Clinical Toxicology

Phar 3132
 Chapter 1

Origin & Scope of

Toxicology
Outline

•Introduction to Toxicology

•History of Toxicology

•Different Areas of Toxicology

 I. Introduction to Toxicology

Toxicology: Derived from Greek word, toxikon and

logos •
the study of the adverse effects of chemical,
physical, or biological agents on living organisms
and the ecosystem, including the prevention and
amelioration of such adverse effects."
The science of poisons that studies toxic substances
with respect to their:
Sources , Properties , Mechanism of toxicity
Toxic effects, Detection , Clinical manifestations
Not everyone will respond to substances in
exactly the same way. 3
Introduction to Toxicology…..

 Chemical Sources: like drug, corrosives

 Plant sources: hashish, cocaine
 Animal sources: animal venoms( scorpion,
spider, Snake
 A toxicologist is trained to examine &
communicate the nature of those effects on
human, animal, & environmental health
Toxicological research examines the cellular,
biochemical, & molecular MOT as well as
functional effects such as:
• Neurobehavioral & immunological, &
assesses the probability of their occurrence
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 Cont……
 Toxicologists they are involved in the recognition,
identification, and quantification of hazards resulting
from occupational exposure to chemicals and the
public health aspects of chemicals in air, water, other
parts of the environment, foods, and drugs.
Molecular toxicologist

Clinical toxicologist

Environmental toxicologist
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 Toxicological terms and definitions

 Toxin- a poison of natural (biological) origin 

 Poisons :any substance that produces disease

conditions, tissue injury or interrupts natural life
processes when in contact with or absorbed into the
body.
 Toxic agent-Anything that can produce an adverse biological
effect.
It may be chemical, physical, or biological in form.
E.g chemical (such as cyanide), physical (such as radiation) and
biological (such as snake venom).
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Toxicosis describes the disease state
that results from exposure to poison
or poisoning and intoxication.

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Cont……
 Toxicity-any toxic (adverse) effect that a chemical
or physical agent might produce within a living
organism 
 Toxicant : A poison that is made by humans or
that is put into the environment by human
activities.
• chemical that can injure or kill humans,
animals, or plants; (poison)
Systemic toxin: Affects the entire body/many
organs.Not site specific
Organ toxin: Affects only specific tissues or organ
 Hazard - is the likelihood that injury will occur in a
given situation or setting: the conditions of use and
exposure are primary considerations
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 Cont…….
 Risk - is defined as the expected frequency of the
occurrence of an undesirable effect arising from
exposure to a chemical or physical agent
RISK= HAZARD + EXPOSURE
 The toxicity depends on a variety of factors: dose,
duration and route of exposure, shape and structure
of the chemical itself, and individual human factors.
 toxicity is a relative term applied in comparing one
chemical with another.
 A highly toxic substance causes damage to an organism if
administered in a very small amount. But a substance of low
toxicity will not produce an effect unless the amount is very
large.
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 II. History of Toxicology

A. Antiquity
Toxicology dates back to the earliest humans, who used
animal venom & plant extracts for hunting, warfare, &
assassination
The Ebers papyrus (circa 1500 B.C.) describes many
recognized poisons- hemlock, aconite, opium, lead,
copper, antimony, digitalis, belladonna alkaloids
Theophrastus (370–286 B.C.), a student of Aristotle, wrote
De Historia Plantarum
Socrates (470-399 B.C.) received poison as part of state
execution

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Antiquity…

 Demosthenes (385– 322 B.C.) and Cleopatra’s

(69–30 B.C.)
Voluntary took poison
 King Mithridates (134-63 B.C.) of Pontus
Poisoned many criminals in his experiments to
identify antidotes
 Epidemic Poisonings in Rome lasted from 4th -1st
century B.C
 Dioscorides (Greek physician) 60 A.D.
 Described many poisons, devised categorization system
(plant, animal, mineral)
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 B. Middle Ages

 Moses Ben Maimon (Maimonides 1135–1204 A.D.)

Wrote poisoning and their Antidotes
 Renaissance Italians brought poisoning to a zenith
Catherine de Medici
Catherine Deshayes ( “La Voisine” )

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C. Age of Enlightenment

 Paracelsus (1493-1541)
Led the change from the science of Hippocrates and
Galen to that of the 17th century giants
Main Contributions by Paracelsus:
• Described the concept that “the dose makes the
poison”
• Toxicity is related to chemical structure
• Described the main clinical manifestations of two
common poisoning: arsenic & mercury

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D. Modern Toxicology

 Exponential growth parallels the World War II

with greatly increased production of drugs,
pesticides, organic chemicals

 During this period, the use of “patent” medicines

was prevalent, and there were several incidents
of poisonings from these medicaments

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Categories of Toxic effects

 Toxic effects may be grouped into:

 Local and systemic effect
 Reversible and irreversible effect
 Immediate and delayed effect
 Morphological effect
 Functional effect , Biochemical effect

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 Principal aspect of Toxicology

The principal aspects of Toxicology:

1.Toxicometrics: It is the study of measurement of poisons.

2.Toxicodynamics: It deals with the biochemical and

physiological effects of xenobiotics and mechanisms of
their action.

3.Toxicokinetics: It deals with the absorption, distribution,

biotransformation and excretion of xenobiotics.

