Transcript Lect. 6.ppt

Dr. Nayira A. Abdel Baky
Associate Professor
Pharmacology and Toxicology
-They are naturally present in plants and
animals.
-Natural toxins are not acutely toxic, except
in a few cases.
-Most of the natural toxins, particularly those
occurring in plant-derived foods, induce
adverse effects only after chronic ingestion.
General toxicity (instant death or illness)
Carcinogenic
Mutagenic
Teratogenic
Endocrine disrupters (hormones)
Microbial pathogens
Endogenous toxins of plant origin
-Toxic phenolic substances: flavonoids, tannins, coumarin,
safrole, and myristicin
-Cyanogenic glycosides
-Glucosinolates
-Acetylcholinesterase inhibitors
-Biogenic amines
-Central stimulants
Natural contaminants
-Mixing of edible plants with toxic plants
-Contamination resulting from intake of toxic substances by
animals
-Microbial food contaminants
Flavonoids
-The flavones group has been extensively investigated
for mutagenicity.
A well-known mutagenic representative is quercetin,
occurring, for example, in cereal crops. Quercetin
is the only flavonoid shown to be carcinogenic in
mammals after oral administration.
Tannins
Tannic acid, also known as gallotannic acid,
gallotannin, or simply tannin, has been reported to
cause acute liver injury, i.e., liver necrosis and
fatty liver
Safrole, coumarin, myristicin
Coumarin widely occurs in a number of natural
flavorings, that are extensively used in sweets and
liquors.
Safrole. It is found in black peppers.
-Both coumarin and safrole are still allowed for food
use in the European Community. They are prohibited
in the US though, as they have been found to cause
liver damage and liver tumors in rats.
Myristicin is found in spices and herbs such as nutmeg,
mace, black pepper, carrot, parsley, celery, and dill.
It has been suggested that myristicin contributes to the
toxicity of nutmeg. After nutmeg abuse, tachycardia,
failing salivation, and excitation of the central
nervous system have been reported. Nutmeg has
been abused as a narcotic.
-Cyanogenic glycosides are glycosides from which
hydrogen cyanide is formed on contact with stomach
acid . They can be found in food plants like
cassava, lima beans and the seed of some fruits
(e.g. peaches)  cyanide content.
-Fresh cassava cortex produces cyanide in quantities
ranging from 1.0 to more than 60.0 mg per 100 g,
depending on several conditions, including variety,
source, time of harvest and field conditions.
Cyanogenic glycosides
Jansenn, Put & Nout (1997)
-Glucosinolates are a particular group of substances,
occurring in cruciferous plants, such as cabbage
and turnips, cauliflower, brussel sprouts, broccoli,
turnip, radish.
-It inhibit the uptake of iodine by the thyroid iodine
deficiency.
-Concerning toxicity and antinutritive activity, the
hydrolysis products are the active agents, not the
glucosinolates themselves.
-Hydrolysis of glucosinolates results in the formation
of isothiocyanates and nitriles.
-Several isothiocyanates have been shown to be
embryotoxic in rats, while in vitro studies have
proved a number of them to be cytotoxic and
mutagenic. Meanwhile, several nitriles have been
identified as precursors of N-nitroso compounds
which are carcinogenic.
-Low molecular weight organic bases, which pose biological
activity.
-Naturally present in animals, plants and microorganisms.
-Sources: fermented foods, vegetables, meats .
-High concentration in fish and cheese.
-Legal upper limit:
- histamine: 100 mg/kg food
- tyramine: 100-800 mg/kg food
- phenyletylamine: 30 mg/kg food.
-The toxicity dose of BA depends on the individual sensitivity
and characteristic.
Biogenic amines
Jansenn, Put & Nout (1997)
There are three important sources for Natural
contaminants in food:
-Raw materials of plant origin can become
contaminated if they are mixed with toxic
non-nutritive plant species.
-Raw materials of animal origin, mainly fish and
milk, can also become contaminated if the
animal has ingested or contaminated with
toxic substances of natural origin.
