what is toxicology? what is the difference between poison and toxin? what is toxicity? what are different routes of toxicity? what is meant by dose-response curve?

1. Toxicology
1. Introduction
2. Poison and Toxin
3. Toxicity
4. Routes of Toxicity
5. Dose Response

2. Introduction
 Toxicology is derived from two greek words : ‘toxikon meaning poison
and ‘logos’ meaning study
 It is the study of adverse effect of chemicals or poisons on the
biological systems
 It includes
 Identification of poisons
 Their chemical properties
 Their biological effects
 Treatment of disease conditions that they may cause
 Toxic effects of poisons may be expressed in several ways
 Changes in growth, development, reproduction, pharmacokinetic responses,
pathology , biochemistry , physiology and behaviour.

3. Poison and Toxin
Poison is any solid, liquid or gas that can interfere with life
processes of cells of the organism and can exert
physiological or psychological disorders
Another term used for poison is toxicant – any agent
capable of producing deleterious response in a biological
system
Toxins originate from biological processes are classified as
biotoxins
Toxicosis describes the disease state that results from
exposure to poison or poisoning and intoxication.

4. Toxicologist
Studies the nature of adverse effect of
toxins at molecular, cellular, organ,
organism or even community level by
understanding how these agents affect the
system and how the system affects the
agents

5. Toxicity
Toxicity is the amount of a poison that under a specific set
of conditions causes toxic effects or results in detrimental
biological conditions
Expressed as milligrams (mg) of toxicant per kilogram (kg)
body weight that will produce a defined biological effect.
Dosage: total amount of toxicant per unit of body weight
Dose: total amount of toxicant received by a person

6. Routes of toxicity
Poisons or toxins can enter the body through 4 different
routes:
Ingestion:
The toxin is taken in the body by the oral route (eating or
drinking)
Toxins enters the blood through the walls of gastrointestinal
tract
Chemical properties of toxin will determine whether it will
absorbed in strongly acid stomach or the nearly neutral
intestine

7. Inhalation
Many toxins as gases or aerosols are
inhaled and enter the blood through lungs
Absorption and excretion of the toxic gases
and vapours depend primarily on their
aqueous solubilities

8. Dermal / topical
The toxins enters through the skin and moves into the
bloodstream
Epidermis largely limits absorption
Pesticides : Malathion and Parathion have caused
deaths in agricultural workers due to precutaneous
absorption
Chloro-vinylarsine dichloride: a mustard gas is
readily absorbed through intact skin

9. Parental Administration
The entry of the chemical is by injection:
Intravenous (iv)
Intraperitoneal (ip)
Intramuscular (im)
Most effective route of exposure is the
intravenous followed by iv, ip and im
Food toxicity occurs primarily due to oral route
e.g. consumption of contaminated food.

10. Dose Response
Major concept In toxicity is the relationship of dose and
response
According to Paracelsus: All substances are poisons;
there is none that is not a poison and the right dose
differentiates a poison and a remedy.
Any substance can provoke a dysfunction or injury at
some degree of exposure--- the dose makes the poison

11. Dose: The amount of substance entering into the
body. This is usually given as milligrams of the
chemical per kilogram of body weight (mg/kg) so
that dose can be compared across specimens.
The important parameters of toxicant to be
considered are:
Duration and frequency
Shape , size and solubility
How easily it will enters the body
How it will distribute within the body
The rate of its excretion from the body

12. Adverse effect or response
Adverse effect or response of toxin: any change from
an organism’s normal state that is irreversible at least for a
period of time
Producing an adverse effect depends on the concentration
of the active compound at the target site
Toxicity to an individual will vary due to individual genetic
variation, gender, age, nutritional status and health
conditions
Individual variation of the organism will affect absorption,
distribution, metabolism and excretion of the toxicant and
therefore, its overall effect.

