Transcript final toxi presentation

Toxicology
WHAT IS TOXICOLOGY?

Toxicology is the study of how natural and man made poisons
cause undesirable effects in living organisms.
Harmful Effects of Toxicology
 It may damage the survival or normal functions of an individual.
What is Toxicity?


1.
2.
3.
4.
The degree to which a substance is poisonous or can cause injury.
The toxicity depends on a variety of factors.
Dose
Duration
Route of Exposure
Shape and structure of the chemical itself
What is Toxicant?
A toxicant is any chemical that can injure or kill humans, animals or
plants.
 Toxicant is the term used when talking about toxic substances that are
produced by or are a by product of man-made activities.

What is a Toxin?

The term toxin is used when a toxic substance is produced
naturally(phytotoxin, zootoxin or bacteriotoxin) OR synthetic chemicals
that alter the growth, development or kill the organism
Toxic Symptom

Any sign or feeling that represents or indicates the presence of a poison
in the system
Toxic Effect/Poisonous Effect

Health effects that occur due to exposure to a toxic substance
Selective Toxicity

Means that a chemical/toxin will produce injury to one kind of living
matter without harming another form of life, even though the two may
exist close together
TYPES OF TOXIC EFFECT
How Does Toxicity Develop?
Before toxicity can develop a substance must come in contact with the
body surface or respiratory tract.
 The dose or amount of a toxin also matters a lot in this case

Dose
Actual amount of a chemical that enters the body
 Dose received may be due to either Acute Exposure or Chronic
Exposure



Acute Exposure(occurs over a short period of time, usually 24 hours)
Chronic Exposure(occurs over long period of time such as weeks,
months or years)

The amount of exposure and the type of toxin will determine the toxic
effect.
Dose–Response Curve
 Direct relationship between exposure and health effect.
 Greater is the exposure worst is the effect on human/living things
Threshold Dose
 The lowest amount of exposure or dose at which no adverse effects can
be seen in population
FIELD OF TOXICOLOGY
Sub
disciplines of toxicology
 Environmental
Toxicology
(study of effects of pollutants on living organisms, populations, ecosystem
and the biosphere)
 Regulatory
Toxicology
(use of scientific data to decide how to protect humans and environment
from excessive risks)
 Clinical
Toxicology
(deals with the prevention, diagnosis and treatment of different
poisoning cases)
• Food Toxicology
(study of the nature, properties, effects, and detection of toxic
substances in food, and their disease manifestation in humans)
• Forensic Toxicology
(deals with the study of chemical analysis to determine the cause
and circumstances of death and postmortem investigations)
NATURAL TOXINS:
 Naturally
 Usually,
present in plants & animals
natural toxins are not acutely
toxic, except in a few cases in animals.

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 toxins
ENDOGENOUS TOXINS OF PLANT ORIGIN
1. Flavonoids:






A class of plant pigments that are widely present in human food.
These pigments are polyhydroxy-2-phenylbenzo-γ-pyrone derivatives,
occurring as aglycones, glycosides and methyl ethers.
A group of yellow pigments that occurs abundantly is the flavones.
Examples
 nobiletin,
 tangeretin (in citrus fruits) and
 3, 3′, 4′, 5 ,6 ,7, 8-heptamethoxyflavone (in grapefruit).
The flavones are generally located in the oil vesicles of the fruit peel.
Flavones are non-polar, and therefore readily soluble in the oil.
They can be found in the juice after pressing the peel.
2. Tannins:


1.
2.



