Applied Toxicology

for Y-III-Bpharm Students

By

Berhan Begashaw
berhan.uog1912@gmail.com
Course objectives;
At the end of the course, students will be able to
 Define common terms of toxicology
 Explain briefly the history of toxicology
 Identify the different areas of toxicology
 Describe the general mechanisms of toxicity
 Explain the PKs of d/t toxicants
 Describe the general principle of Rx
 Discuss the toxicology of selected drugs and house
hold chemicals with their management
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Learning materials
• Casaret and Doull’s Toxicology: The Basic Science of
Poisons. New York,NY:McGraw-Hill: 2008

• Fundamentals of Toxicology: 2012

• Clinical toxicology principles and Mechanisms; 2005

• Principles of toxicology testing: Frank A.Barile;2007

• Other pharmacology books

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I. Introduction to Toxicology

Chapter Outlines
o Definitions

o The history of toxicology

o Branches of Toxicology

o Scope and application of toxicology

o Poison centers

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 Definitions
WHAT IS TOXICOLOGY?
 Derived from two Greek words:
Toxikon /toxin/ toxicum → poison
logos → discourse/study/knowledge

 The deleterious effects of chemicals, physicals or

biological agents

Adverse effects
– Any change from an organism’s normal state
– The concentration of active compound at the target
site for a sufficient time
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 Toxicologist
 Trained to examine the nature of those effects
(their cellular, biochemical & molecular MoAs) &
assess the probability of their occurrence.

 Poison = Toxicant
• Inorganic and organic lifeless substances

• Any substance causes deleterious effects in the

metabolism of living organism even in small dose.

• Toxic substances that are produced by or are a by-

product of anthropogenic activities
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 Poisons

 “Synthetic” does not mean toxic or poisonous

“Natural” does not mean safe or even low risk

 “Dioxin”
Produced during the production and/or
combustion of certain chlorinated organic
chemicals.

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 Which group of chemicals do you consider
to be toxic?
OR
 Which chemicals do you consider safe?
◦ Paracelsus (1493–1541)
“ All substances are poisons; there is none
which is not a poison. The right dose
differentiates a poison and a remedy.”

◦ Emil Mrak
“There are no harmless substances, only
harmless ways of using substances.”
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 Toxin
◦ Poisonous/toxic substance produced by a living
organism

 Phytotoxins
 Zootoxins
 Bacteriotoxins
 Mycotoxins

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 Xenobiotic

 A chemical compound that is foreign to the body

or living organisms.

 Toxicosis = Poisoning = Intoxication

 Describes the disease state which results from

exposure to a poison.

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 Toxic symptom
◦ Any feeling or sign indicating the presence of a
poison in the system.

 Toxic effects
◦ The health effects that occur due to exposure to
a toxic substance.

 Toxicity

◦ The adverse effects that a chemical may produce.

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 Exposure
 The actual contact of the chemical
substance with the biological organism.
 ( Contact with a hazard.)
 Hazard
 Chemical substance, physical agent, or
biological agent that can harm the
health of people.
 Risk
• The likelihood that the toxicity will be
expressed.
• = Hazard X Exposure

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 Safety
◦ The measure or mathematical probability that a
specific exposure situation or dose will not produce a
toxic effect.
 Risk assessment
◦ The process by which the potential (or probability of)
adverse health effects of exposure are characterized.
◦ Steps
 Toxicity determination
 Toxicity evaluation
 Hazard assessment
 Risk estimation
 Risk evaluation
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 Brief History of Toxicology
 History
of toxicology = History of the
human race

 The early humans must have learnt to

discriminate between things that were
good to eat and those that were not.

 Naturalprogression hunting,
warfare, homicide

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 Brief History…
 Ebers Papyrus (~1500 B.C.)

 The oldest well preserved medical

document

 > 800 medicinal & poisonous recipes,

many contain recognized poisons
(opium, hemlock, lead, copper
and antimony)

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 Brief History…..
 Socrates (470-399 B.C.)
 He was found guilty of corrupting the minds of the
youth of Athens & sentenced to death by drinking
a mixture containing poison hemlock.
 Hippocrates (400 BC: early era)
 The 1st to introduce the primitive principles of
toxicology.
 People were well aware of toxic effects of a no of
substances [ snake venom, poisonous plants,
hemlock and toxic minerals (As, Pb, Cu, etc.)]
 Some of these were actually used globally for their
toxic effects to commit homicide and suicide.
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Brief History…..
 Cleopatra – Queen of Egypt (69-
30 B.C.)

 Experimented with strychnine and

other poisons on prisoners and poor.

 Committed suicide with Egyptian Asp

(Egyptian cobra sometimes used in
executions).

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Brief History….
 Dioscorides (40-90 A.D.)

