gestation.
• Anthelmintics and benzimidazole is embryo
toxic and teratogenic when given during early
stage of pregnancy.
• Benzimidazole drug of oxfendazole, has also
exhibited a mutagenic effect along with
teratogenicity.
 Disruption of normal intestinal flora
• The bacteria that usually live in the intestine acts
as a barrier to prevent incoming pathogen from
being established and causing diseases.
• Antibiotics may reduce the total number of the
bacteria or selectively kill some important
species.
• Drugs like, flunixin, streptomycin and tylosin in
animals, and vancomycin, nitroimidazole, and
metronidazole in humans are known for this
effect.
 Residue avoidance
• Half-life (t1/2) is the time it takes to remove 50%
of the drug from the animal and used to estimate
withdrawal time.
• A drug with a large volume of distribution (Vd)
generally has relatively good tissue distribution
compared with a drug of restricted distribution.
• The utility of viewing half-life as a function of the
Vd and clearance (CL) is that these two
independent parameters reflect the underlying
physiology of the animal.
 Control and preventive measure
• Residue control strategy is based on a two-
step approach:
The detection of residues using sensitive
tests with a low rate of false negatives;
Confirmation, requiring quantification against
the MRL and identification with a low rate of
false positives
 Contd..
• Hence, the residue prevention strategy is based
on preventing entry of violative residues in
meat or milk intended for human consumption
by proper drug use guide developed for use by
both veterinarians and food animal (dairy and
beef) producers include the following:
• Herd health management- clean and healthy
environment; (good nutritional to meet
growth, maintenance and lactation needs
 Contd..
• Use of approved drugs;
• Establishment of valid veterinarian-client-
patient relationship;
• Proper drug administration and identification of
treated animals;
• Proper maintenance of treatment records and
identification of treated animals;
• Having proper drug residue testing capabilities
really available on and off the farm