Tannins are a heterogeneous group of broadly distributed
substances of plant origin.
Two types of tannins can be distinguished on the basis of
degradation behaviour and botanical distribution:
hydrolysable tannins and
condensed tannins.
The hydrolysable tannins are Gallic, digallic, and ellagic acid
esters of glucose or quinic acid.
Example: tannic acid, also known as Gallo tannic acid, Gallo
tannin, or simply tannin.
Tannic acid has been reported to cause acute liver injury, i.e.,
liver necrosis and fatty liver.
3. Goitergens:







Glucosinolates are a particular group of substances,
occurring in cruciferous plants, such as cabbage and
turnips. They can be considered as natural toxins,
but also as antinutritives.
Presents in many commonly consumed plants, such
as cabbage, cauliflower, Brussels sprouts, broccoli,
turnip, radish, oil seed meals.
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.
The enzyme becomes available for catalysis when
cells are damaged on cutting or chewing.
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.
4. Safrole, coumarin, myristicin
5. Mushroom Toxins
 Some other natural toxins:
Biogenic amines, Acetyl cholinesterase inhibitors,
Cyanogenic glycosides,
NATURAL CONTAMINANTS:


Natural contaminants can also originate from biological systems different
from those in which they occur.
There are three important sources:
 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 toxic substances of natural
origin.
 Contaminants of natural origin can be the products of
microorganisms.
NATURAL TOXINS IN AQUATIC ORGANISMS




Paralytic shellfish poisoning (PSP) is attributed to the
consumption of shellfish that have become contaminated
with a toxin or group of toxins from the ingestion of toxic
plankton, in particular toxic dinoflagellates.
The shellfish involved are pelecypods, a family of
mollusks, including mussels and clams.
The dinoflagellates produce a complex mixture of toxins.
One of the components has been identified as saxitoxin.
Shellfish poisoning symptoms:
tingling and burning in face, lips, tongue, and ultimately the
whole body, and parathesia followed by numbness, general
motor incoordination, confusion, and headache
 These symptoms develop within 30 minutes after ingestion.
Death, preceded by respiratory paralysis, occurs within 12
hours.

MYCOTOXIN
Mycotoxins are secondary metabolites of fungi which can
induce acute as well as chronic toxic effects (i.e.,
carcinogenicity, mutagenicity, teratogenicity, and
estrogenic effects) in animals and man.
 Currently, a few hundred mycotoxins are known, often
produced by the genera Aspergillus, Penicillium, and
Fusarium.
 Toxic syndromes resulting from the intake of mycotoxins
by man and animals are known as mycotoxicoses.
 Because of their chemical stability, several mycotoxins
persist during food processing, while the molds are killed.

AFLATOXINS






Aflatoxins are the most important mycotoxins, which is produced by
certain 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.
For substances of this type there is no threshold below which no
harmful effect is observed.
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.
TLC method can detect aflatoxins.
PROCESS-INDUCED FOOD TOXINS:

Modern processing techniques:
Heat treatments (preservation)
 Flavour enhancing
 Texture or appearance enhancing
 Shelf-life

Changes in food
 Chemical reactions between food components
 Desirable and Undesirable (toxins)
 generate potentially harmful compounds.
 Examples: Partially hydrogenated oils, Sodium
nitrate/nitrite levels, MSG, Pesticides, artificial
sweeteners


It Involves:
naturally-occurring components in the food
 food additives, ingredients,
 food packaging materials that were intentionally used.


Examples of such Food process induced chemicals:









Acrylamide
Benzene
Chloropropanols
Ethyl carbamate
Furan
Heterocyclic aromatic hydrocarbons
Nitrosamines
Polycyclic aromatic hydrocarbons (PAH's)
Semicarbazide
MEASUREMENT OF TOXICITY
WHAT IS TOXICITY?


The toxicity of a substance is its capacity to cause injury to a living
system.
Toxicity represents the kind and extent of damage that can be done
by a chemical or how poisonous something is.
KINDS OF TOXICITY:

Acute toxicity:

Acute toxicity is used to describe effects which appear promptly, or
within 24 hours of exposure.

The acute toxicity of a pesticide is used as the basis for the warning
statements on the label.

Acute toxicity may be measured as acute oral toxicity, acute dermal
toxicity, and acute inhalation toxicity.

