HAZARDOUS CHEMICAL MANAGEMENT

(BOSH1103)
LESSON 3
TOXICOLOGY
 Learning Objectives

At the end of the lesson, student will be able to:

1. Define toxicology.
2. Describe the lethal dose, lethal
concentration, effective dose and dose
response curve.
3. Explain the chemical effects to humans
4. Explain toxicokinetic processes.
 INTRODUCTION
• Toxicology is a field of science that helps us
understand the harmful effects that chemicals,
substances, or situations, can have on people,
animals, and the environment.
• Toxicology knowledge is important to predict what,
and how chemicals may cause harm to the human.
Subdivisions of Toxicology

Environmental toxicology

Economic toxicology

Forensic toxicology
 Environmental toxicology
Concerned primarily with the harmful effects of
chemicals that are encountered by humans because of
the presence of chemicals:
➢ in the atmosphere, or
➢ in the occupational setting, or
➢ through recreational activities, or
➢ by ingestion as food residues.
 Economic toxicology
Deals with the potentially harmful effects of chemicals
that are intentionally administered to living organisms
for the purpose of achieving a specific beneficial effect.
➢ Drugs developed for medicinal therapeutic purposes
in human or veterinary medicine,
➢ Chemicals developed for use as
pesticides or insecticides, or
➢ Substances designed as food
additives.
 Forensic toxicology
• Deals with the medical (diagnosis and treatment)
and legal aspects (cause-and-effect relationships) of
the harmful effects of chemicals on humans.

• Examples:
➢ Operation of a motor vehicle while under the
influence of alcohol
➢ Use of performance enhancing drugs in sporting
events
Terminology

Toxic

Toxicant

Toxin
 Terminology
• Toxic: This term relates to poisonous or deadly
effects on the body by inhalation, ingestion, or
absorption, or by direct contact with a chemical.

• Toxicant: A toxicant is any chemical that can injure or

kill humans, animals, or plants; a poison.

• Toxin: any poisonous substance of microbial,

vegetable, or synthetic chemical origin that reacts
with specific cellular components to kill cells, alter
growth or development, or kill the organism.
 What is toxicology?
Toxicology is a field of science that helps us understand
the harmful effects that chemicals, substances, or
situations, can have on people, animals, and the
environment.
 Toxicology
 A discipline that studies the ill-effect of
hazardous chemicals to humans
 Awareness due to the many chemicals in
the market
 Studies conducted using mice or rabbits to
determine permissible exposure limit to
humans
 Important in the proper selection of
personal protective equipment
 Who is a toxicologist?
A toxicologist is a scientist who has a strong
understanding of many scientific disciplines, such as
biology and chemistry, and typically works with
chemicals and other substances to determine if they
are toxic or harmful to humans and other living
organisms or the environment.
 Tobacco smoke
• Tobacco smoke is made up of thousands of
chemicals, including at least 70 known to cause
cancer.

• These cancer-causing chemicals are referred to

as carcinogens.
Some of the chemicals found in tobacco smoke
include:

• Nicotine
• Hydrogen cyanide
• Formaldehyde
• Lead
• Arsenic
• Ammonia
• Benzene
• Carbon monoxide (American Cancer Society)
 Chemicals Effect
 Acute effect
Instantaneous effect due to
chemical exposure of high
concentration at a short
period of time

 Chronic effect
Long term effect due to
chemical exposure at lower
concentration and/or
smaller quantity
Acute < 24hr
Subacute 1 mth
Subchronic 1- 3 mth
Chronic > 6 mth
 Chemicals Effect
 Localized effect
Effect is limited to the exposed body parts to
chemicals. For example, the local effect can be on
the skin, such as an acid burn, or in the digestive
tract when a hazardous agent is ingested.

 Systemic effect
Effect of chemical that spreads throughout the body.
For example, anaemia (a shortage of red blood cells)
which can be caused by a number of chemicals,
including: lead, beryllium, cadmium, mercury
compounds and benzene. Benzene can damage the
cells that form blood, leading to leukaemia.
 Routes of Entry

Injection

Direct contact Ingestion

Inhalation
 Routes of Entry

1. Inhalation – via the lungs

2. Direct contact – via the skin or eyes
3. Ingestion – via the gastrointestinal tract (GIT)
4. Injection – via direct puncture of the skin
“ All substances are POISON,
there is none that is NOT a
POISON”

Paracelsus (1493-1541)
Father of Toxicology
 Dose-response
• Not everyone will respond to substances in exactly the
same way.
• Below factors will influence whether a person will
develop a disease or not:
➢ duration of exposure
➢ an individual’s susceptibility to a substance
➢ a person’s age, all impact
➢ dose of the chemical or substance a person is exposed
to
• All substances have the potential to be toxic if given to
humans and other living organisms in certain conditions
and at certain doses or levels.
 Dose-response relationship
• Refers to relationship between the dose of a
chemical and the response it elicits.