-Contaminants of natural origin can be the
microorganism itself or the products of
microorganisms.
-Several intoxications have been reported
following the consumption of contaminated
cereals.
-Ex. Plants that contain pyrrolizidine alkaloids,
that cause acute liver damage and vein lesions.
These substances may also contribute to the
liver cancer incidence in humans.
i. Toxins Occurring in Animal Liver
-The animal liver is a nutritious protein-rich food.
-Animal livers produce toxic bile acids that could be
arranged in decreasing order of their toxicity into
cholic acid ˃ deoxycholic acid ˃ taurocholic acid.
-Toxicity could be appeared if animal livers
consumed in large quantities for long time.
-Pregnant women are not recommended to eat
animal livers for the potential toxicity of bile acids
and bioaccumulation of any toxic substances in the
animal liver.
ii. Algal Toxins Occurring in Marine Animals
Algal toxins are produced by several marine
phytoplanktons (e.g. cyanobacteria (blue-green
bacteria).
These marine toxins usually accumulated in fish and
shellfish present in the surrounding waters.
Humans can be exposed to these toxins through eating
contaminated seafood, skin contact, and even drinking
water.
Characters of algal toxins occurring in marine animal:
1- These toxins are highly toxic (even in picogram
doses).
2- Unlike many of the microbial toxins, algal toxins are
generally heat stable and, therefore, not altered by
cooking methods, which increases the likelihood of
human exposures and toxicity
Microbial-related foodborne diseases could be due
to either infections or intoxications.
o Infections diseases involving the pathogen
itself.
o Intoxications diseases involving the pathogen’s
toxic products (toxin, toxic metabolites).
General symptoms vary from acute gastroenteritis
(Nausea, vomiting, Diarrhea) to more serious
condition according to the causative
microorganism.
Treatments:
i. Gastroenteritis is self-limited, specific treatment is not
necessary.
ii. Supportive treatment includes adequate rehydration
and electrolyte supplementation that could be achieved
with either an oral rehydration solution (ORS) or
intravenous solutions (e.g., isotonic sodium chloride
solution, lactated Ringer solution).
iii. If symptoms persist beyond 3-4 days, the specific
etiology should be determined by performing stool
cultures.
iv. Till cultures are performed, empiric treatment with an
agent that covers the Shigella and Campylobacter
organisms is reasonable in those with severe diarrhea
with systemic signs.
v. A 3-day course of a fluoroquinolone (e.g., ciprofloxacin,
norfloxacin).
vi. TMP/SMX (Bactrim) is an alternative therapy.
-Aflatoxins are the most important mycotoxins, which is
produced by certain fungus species of Aspergillus (A.
flavus and A. parasiticus), which develop at high
temperatures and humidity levels.
-Aflatoxins are carcinogenic substances and may be
present in a large number of foods. This toxin can cause
cancer, cirrhosis of the liver.
-The most common commodities contaminated are tree nuts,
peanuts, and corn and cottonseed oil.
-The major aflatoxins of concern are B1, B2, G1, and G2 
usually found together in various proportions. Aflatoxin B is
usually predominant, and it is the most toxic and
carcinogenic
Mushroom is a fungus with high protein content.
Some types are edible, other are very toxic.
Toxic types of mushroom include:
1- Type containing phallotoxins and amatoxins.
o Phallotoxin causes GIT disturbances
o Amatoxin, interferes with protein synthesis
(inhibit RNA polymerase) causing hepatic,
renal and CNS effects.
2- Amanita muscaria producing muscarine.
3- A species producing the hallucinic agent
psilocybin
1. Polycyclic Aromatic Hydrocarbons (PAHs)
PAHs are strong carcinogenic compounds.
One of the most abundant food sources of
PAHs is:
A. Vegetable oil (present in several types of
foods like (vegetable margarine)
B. Charcoal broiling or smoking of food also
causes PAHs contamination (PAHs are formed
mainly from heating and melting of fats and
carbohydrates in foods at high
temperatures).