Chronic toxicity:

It is the delayed poisonous effect from exposure from a substance.

It is measured in experimental conditions after three months of either continuous
or occasional exposure.

The effects of both acute toxicity and chronic toxicity are dose-related; the greater
the dose, the greater the effect.
RISK = TOXICITY X EXPOSURE
The risk of harm from a toxicant exposure is equal to how poisonous
the toxicant is, multiplied by the amount and route of exposure to
the toxicant
MEASUREMENT OF ACUTE TOXICITY:

Lethal dose (LD50):


This is defined as the dose required to kill half the members of a specific
animal population when entering the animal’s body.
LD50 is stated in milligrams per kilogram (mg/kg): milligram of chemical per
kilogram of body weight
 The lower the LD50--the lower the lethal dose-the more toxic the
substance.
 The term LC50-Lethal Concentration is used to measure the toxicity of
gases. The LC50 is stated in milligram of chemical per liter (or cubic meter)
of air.
 Fixed
dose procedure:

In 1992, the fixed-dose procedure (FDP) was proposed as an alternative test to
LD50.

Fewer animals used, less pain and suffering.

Here the test substance is given at one of four fixed-dose levels (5, 50, 500 and
2000 milligrams per kilogram) to five male and five female rats.

When a dose produces clear signs of toxicity but no death is identified, the
chemical is then classified at that level.
Parts
per million:

To compare chemicals causing toxicity at very low levels.

Parts per million (ppm), parts per billion (ppb) and parts per
trillion (ppt) are the most commonly used terms.

They are measures of concentration – the amount of one
substance in a larger amount of another substance.

Scientists often use these measurements when measuring
a toxic chemical in a lake or toxins in the air such as
greenhouse gases.
MEASUREMENT OF CHRONIC TOXICITY:

Carcinogenic toxicity:
 Carcinogenesis bioassay:
 Utilizes high-dose studies on laboratory animals to look for even the
rare case of cancer for 24-30 months


It may not be the best scientific approach but is an effective way to
address to public concerns by generating carcinogenic risk values.
For carcinogenic toxicity, scientists try to find even the rare cases of
cancer.

Non-carcinogenic toxicity:

Lowest Observable Effect Level (LOEL)
 Looking for the smallest dose of the substance that cause a
detectable change.



For dose-response studies: administering small doses to substances
to several groups of test animals everyday over a lifetime.
Periodically observing animals and final autopsy to determine the
effect.
LOEL is measured in milligrams (mg) of substance per kilogram (kg)
of body weight, or in parts per million (ppm) of substance in food.
 Determining



Safe Levels:
To protect the public, scientists also determine the highest dose at
which no effects occur, known as No Observable Effect Level
(NOEL).
The NOEL is considered the "safe level" for that chemical in the
species studied.
The NOEL is not necessarily the "safe level" for humans,
because:
humans may be more/less sensitive to the substance than the animals
studied.
 humans have more genetic, health, age, and other variability's, which
may affect individual human reactions.

NOAL: NO OBSERVABLE ADVERSE EFFECT LEVEL
LOAEL: LOW OBSERVABLE ADVERSE EFFECT LEVEL
HUMAN SENSITIVITY & VARIABILITY:


The "safe level" calculation for humans assumes that humans are more
sensitive than animals, but humans are not more sensitive in all cases.
This variation is usually due to the different degrees and rates of
absorption, metabolism, and/or excretion of the substance by the different
species.
 Mathematical
models vary:

A mathematical model is a set of equations that mimic a real situation and
predict what will happen under different circumstances.

For toxicity assessments, models are made to apply the values obtained from the
animal studies to human conditions.

