Poisons and

Toxicology
 A POISON (TOXICANT) IS A SUBSTANCE
THAT IS HARMFUL TO LIVING ORGANISMS
BECAUSE OF ITS DETRIMENTAL EFFECTS ON
TISSUES, ORGANS, OR BIOLOGICAL
PROCESSES.
 TOXICOLOGY IS THE SCIENCE OF POISONS.
 A TOXICOLOGIST DEALS WITH TOXIC
SUBSTANCES, THEIR EFFECTS, AND THE
PROBABILITIES OF THESE EFFECTS.
A SUBSTANCE IS POISONOUS DEPENDS ON
THE TYPE OF ORGANISM EXPOSED, THE
AMOUNT OF THE SUBSTANCE, AND THE
ROUTE OF EXPOSURE.

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 Toxic substances may be classified according
to several criteria:
Chemically, such as heavy metals or polycyclic aromatic hydrocarbons,
some of which may cause cancer
Physical form, such as dusts, vapors, or lipid-soluble liquids
Source, such as plant toxins, combustion by-products, or hazardous
wastes produced by the petrochemical industry
Use, such as pesticides, pharmaceuticals, or solvents
Target organs or tissue, such as neurotoxins that harm nerve tissue
Biochemical effects, such as binding to and inhibiting enzymes or
converting oxygen-carrying hemoglobin in blood to useless
methemoglobin
Effects on organisms, such as carcinogenicity or inhibition of the
immune system

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 Toxic substances come in a variety of forms

from a number of different sources:

Toxins: come from natural sources
Toxicants: produced by human activities

Classification of factors that influence toxicity :

the toxic substance and its matrix
circumstances of exposure
the subject and its environment

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EXPOSURE TO TOXIC SUBSTANCES

The major routes of accidental or intentional exposure to

toxicants by humans and other animals are:
the skin (percutaneous route)
the lungs (inhalation, respiration, pulmonary route)
the mouth (oral route)
minor means of exposure are the rectal, vaginal, and
parenteral routes (intravenous or intramuscular, a
common means for the administration of drugs or toxic
substances in test subjects).

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How Tocicant enter the body

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Major sites of exposure, metabolism, and storage, and
routes of distribution and elimination of toxic substances in
the body.

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Absorption of a toxic substance
through the skin

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Representation of enterohepatic
circulation

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Pathways of toxicants in the
respiratory system

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DOSE–RESPONSE RELATIONSHIPS

Dose : the amount, usually per unit body mass,of a

toxicant to which an organism is exposed.
Response: the effect on an organism resulting from
exposure to a toxicant.

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Dose-response relationship is
based on :

The response is proportional to the concentration

at the target site
The concentration at the target site is related to
the dose
The response is causally related to the compound
administered

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RECEPTORS AND TOXIC
SUBSTANCES

almost always proteinaceous materials,

normally enzymes.
nonenzyme receptors include opiate (nerve)
receptors, gonads, or the uterus.

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Example of a toxicant acting on a receptor to
cause an adverse effect. When
acetylcholinesterase is bound by a xenobiotic
substance, the enzyme does not act to stop
nerve impulse. This can result in paralysis of
the respiratory system and death

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Disposition of toxic
compounds

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There are 4 phases are interrelated
:
Absoption
Distribution
Metabolism
Excretion

Absorption Distribution Metabolism

Excretion

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The dynamic phase is divided as
follows:

the toxicant reacts with a receptor or target organ in the primary reaction step
there is a biochemical response
and physiological or behavioral manifestations of the effect of the toxicant
occur.