13. Dose-response curve
“Dose” is the amount of drug to
administered to produce a certain degree of
response in a patient.
Dose-response relationship has two
components:
Dose-plasma concentration relationship
Plasma concentration-response relationship
Response- the change in the activity of cell
or tissue produced by the selected dose of the
drug is called the response.

14. The dose and response is closely related to
each other and this relationship is called
dose response relationship.
There is direct relationship between dose
intensity of response of the curve,
i.e. the intensity of response increases with
the increase in dose.
The typical curve showing the dose
response relationship is called dose
response curve (DRC).

15. As the dose of a toxicant increases, so does
the response.
For most toxicants, at very low amounts, there
will be no detectable effect of the chemical i.e.
no observed adverse effect level.
Larger amounts of chemical will cause
increasingly more severe biological
responses until a maximum level of damage
is reached.

16. Exposure
The physical properties of the toxin and its
concentration in the environment are important in
determining the extent of the exposure.
Toxic effects in biological systems are not
produced unless the agent and its metabolic
breakdown (biotransformation) products reach
appropriate target sites in the body at a specific
concentration and for a length of time sufficient to
cause toxicity.

17. The amount of toxin entering into body and its
frequency will determine the extent of toxicity.
 Acute toxicity will result within 24 hours if the dose
is high enough.
Repeated doses of the toxin over a period of 1 month
will result in Subacute toxicity.
When the exposure extends from 1 to 3 months
then it will result in Subchronic toxicity.
Chronic toxicity is caused by repeated doses of
the toxin over a period of 3 months or more.

19. Translocation
Biotransformation is the process by which
administered toxins or chemicals are modified by the
organism.
This can occur at any point during the compound’s
passage from absorption to excretion.
The key organs of biotransformation are:
Liver
Lungs
Kidneys
Intestine
Biotransformation may take place in two phases:
 Phase 1- enzymes make the toxicant more soluble
 Phase 2- enzymes link with a soluble agent (Conjugation)

20. The primary objective of metabolism is to
make the chemical agents more water
soluble and easier to excrete.
In some cases, biotransformation results in
the formation of reactive metabolites –
bioactivation.
Whether it is the parent compound or the
metabolite, it is the active compound that
does the damage.

21. Absorption & Distribution
The toxicant may have to pass many barriers to get to its
site of action.
Absorption is the ability of a chemical agent to enter the
blood which is in equilibrium with the other tissues and
target sites.
In intravenous route there is no limiting factor in
absorption and the toxin is 100 % bioavailable.
When toxin is inhaled, it must penetrate alveolar sacs of
lungs and then into capillary bed.
The intra-peritoneal toxin does not require absorption
through the GI tract,
Toxins through dermal and topical route need absorption
through the skin.

22. Distribution
Definition-The process in which chemical
agent translocates throughout the body is
termed as distribution.
The blood carries the agent to and from its
site of action, storage, depots, organs of
biotransformation and organs of elimination.
The rate of distribution is usually rapid and is
determined primarily by blood flow and the
chemical characteristics of the toxicant.

24. Storage
After absorption into the blood stream, the toxins
penetrate into various fluid compartments such as
plasma, interstitial fluid, transcellular fluid and cellular
fluids.
Generally equilibrium in most tissues takes place rapidly,
In bone and adipose tissues with rather poor blood
supply, relatively longer time is required to achieve
equilibrium in the toxins.
DDT i.e. is stored in fatty tissues, while lead and
fluoride are stored in the bones.
Some chemicals may accumulate in various areas as a
result of binding or due to their affinity for fat.

25. Excretion
Toxicants are eliminated from the body through several
routes:
a) Urinary excretion – water soluble products are filtered
out of the blood and excreted into the urine.
b) Exhalation – volatile compounds are exhaled through
breathing.
a) Biliary excretion – via faeces – compounds can be
extracted by the liver, biotransformed, and excreted into
the bile. The bile drains into the small intestine where the
eliminated compounds can be excreted into the faeces.
Faecal excretion also rids the body of non absorbed
compounds which pass through the GI tract.