The choice of model strongly affects the outcome of the toxicity assessment.
 Non-Threshold

Non-Threshold Model:


vs. Threshold Models:
It is based on the assumption that even one molecule of a cancer-causing agent can lead to the
disease. This type of model is also referred to as a "one-hit" model.
Threshold Model:

It is based on the premise that repeated exposures to a chemical are needed before a threshold
of exposure is reached and cancer follows.
RISK ASSESSMENT:
The risk assessor estimates ‘real world’ risk by combining information on
toxicity and exposure.
•
•
A toxicity assessment provides information on how much of a chemical
causes what kind of harm.
Toxicity assessment provides only an estimate of the harm to humans.
TOXICOKINETICS & TOXICODYNAMICS


Toxicokinetics (Determines the no. molecules that can reach the
receptors)
 Uptake
 Transport
 Metabolism & transformation
 Sequestration
 Excretion
Toxicodynamics (Determines the no. of receptors that can
interact with toxicants)
 Binding
 Interaction
 Induction of toxic effects
IMPORTANT PRINCIPLES
- The effect which a drug produces is dependent on:
1.
2.
The dose
The concentration in the target organ
- The kinetics of a drug may differ from therapeutic dose to its toxic dose
- Toxicokinetics is important in predicting the plasma concentration of a drug
UPTAKE AND ELIMINATION
Uptake
K1
Biological
System
K2
Elimination
K1 > K2 : Accumulation & Toxic effect
A
C- max
Conc.
minimum toxic conc.
B
T-peak
Slowing of absorption (AB)
- prolonged Tp
- lower Cmax
Time
In instances when the absorption rate is slower than elimination rate,
the rate of washout of toxicant becomes rate-limited by absorption
rather than by elimination (i.e., a depot effect).
Absorption faster than elimination
Elimination faster than absorption
i.v. dose
i.v. dose
log
Conc.
non-i.v. dose
log
Conc.
non-i.v. dose
Time
Time
TOXICOKINETICS
1.
2.
3.
4.
5.
Uptake
Transport
Metabolism & Transformation
Sequestration
Excretion
ABSORPTION - UPTAKE ROUTES
1.
2.
3.
Ingestion (toxicity may be modified by enzymes,
pH and microbes)
Respiration (Air borne toxicants)
Body surface (Lipid soluble toxicants such as
carbon tetra chloride and organophosphate)
UPTAKE BARRIERS
1.
2.
3.
4.
5.
Cell membrane
Cell wall/cuticles/stomata
Epithelial cells of GI tract
Respiratory surface (lung, gill tracheae)
Body surface
UPTAKE OF TOXICANTS
1.
2.
3.
4.
Passive diffusion
Facilitated transport
Active transport
Pinocytosis
UPTAKE BY PASSIVE DIFFUSION
Uncharged molecules may diffuse along conc. gradient until
equilibrium is reached
 Not substrate specific
 Small molecules of < 0.4 nm (e.g. CO, N20, HCN) can move
through cell pores
 Lipophilic chemicals may diffuse through the lipid bilayer

UPTAKE BY PASSIVE DIFFUSION

First order rate process, depends on:
 Concentration gradient
 Surface area (aveoli = 25 x body surface)
 Thickness (fluid mosaic phospholipid bi-layer ca. 7 nm)
 Lipid solubility & ionization(dissolved before transport, polar
chemicals have limited diffusion rate)
 Molecular size (membrane pore size = 4-40 A, allowing MW of
100-70,000 to pass through)
UPTAKE BY FACILITATED TRANSPORT
 Carried
by trans-membrane carrier along concentration
gradient
 Energy independent
 May enhance transport up to 50,000 folds
 Example: Calmodulin for facilitated transport of Ca
UPTAKE BY ACTIVE TRANSPORT
Independent of or against conc. gradient
 Require energy
 Substrate –specific
 Rate limited by no. of carriers
 Example:
 P-glycoprotein pump for xenobiotics (e.g. OC)
 Ca-pump (Ca2+ -ATPase)