 Greek physician & pharmacologist who

classified poisons for Nero.

 Wrote the Materia Medica (5 volumes)

documenting over 600 MPs he encountered
while traveling with the Roman military, as
well as earlier compilations of Roman and
Greek knowledge.
 This was a standard text for 16 centuries!

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 Brief History…

Paracelsus (1493- 1541)

 The father of toxicology
“All things are poisons and nothing is
without poison, only the dose permits
something not to be poisonous.”

 Age of Enlightenment
“ All substances are poisons; there are
none which is not a poison, the right dose
differentiates a poison from a remedy.”
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Brief History…..
 Catherine Medici (1519-1589)
◦ She often used poisoning as a political tool
during her reign.
◦ Experimented with poisons on the sick and
poor to develop more advanced poisons.

 Mathieu Orfila (1787-1853)

◦ Established a systematic correlation b/n the
chemical & biological properties of poisons.
◦ Demonstrated effects of poisons on specific
organs by analyzing autopsy materials for
poisons and their associated tissue damage.

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 Brief History …

 Oswald Schmiedeberg (1838– 1921)

Made many contributions to the

science of toxicology.

Training of ~120 students who later

populated the most important
laboratories of pharmacology and
toxicology throughout the world.

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Brief History…..
20th Century
 Chemical Warfare (1915)
◦ By the middle of the 1910's, chemicals had
been developed to be used by the military
as weapons.

◦ Agents such as Chlorine, Chloropicrin,

Phosgene and Mustard gas were all used in
chemical warfare.

◦ Humans & dogs were fitted with gas masks.

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 Brief History…..
20th Century…
 Gerhard Schrader (1903-1990)
 Accidentally developed the toxic nerve
agents Sarin, Tabun, Soman, & Cyclosarin
while attempting to develop new
insecticides.
 As a result, these highly toxic gases
were utilized during World War II by the
Nazi's.
 Sometimes called the "father of the
nerve agents".

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20th Century…

 Paul Hermann Müller ; DDT – 1939

 Recognized as insecticide, who was

awarded the 1948 Nobel Prize in
Physiology and Medicine.

 DDT was banned in late sixties and

early seventies.

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 Brief History….
20th Century…
 Rachel Carson
 Alarmed public about dangers of
pesticides in the environment.

 Human role in ecology and as well as

safety from pesticides were some of
the fields she worked in.

 Scientist leads crusade against the use

of DDT, a pesticide and persistent
organic pollutant.

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 Brief History….
One now finds toxicology graduate programs in
 Medical schools

 Schools of public health

 Schools of pharmacy
 Programs in environmental science &
engineering, as well as
 Undergraduate programs at several
institutions.

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Different Areas
of
Toxicology

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 Clinical toxicology
Toxicologists are usually interested in
the Px, Dx & Rx of poisoning cases.

Deals with emergencies [ overdose,

poisonings & attempted suicides].

 Experimental toxicology

Toxicologists study the harmful effects

of chemical substances on living animals
(MoA, disposition, analytical procedures)

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 Environmental toxicology
Study the effects of pollutants on organisms,
populations, ecosystems, and the biosphere.
 Economic Toxicology
• Food toxicology
Deal with the possible deleterious effects of
chemicals in food for human consumption
(residue level).
• Drug Toxicology
 Occupational toxicology
Deals with chemicals found in the work place.
- Eg: pesticides, fertilizers,…
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 Forensic toxicology
Study the application of toxicology to the law.
-They use chemical analysis to determine the
cause & circumstances of death in a
postmortem investigation.

 Other special areas: Industrial toxicology,

Regulatory toxicology

Regulatory toxicologists use scientific data to

decide how to protect humans & animals from
excessive risk.

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 Analytical toxicology

Is the detection, identification, measurement of

drugs and other foreign compounds (Xenobiotic)
in biological and related specimens.

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 Causes of poisoning
o Suicide
Common among youth
o Homicide
Common among illiterates
o Accident
Common among children
o Therapy
Both outpatients and inpatients
o Occupation
Common among factory workers, lab
technicians, mining workers, etc.

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Scope and Application of Toxicology

 The contributions and activities of toxicologists are a

diverse and a wide spread
a) Contribute to physiology and pharmacology
b) Also participate in the development of standards
and regulations
c) Clinical toxicologists develop antidotes and
treatment regimes to ameliorate poisonings and
xenobiotic injury
d) Etc….

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 Poison centre
 The American Association of Poison Control Centers
defines
oPoison center, as an organization that serves a
designated geographic region & provides the
following services:
a) Poison information
b) Telephone management advice and
consultation about toxic exposures
c) Hazards surveillance to achieve hazard
elimination
d) Professional and public education in
poisoning Px, Dx, Rx.
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Thank U !!!

Q and Comment

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