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 Different major
steps in the
overall process
leading to a
toxic response

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Absorption of toxic
compounds
It must come into contact with a biological system
cell membranes
Structures of membranes ????
function and characteristics
Substances are able to pass through cell membranes,
depending on :
◦ Size
◦ Lipid solubility
◦ Similarity to endogenous molecules
◦ Polarity / charge

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 Transport systems :
Filtration through pores
◦ small molecules may pass through membrane pores
◦ occur down concentration gradient
◦ eg : ethanol, urea
Passive diffusion through the membrane phospholipid
◦ concentration gradient
◦ lipid soluble and non-ionized compound
Active transport
◦ require specific membrane carrier and energy
◦ inhibited by metabolic poisons
◦ saturated at high substrate concentration
◦ specific for endogenous and nutrient substances, eg : fluorouracil

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 Transport systems (continued)
Facilitated diffusion
◦ require specific membrane carrier, but no energy
◦ a concentration gradient
◦ saturated by high substrate concentration
◦ transport of glucose from the cells of the intestine into
bloodstream
Phago/pinocytosis
◦ Invagination of the membrane to enclose a particle or
droplet
◦ Insoluble substances eg : uranium and asbestos are absorbed
into the lungs

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 Sites of absorption :

Skin, gases, solvents and substances in solution, eg :

insecticide
Lungs, gases (carbon monoxide, sulphur dioxide,
nitrogen oxides), vapours from solvents (methylene
chloride), aerosols or particulate matter (asbestos,
fibre glass, pollen)
Gastrointestinal tract, drug, food

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Distribution of toxic
compounds
In the bloodstream the compound will distribute
around the body and be diluted by the blood
It distribute into the tissue depending on its physico-
chemical properties
Distribution into particular tissue involves crossing
biological membranes

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 Excretion of toxic
compounds
Urinary excretion, small and water soluble molecules
Biliary excretion, large polar substances
Excretion via the lungs, volatile compounds and
gaseous metabolites
Other route of excretion, milk, sweat, tears, semen

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 Urinary
occurs via the proximal tuble of the kidney
-kidney is most important; more compounds are
eliminated through the kidney than any other route
-liver transforms compounds into soluble products and
then metabolites are transported to the kidneys

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Fecal excretion
occurs as the result of two processes: excretion in the bile
which then enters the intestines, or direct excretion from
the GI tract
-compounds excreted through the digestive tract include
those contained in: non absorbed food, billiary excretion,
intestinal excretion, intestinal wall and gut flora

-billiary route is an important mechanism for the fecal

excretion of poisons and is even more important for the
excretion of their metabolites
-generally involves active secretion rather than passive
diffusion

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 Lung excretion
-elimination of gaseous and volatile compounds
-elimination is proportional to vapor pressure
-no specialized transport system; occurs via simple diffusion
-blood gasses are excreted by passive diffusion from the blood into
the avioli following a concentration gradient; occurs when the
concentration of a toxicant dissolves in the capillary blood and is
greater than the concentration of the substance in the aviolar air
-gasses with a low solubility in blood are more rapidly eliminated
than gasses with a high solubility
-volatile liquids dissolved in blood are also readily excreted via
respired air

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 Other Routes of
Excretion
primarily via mother’s milk, sweat, saliva, tears, and semen. Excretion into milk
can be important since toxicants can be passed with milk to the nursing
offspring.
In addition, toxic substances may be passed from cow’s milk to people.
Toxic substances are excreted into milk by simple diffusion. Both basic
substances and lipid-soluble compounds can be excreted into milk.
Basic substances can be concentrated in milk since milk is more acidic (pH ~
6.5) than blood plasma.
milk contains 3-4% lipids, lipid-soluble xenobiotics can diffuse along with fats
from plasma into the mammary gland and thus can be present in milk.
Substances that are chemically similar to calcium can also be excreted into milk
along with calcium. Examples of substances that can be excreted in milk are 
DDT, polybrominated biphenyls, and lead (which follows calcium kinetics).
Excretion of xenobiotics in all other body secretions or tissues (including the
saliva, sweat, tears, hair, and skin) are of only minor importance.

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endocrine disurption
-chemicals that interfere with the body' reproductive,
developmental, and behavioral systems
-affects may take years to appear in humans
-extreme lack of regulation by the government

-bisphenol A (BPA); linked to obesity, diabetes, breast and

prostate cancers, childhood anxiety and hyperactivity,
lowered sperm count, behavioral problems and other
issues, especially in animals exposed before birth

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