UPTAKE BY PINOCYTOSIS
 For
large molecules ( ca 1 um)
 Outside: Infolding of cell membrane
 Inside:
release of molecules
 Example:
 Airborne toxicants across alveoli cells
 Carrageenan accross intestine
TRANSPORT & DEPOSITION

Transport
Blood
 Lymph, haemolymph
 Water stream in xylem
 Cytoplamic strands in phloem


Deposition
Toxicant
Pb
Cd
OC, PCB
OP
Aflatoxin
Target organs
Bone, teeth, brain
Kidney, bone, gonad
Adipose tissue,milk
Nervous tissue
Liver
DISPOSITION
Ingestion
OF XENOBIOTICS
Inhalation
Intravenous
Intraperitoneal
Subcutaneous
Gastrointestinal
trac t
Intramusc ular
Lung
Dermal
Liver
Blood and lymph
Bile
ex tracellular
fluid
Kidney
Bladder
feces
Urine
Lung
Secretory
Structures
Expired Air
body
organs
soft
tis sue
Alveoli
Secretions
fat
bone


METABOLISM & TRANSFORMATION
Evolved to deal with metabolites and
naturally occurring toxicants
Principle of detoxification:
1.
2.
3.
Convert toxicants into more water soluble form
(more polar & hydrophilic)
Dissolve in aqueous/gas phases and eliminate
by excretion (urine/sweat) of exhalation
Sequestrate in inactive tissues (e.g bone, fat)
P450 SYSTEM
A
heme-containing cytochrome protein located in ER,
and is involved in electron transport.
 Highly conservative, occur in most plants & animals
 Two phases of transformation
 May increase or decrease toxicity of toxicants after
transformation (e.g turn Benzo[a]pyrene into
benzo[a]pyrene diol epoxide, and nitroamines into
methyl radicals)
 Inducible by toxicants
INDUCTION
OF
P450
Toxicant
Aryl Hydrocarbon
Receptor
Toxicant-Receptor
Complex
Bind at
Specific site
hours
Translocating
protein
m-RNA for CYP1A
PHASE I TRANSFORMATION
EXAMPLES OF PHASE I TRANSFORMATION

Hydrolysis
RCOO-R’ + H2O ---------> RCOO-H + R’-OH

Hydroxylation
NADP
NADP+
R-H --------------------------> R-OH + H2O
EXAMPLES OF PHASE I TRANSFORMATION

Epoxidation
O
R-CH==CH-R’ -----------> R---CH ----CH-R’
PHASE II TRANSFORMATION
IMPORTANT PHASE II ENZYMES
Glutathion
S-transferases (GST)
Epoxide Hydrolase (EH)
UDP-glucuronosyltransferase (UDP-GTS)
Sulfotransferase (ST).
EXAMPLES OF PHASE II TRANSFORMATION

Deamination
R-NH2 ---------------------------> R=O + NH3
EXAMPLES OF PHASE II TRANSFORMATION
 Dealkylation
R-CH2-CH3 ----------------------> R + CH3-CH2O
 Dehalogenation:
R-Cl
---------------------------------> R-H + Cl+
GLUTATHIONE-S-TRANSFERASE (GST)
O
R------R’ ----------------------> HO-R-SG
GST
R-Cl ------------------------------> R-SG + Cl
GST
SEQUESTRATION
Animals may store toxicants in inert tissues (e.g. bone, fat, hair, nail)
to reduce toxicity
 Plants may store toxicants in bark, leaves, vacuoles for shedding
later on
 Lipophilic toxicants (e.g. DDT, PCBs) may be stored in milk at high
conc and pass to the young
 Metallothionein (MT) or phytochelatin may be used to bind metals