• Response :
1. severity of effects
2. percentage population affected
 Dose-response relationship
(severity of effects)

response

Lethal response (LD)

Effective response (ED)

- safe reversible effect
(e.g. eye irritation)

Dose (D)
 Toxicity Indicators
 50% lethal concentration (LC50)
The concentration of chemicals in
the air that may result in the death
of 50% of the animal population
studied through inhalation for a short
period of time (ppm or mg/m3)/

Kepekatan bahan kimia dalam

udara yg menyebabkan kematian
kepada 50% populasi kajian. Kesan
daripada inhalasi bahan kimia
dalam sesuatu tempoh masa.
 50% Lethal dose (LD50)
Chemical dosage applied either
through ingestion, injection or applied
to the skin that result in the death of
50% of the animal population studied
(mg/kg)

 Dos bahan kimia yg diberi secara ingesi,

suntikan dan sentuhan melalui kulit yang
menyebabkan kematian 50% haiwan
kajian.
 Effective dose 50 (ED50)
• Efficacy can be seen as the maximum effect a
drug can cause at any given dose.
• ED50 can be seen either as the dose of a drug
at which 50% of the potential maximum effect
is produced, or it can alternatively be seen as
the dose at which the desired effect is
produced in 50% of the test subjects.
 100 Resistant
% individual
population
affected

50
Majority of population
responding

0 Dose
ED50
Sensitive
individual
DOSE RESPONSE RELATIONSHIP
(% population affected)
 Dose-response relationship.. Continue
(relative index of toxicity: LD50)
100
% population
affected

50

LD50 Dose

Use in chemical and pesticide toxicity rating

Dose-Response Relationship
Every chemicals have the potential of being
toxic, at a certain instance and level
“How much” concept

Death

Serious effect

Medium effect

Slight effect

No effect Dose
• NOAEL (No Observed Adverse Effect Level)
– is the highest data point at which there was NOT an
observed toxic or adverse effect.

• LOAEL (Low Observed Adverse Effect Level)

- is the lowest data point at which there was an observed toxic
or adverse effect
 Toxicokinetic

• Toxicokinetics is the study of the drug movement

around the body.
• Toxicokinetics study four processes (ADME):
1. Absorption
2. Distribution
3. Metabolism
4. Excretion
 Toxicokinetic
(Absorption)

• Ability of a chemical to enter the blood (blood is in

equilibrium with tissues)

• Routes of absorption

– Inhalation – via the lungs

– Direct contact – via the skin or eyes
– Ingestion – via the gastrointestinal tract (GIT)
– Injection – via direct puncture of the skin
 Toxicokinetic
(Distribution)

• Process in which chemical agent is transport via blood

and accumulation in organs and tissues

• Blood carries the agent to and from its site of action

 Toxicokinetic
(Metabolism)

• The process by which a substance absorbed into the

body changed into one or more chemically different
substances (metabolites)
• Two outcomes
- bioactivation: non-toxic is metabolized to toxic
metabolites.
- detoxification: toxic substance is metabolized to
non toxic metabolites
• Toxicity occur if detoxification pathway fails or
becomes saturated
 Toxicokinetic
(Metabolism)

Toxicant metabolite

e.g
Benzene phenol
Toluene hippuric acid
 Toxicokinetic
(Excretion)

 The process by which a substance that has been

absorbed and/or its metabolite(s) is eliminated
from the body.
 Common excretory route : urine, faeces, breath
(others: sweat, saliva, tears)
 Helps in biological monitoring
 Toxicokinetic
(Target organs)

• The organ or tissue where the adverse

effect occur or the site where a
substance is metabolized to toxic
metabolites.
• Some substances may have more than
one target organ
Acute vs Chronic Effects

Acute effects Chronic effects

 Asphyxiation  Carcinogenic
a condition that decreases the causes cancer
amount of oxygen in the body
 Mutagenic
 Corrosive
causes changes or mutation to
destroys bodily tissues human DNA

 Sensitizer  Teratogenic
ability to cause allergy causes newborns with
physical/mental disabilities
 Irritant
causes inflammation to the skin,
eyes and/or respiratory system
 Targeted Organs
Body Organs Chemicals
Lungs Halogen, hydrogen
sulfide
Liver Vinyl chloride,
aromatic,hydrocarbon
that includes chlorine
compound
Kidneys Mercury, calcium,
carbon tetrachloride
Blood Carbon monoxide,
hydrocarbons that
includes chlorine
compound
Neurologic Organophosphate,
carbon monoxide
Bones Flouride, selenium
Skin Arsenic, chromium
Exposure Limit

 Exposure limit expressed in ppm (parts

per million)
 Threshold limit values (TLV)
 TWA (Time Weighted Average)
 STEL (Short Time Exposure Limit)
 CL (Ceiling Limit)
 Immediately dangerous to life and
health (IDLH)
THANK YOU!