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III. Different Areas of Toxicology

 Toxicology is broadly divided into different

classes Depending on: 
A. Research methodology 
B. Socio-medical 
C. Organ/specific effects
I. Based on research methodology
 The professional activities of toxicologists
fall into 3 main categories:
Descriptive, mechanistic, & regulatory
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 I. Based on research
 methodology
Descriptive, mechanistic, & regulatory
 Although each has distinctive characteristics,
each contributes to the other, & all are vitally
important to chemical risk assessment
A. Mechanistic Toxicology:
 Concerned with identifying & understanding the cellular,
biochemical, & molecular MZMs by which chemicals
exert toxic effects on living organisms
 In risk assessment, mechanistic data may be very useful:
i. In demonstrating that an adverse outcome
observed in lab animals is directly relevant to
humans
ii.This is important for rational treatment –
Facilitation of search for safer drugs (e.g. 18
organophosphates - malathione
 Different Areas of Toxicology …

 Mechanistic Toxicology…
E.g., the relative toxic potential of
organophosphate insecticides in
mammalians & insects can be accurately
predicted on the basis of an understanding of:
• Common mechanisms (inhibition of AchE )&
• Differences in biotransformation for these
insecticides among the different species
 Malathione has low mammalian toxicity B/c mammals
have carboxylesterases, that readily hydrolyze the
carboxyester link, detoxifying the compound. While
Insects, by contrast, do not readily hydrolyze this ester,
and the result is its selective insecticidal action 19
Different Areas of Toxicology …

 Mechanistic Toxicology…
ii. In identifying adverse responses in experimental
animals that may not be relevant to humans
• E.g. , the propensity of the widely used artificial
sweetener saccharin to cause bladder cancer
in rats may not be relevant to humans at
normal dietary intake rates
• B/c bladder cancer is induced only under
conditions where saccharin is at such a high
conc in the urine that it forms a crystalline
precipitate
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Different Areas of Toxicology …

 Mechanistic Toxicology…

iii. In the design & production of safer alternative

chemicals & in rational therapy for chemical
poisoning & Tx of disease

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Different Areas of Toxicology …

B. Descriptive Toxicology:
Concerned directly with toxicity testing, which
provides information for safety evaluation &
regulatory requirements

The appropriate toxicity tests in cell culture

systems or experimental animals are designed
to yield info to evaluate risks posed to humans
& the environment from exposure to specific
chemicals

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 Different Areas of Toxicology …
C. Regulatory Toxicology:

Decide, on the basis of data provided by

descriptive & mechanistic toxicologists, whether a
drug or other chemical poses a sufficiently low
risk to be marketed for a stated purpose or
subsequent human or environmental exposure
resulting from its use.
 Predictive toxicology : studies about the potential
and actual risks of chemicals /drugs 
This is important for licensing a new drug/chemical
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for use
II. Based on specific socio-medical issues

 Occupational toxicology – It deals with

chemical found in the workplace

E.g. – Industrial workers may be exposed to these

agents during the synthesis, manufacturing or
packaging of substances
 Agricultural workers may be exposed to harmful
amounts of pesticides during the application in
the field
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Different Areas of Toxicology …

 In addition to the above categories, there are

other specialized areas of toxicology such as:
Forensic toxicology

Clinical toxicology

Environmental toxicology

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Different Areas of Toxicology …

a) Forensic toxicology:
A hybrid of analytic chemistry & fundamental
toxicological principles
Concerned primarily with the medico-legal
aspects of the harmful effects of chemicals on
humans & animals
Primarily to aid in establishing the cause of
death & determining its circumstances in a
postmortem investigation

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Different Areas of Toxicology …

b) Environmental Toxicology
Focuses on the impacts of chemical
pollutants in the environment on biological
organisms
Although toxicologists concerned with the
effects of environmental pollutants on human
health fit into this definition, it is most
commonly associated with studies on the
impacts of chemicals on nonhuman
organisms such as fish, birds, terrestrial
animals, and plants
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Different Areas of Toxicology …

 Clinical toxicology:

Designates an area of professional emphasis in the

realm of medical science that is concerned with
disease caused by or uniquely associated with
toxic substances
Efforts are directed at treating pts poisoned with
drugs or other chemicals & at the development of
new techniques to treat those intoxications

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III. Based on the organ/system effect

 Cardiovascular toxicology
 Renal toxicology
 Central nervous system toxicology –
 Gastrointestinal toxicology
 Respiratory toxicology

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Fig. Graphical representation of the interconnections b/n different
areas of toxicology
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31
 Scope and Importance of Toxicology
 Toxicology deals with the toxicity studies of chemicals used:
1.In medicine for diagnostic, preventive and therapeutic
purposes.
2.In food industry as direct and indirect additives.
3.In agriculture as pesticides, growth regulators, artificial
pollinators, and animal food additives.
4.In chemical industry as solvent, components, and
intermediates of plastics and many other types of chemicals.
5.Toxicology is concerned with the health, effects of metals (as
in mines and smelters), petroleum products, paper and pulp,
toxic plants and animal toxins.

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 Toxicology may be helpful in the development of:
i. Suitable and safer food additives,
ii. Suitable and safer pesticides,
iii.Suitable drugs against any specific disease.
2. The data on acute toxicity tests Provides an idea
of toxic, sub-lethal & lethal dose of a specific
toxicant for specific animal

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Cont……

3. helpful in the antidotal therapy.

4. helpful in the monitoring of environmental pollution.
5. helpful in monitoring of risk assessment.
6. An understanding of the mechanism of toxic action
also contributes to the basic knowledge of
pharmacology, physiology, biochemistry and cytology.
7. Analytical toxicology provides suitable procedures to
evaluate the presence or absence of different types of
substances and their levels in the environment. the
permissible limit of any toxicant in any segment of the
environment.

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