EXCRETION
 Gas
(e.g. ammonia) and volatile (e.g. alcohol) toxicants
may be excreted from the gill or lung by simple diffusion
 Water soluble toxicants (molecular wt. < 70,000) may be
excreted through the kidney by active or passive transport
 Conjugates with high molecular wt. (>300) may be
excreted into bile through active transport
 Lipid soluble and non-ionised toxicants may be reabsorbed
(systematic toxicity)
THE TOXICOLOGICAL PROCESS
Molecular Targets Concept
Reaction Types;
Non Covalent Binding
Covalent Binding
Electron Transfer
Enzymatic Reaction
Outcomes;
Dysfunction
Destruction
Neoantigen Formation
CARCINOGENESIS
 The
process in which a normal cell
converted to a cancerous cell.
cell have no. of genes in it –
that decides its destination
 The
CARCINOGENESIS
 This
tumor formed due to carcinogenesis
 Tumor is of two types:
 Malignant
 Benign
Benign: remain in localized area
While malignant: invade near cells and spread in
whole body
CARCINOGENESIS
 Carcinogenesis
is a multistep process at both the phenotypic and
the genetic levels.
 It starts with a genetic damage:
 Environmental
Chemical (toxin substances)
Radiation (ionizing and non-ionizing)
Viral
 Inherited (egg and sperm- carrying mutated gene)
FACTORS CAUSING CANCER
 During
division the chances of cancer occurring is higher
than at rest
 These are following factors that cause cancer:
 primary determining factors;
 secondary determining factors (inheritance)
 favoring factors (sex, age, nutrition)
PRIMARY FACTORS
 This
is of our interest
 Physical and chemical factors
 Physical one involve ionizing and non-ionizing radiations
 : mineral substances, organic substances and mixed substances
(tobacco, food carcinogens, etc.).
 Chemical carcinogens act either directly, causing mutations, or
indirectly, reactivating repressed carcinogens.
TOXINS
 Toxin
not man made only but also present naturally in
food.
 Some of these are neutralized while processing such as
soaking, fermenting or cooking the food substance,
 others are poisonous in any form:
 Aflotoxin, hydrazine, lectin, goiterogen
EXAMPLES
Aflatoxin- fungal source- legumes
 Goitrogens- suppress the function of the thyroid gland by
interfering with iodine uptake
 Hydrazines: volatile carcinogens found in many raw mushrooms,
 Mice display a significant increase in the incidence of several types
of tumors after they are fed uncooked mushrooms.

CONTI
 Cooking
the mushrooms destroys a third of the hydrazine
compound
 Lectins:
 toxic protein compounds found in most foods, but in heavy
amounts in many seeds, grains and legumes
 damage the heart, kidneys and liver, lower blood clotting ability,
destroy the lining of the intestines, and inhibit cell division
 Cooking – neutralize and then gastric juice (some extend)
TUMOR ARE DIVIDED IN 3 GROUPS:
: which include approximately 90% of human
cancers, are malignancies of epithelial cells.
 Sarcomas: which are rare in humans, are solid tumors of
connective tissues, such as muscle, bone, cartilage, and
fibrous tissue
 Leukemia and lymphomas: cancer of precursor of blood cells
and lymph cells
 Carcinoma
AFLOTOXIN MODE OF ACTION
 Hepatocellular
carcinoma (HCC) -primary liver malignancy
worldwide
 . Its incidence is rising at alarming rates and has become a public
concern globally.
 Dietary exposure to aflatoxins -major HCC risk factors.
 Aflatoxin B1, which is a genotoxic hepatocarcinogen, which
presumptively causes cancer by inducing DNA adducts leading to
genetic changes in target liver cells.
MECHANISMS OF ACTION LEAD TUMOR
 . AFB1
is metabolized by cytochrome-P450 enzymes to the
reactive intermediate AFB1-8, 9 epoxide (AFBO) which binds to
liver cell DNA, resulting in DNA adducts

DNA adducts interact with the guanine bases of liver cell DNA
and cause a mutational effect in the P53 tumor suppressor gene at
the codon 249 hotspot in exon 7, which may lead to HCC.
PREVENTION AND CURE OF TOXICANTS
PURPOSE OF PREVENTION
Prevention is defined as the promotion of health by the individual
and the community.
 Prevention of toxic exposures is concerned with preventing
chemicals of synthetic or natural origin from reaching people in
amounts or at rates that exceed human tolerance to them.