2.Maillard Reaction Products
The Maillard reaction of amino acids with
sugars occurs during a variety of food
processes, cooking, and in storage.
Some products formed are volatile with
strong odors.
Chronic exposure of these products in
processed foods exhibited strong mutagenic
and carcinogenic effects.
Oriental ways of cooking (like Egyptian
cooking) enhance formation of Millard
reaction products in food.
 3.
N-nitroso compounds (NOCs), N-Nitrosamines
& Nitosamide
These nitrogenous compounds are potent
carcinogens.
Sources of NOCs include several types of food
such as:
o Nitrate-cured meats and beverages such as malt
beverages.
o Nitrite and nitrates are used as intentional food
additive to fix the color of meats and inhibit
oxidation.
Food additives
A food additive is a substance or mixture of
substances that could be added to food
during production, processing, storage,
and/or packaging.
There are two categories of food additives:
1- Intentionally added food additives (Direct food
additives) that are purposely added to perform specific
functions. They include preservatives, antibacterial
agents, bleaching agents, antioxidants, sweeteners,
coloring agents, flavoring agents, and nutrient
supplements as vitamins.
2- Unintentionally food Additives (Indirect food additives)
that are incidentally be present in food in trace
quantities as a result of some phase of production,
processing, storage, or packaging. (e.g. pesticide
residues & industrial wastes)
These are group of food allergies and sensitivities
that can affect only a few people in the population.
EX.
A. Food hypersensitivity (allergy)
B. Anaphylactoid Reactions
C. Pharmacologic Food Reactions
D. Food Idiosyncrasy
E. Metabolic Food Reactions
A. Food hypersensitivity (allergy)
This food adverse reaction involves an immune-mediated
response.
Epidemiology:
Children appear to be the most susceptible to food allergy,
result from incomplete maturation of the digestive tract.
Pathophysiology:
Food hypersensitivity could be triggered by very small
amounts of food and usually occurs on second exposure or
to a cross reacting antigen.
The immune response to food is generally IgE-mediated
(immediate food hypersensitivity) and/or cell-mediated
(delayed food hypersensitivity).
Exercise-induced food allergy, curious type of food allergy,
is apparently provoked by exercise that has been
immediately preceded or followed by the ingestion of
certain foods including shellfish, peach, wheat, celery,
and "solid" food.
Chemistry of Food Allergens:
Most allergens (antigens) in food are protein in nature.
Treatment of Food Allergy:
1- Total avoidance of specific allergens
2- Supportive & symptomatic treatments include:
(Injection of rapidly acting corticosteroids + antihistaminics)
B.Anaphylactoid Reactions (Scombrotoxicosis)
They are non immune-mediated reactions, mimicking
anaphylaxis responses through direct ingestion of
food containing histamine (the primary mediator of
anaphylactic reactions).
The most clear example of food containing histamine is
Ingestion of scombroid fish (e.g., tuna, mackerel)
that have been spoiled by some microorganisms
(e.g: E-coli, Salmonella spp., and Shigella spp.).
Putrefaction of these fish leads to release of
histamine (up to 90 mg/ fish).
Symptoms include itching, chronic urticaria,
angioedema, exacerbation of atopic eczema,
rhinitis, bronchial obstruction, asthma, diarrhea
and other intestinal disturbances, and vasomotor
headaches.
C. Pharmacologic Food Reactions
These adverse reactions are characterized by
exaggerated responses to pharmacologic agents
in food, also called "false food allergies".
These reactions are associated with receptor
anomaly.
D. Food Idiosyncrasy
It is a quantitatively abnormal response to a food substance
or additive but without involvement of immune responses.
It depends on genetic makeup of affected individuals
E. Metabolic Food Reactions
These food reactions are distinct from other categories
of adverse reactions in that the foods are more or less
commonly eaten and demonstrate toxic effects only
when eaten in excess amount (as a result of abnormal
desire for a specific food) or improperly processed
food.