Types of Prevention
A toxic exposure occurs when a susceptible individual or population
comes into contact with a chemical/toxin in a particular environment.
Primary
• Primary poisons
prevention activities
intervene before the event.
• Active strategies seek to
change attitudes, lifestyles
and behaviors of
individuals
• Passive strategies
automatically protect
people, by improving the
safety of products and the
environment where they
are used.
Secondary
• Secondary poisons
prevention is the action
taken after an exposure
has occurred, to prevent
the poisoning from
progressing to chronic
stage and to restore the
victim to his/her former
state of health.
• It includes the initial
steps to minimize the
effects of the toxic agent,
the diagnosis,
decontamination and first
aid treatment, and
specific antidote therapy.
Tertiary
• Tertiary poisons
prevention deals with the
diagnosis and treatment
of poisoning victims who
cannot be treated to full
recovery, to prevent death
or permanent disability.
MECHANISMS FOR MINIMIZING TOXIC EFFECTS
Every material can be poisonous under certain conditions.
Metabolic Degradation
 In mammals, the liver is the primary site of detoxification of both natural and
introduced poisons.
 Harmful products converted to harmless products
Excretion And Repair
 Effects of waste products and environmental toxins reduced by eliminating
via excretion.
 Tissues and organs often have mechanisms for damage repair by cellular
reproduction.
GUIDELINES TO PREVENT FOOD TOXICITY
Wash hands, utensils and food surfaces often.
 Keep raw foods separate from ready-to-eat foods. When shopping, preparing food
or storing food, keep raw meat, poultry, fish and shellfish away from other foods.
This prevents cross-contamination.
 Cook foods to a safe temperature.
 Refrigerate or freeze perishable foods promptly
 Defrost food safely.
 Throw it out when in doubt.

Food poisoning is especially serious and potentially life-threatening for young
children, pregnant women and their fetuses, older adults, and people with weakened
immune systems.
Following food items are harmful:
 Raw or rare meat and poultry
 Raw or undercooked fish or shellfish, including oysters, clams, mussels and scallops
 Raw sprouts, such as alfalfa, bean, clover and radish sprouts
 Unpasteurized juices and ciders
 Unpasteurized milk and milk products
 Soft cheeses, such as feta, Brie and Camembert; blue-veined cheese; and
unpasteurized chees

PURCHASE AND STORAGE
Keep packages of raw meat and poultry separate from other foods,
particularly foods to be eaten without further cooking.
 Buy products labeled “keep refrigerated” only if they are stored in
a refrigerated case.
 Buy dated products mentioning expiry date of product.
 Use an appliance thermometer to make sure refrigerator is
between 35 and 40 F and freezer is 0 F or below.

PREPARATION
When using slow cookers or smokers, start with fresh rather than frozen.
 Avoid interrupted cooking. Never partially cook products, to refrigerate and
finish later.
 If microwave cooking instructions on the product label are not appropriate for
your microwave, increase microwave time to reach a safe internal
temperature.
 Before tasting, boil all home-canned vegetables and meats 10 minutes plus
one minute per 1,000 feet.

DRUG THERAPIES
Oral rehydration therapy
 Antibiotics
 Antitoxin to neutralize toxins from C. botulinum (only given within
the first 72 hours)
 Amitriptyline to control the numbness and tingling from ciguatera
poisoning
 Apomorphine or ipecac syrup to cause vomiting and help rid the
body of toxins
 Atropine for mushroom poisoning
 Diphenhydramine and cimetidine for fish poisoning
 Mannitol for nerve-related symptoms of ciguatera poisoning

COMPLEMENTARY AND ALTERNATIVE THERAPIES
Complementary and alternative therapies are best used to
strengthen the body and aid in the prevention of food poisoning.
Nutrition
 Herbs
 Homeopathy

NUTRITION
Drink plenty of fluids (to prevent dehydration).
 Drink barley or rice water (to soothe inflamed stomach or
intestine).
 Taking probiotics, (Lactobacillus and acidophilus), can help
restore the balance of good bacteria in the intestine.
 Apple cider vinegar is a traditional remedy
 Cooking herbs, like thyme, rosemary, basil, coriander, sage, and
fennel have strong antimicrobial effects against food borne
pathogens.

NUTRITION
Specific Food poisoning
Alpha-lipoic acid
 Vitamin A
 Calcium phosphate

Supplements to avoid

Fish oil
HERBS









Milk thistle (Silybum marianum) is often used for liver disorders and is
widely used in Europe to treat Amanita mushroom poisoning.
Chinese and Japanese combination herbal remedies used for Listeria.
Asian ginseng (Panax ginseng)
Astragalus root (Astragalus membranaceus)
Chinese cinnamon bark (Cinnamomum aromaticum)
Ginger root (Zingiber officinale)
Licorice ( Glycyrrhiza glabra)
Peony root (Paeonia officinalis)
Skullcap (Scutellaria lateriflora)
HERBS


Herbs have antibacterial or antimicrobial properties that are
effective for treating food poisoning in humans.
Barberry (Berberis vulgaris) has also been used traditionally to
treat diarrhea from infectious causes such as E. coli and V. cholera.
HOMEOPATHY

Arsenicum album

Chamomilla

Podophyllum

Sulphur
HUMAN DISEASES CAUSED BY MOLDY FOODS
Disease
Molds Involved
Toxins Implicated
Aflatoxicosis
Aspergillus flavus, A
parasiticus
Aflatoxins
Ergotism
Claviceps purpurea, C. paspali,
C. fusiformis
Ergot Alkaloids
Alimentary toxic aleukia
Fusarium sporotrichiodes
T-2 toxin
Yellow rice
(cardiac beri beri)
Penicillium citreoviride
Luteoskrin, Islanditoxin
AFLATOXICOSES
Acute lethal toxicity
 Immune suppression
 Hemorrhagic anemia syndrome
 Hepatotoxicity
 Teratogenicity
 Carcinogenicity

EFFECTS OF AFLATOXINS ON IMMUNITY
Effects on cellular responses, Phagocytosis by macrophages reduced
 Delayed cutaneous hypersensitivity reduced
 Lymphoblastogenesis reduced (response to mitogens)
 Effects on humoral factors Immunoglobins (IgG and IgA)
concentrations in serum may be reduced
 Complement activity reduced

AFLATOXIN—A HUMAN CARCINOGEN
Incidence of Liver Cancer (HCC)
 589,000 deaths in 1999 (WHO)
 HCC is the third leading cause of cancer death worldwide
 >80% of HCC occurs in the developing world
 >400 million HBV carriers worldwide

GOITER TREATMENT
Observation: If goiter is small and doesn't cause problems, and thyroid is
functioning normally.
 Medications: In hypothyroidism, thyroid hormone replacement with
levothyroxine will resolve the symptoms of hypothyroidism as well as slow
the release of thyroid-stimulating hormone from pituitary gland, often
decreasing the size of the goiter. For inflammation of thyroid gland, your
doctor may suggest aspirin or a corticosteroid medication to treat the
inflammation.

GOITER
Surgery: Removing all or part of your thyroid gland (total or partial
thyroidectomy). Surgery is also the treatment for thyroid cancer
 Radioactive iodine: radioactive iodine is used to treat an overactive thyroid
gland. The radioactive iodine is taken orally and reaches thyroid gland
through bloodstream, destroying thyroid cells. The treatment results in
diminished size of the goiter, but eventually may also cause an underactive
thyroid gland.
