BPHA4552 Introduction to

Toxicology
Objectives
 Define toxicology and other toxicological terms
 Explain historical developments in the field of toxicology.
 Describe different aspects of toxicological sciences.
 Identify some poisonous substances in your home.
 List the routes of exposure to toxicants.
 Identify the responsibilities of toxicologist.
 Toxicology
What is toxicology? The study of the effects of poisons.

Poisonous substances are produced by plants, animals, or bacteria.

Phytotoxins
Zootoxins
Bacteriotoxins

Toxicant - the specific poisonous chemical.

Xenobiotic - man-made substance and/or produced by but not normally

found in the body.
 Introduction
Toxicology is arguably the oldest scientific discipline, as the earliest
humans had to recognize which plants were safe to eat.

Most exposure of humans to chemicals is via naturally occurring

compounds consumed from food plants.
Humans are exposed to chemicals both inadvertently and deliberately.
You Know ?
92% of all poisonings happen at home.

The household products implicated in most

poisonings are: cleaning solutions, fuels,
medicines, and other materials such as glue
and cosmetics.

Certain animals secrete a xenobiotic poison called

venom, usually injected with a bite or a sting,
and others animals harbor infectious bacteria.

Some household plants are poisonous to humans

and animals.
Do you know that?
 2.1 million cases of human exposures reported in 2000
 92% of the exposures occurred at home
 14% occurred in a health care facility
 2% occurred at work
 Children > 3 years were involved in 40% of the cases
 52.7% occurred in children > 6 years
 Male predominance is found among poison exposures younger than
13 years
 Children > 6 comprised 2.2% of the fatalities
 59% of fatalities occur in the 20-49 year age group
Finally in your knowing…
 85.9% of poison exposure were unintentional
 suicide intent was present in 7.5% of the cases
 therapeutic errors comprised 7% of exposures
 920 fatalities reported
 94% of adolescent and 79% of adults were intentional
 Automatic capital offense to poison someone
 Most poisonings occur at home just before meal time
 Most poisonings enter the body orally - 76.2%
 More people die in the US from suicides than from homicides
Substances most frequently involved
in Human Exposures
 Analgesics - 10%
 Cleaning substances - 9.5%
 Cosmetics and personal care products - 9.4%
 Foreign bodies - 5.0%
 Plants - 4.9%
 Cough and cold preparations - 4.5%
 Bites and envenomation - 4.2%
Substances most frequently involved in
Pediatric poisonings
 Cosmetics and personal care products - 13.3%
 Cleaning substances - 10.5%
 Analgesics - 7.2%
 Foreign bodies - 6.8%
 Plants - 6.6%
 Topicals - 6.3%
 Cough and cold preparations - 5.3%
Substances most frequently
involved in Adult Exposures

 Analgesics - 13.3%
 Sedatives/hypnotics/antipsychotics - 9.8%
 Cleaning substances - 9.5%
 Antidepressants - 8%
 Bites/envenomations - 7.9%
 Alcohols - 5.4%
History

2700 B.C. - Chinese journals: plant and

fish poisons

1900-1200 B.C. - Egyptian documents that had directions for collection,

preparation, and administration of more than 800 medicinal and poisonous recipes.

800 B.C. - India - Hindu medicine includes

notes on poisons and antidotes.

50-100 A.D. - Greek physicians classified over

600 plant, animal, and mineral poisons.
 History
50- 400 A.D. - Romans used poisons for
executions and assassinations.

The philosopher, Socrates, was executed

using hemlock for teaching radical
ideas to youths.

Avicenna (A.D. 980-1036) Islamic authority on

poisons and antidotes.

1200 A.D. - Spanish rabbi Maimonides writes

first-aid book for poisonings,
Poisons and Their Antidotes
History

Swiss physician Paracelsus (1493-1541)

credited with being
“the father of modern toxicology.”

“All substances are poisons: there is none

which is not a poison. The right dose
differentiates a poison from a remedy.”
 The Dose Makes the Poison

An apparently nontoxic chemical

can be toxic at high doses.
(Too much of a good thing can
be bad).

Highly toxic chemicals can be life

saving when given in appropriate
doses. (Poisons are not harmful
at a sufficiently low dose).
 Lethal Doses
Approximate Lethal Doses of Common Chemicals
(Calculated for a 160 lb. human from data on rats)
Chemical Lethal Dose
Sugar (sucrose) 3 quarts
Alcohol (ethyl alcohol) 3 quarts
Salt (sodium chloride) 1 quart
Herbicide (2, 4-D) one half cup
Arsenic (arsenic acid) 1-2 teaspoons
Nicotine one half teaspoon
Food poison (botulism) microscopic
Source: Marczewski, A.E., and Kamrin, M. Toxicology for the citizen, Retrieved August 17, 2018
from the World Wide Web: www.iet.msu.edu/toxconcepts/toxconcepts.htm.
 History
Italian physician
Ramazzini (1713) published
“De Morbis Artificum”
(Diseases of Workers)

describing "asthma" in bakers, miners, farmers, gilders,

tinsmiths, glass-workers, tanners, millers, grain-sifters,
stonecutters, ragmen, runners, riders, porters, and
professors. Ramazzini outlined health hazards of the dusts,
fumes, or gases that such workers inhaled. The bakers and
horse riders described by Ramazzini would today probably
be diagnosed as suffering from allergen-induced asthma.
The lung diseases suffered by most of the other workers
would now be classified as "pneumoconiosis," a group of
dust-related chronic diseases.
 History

Spanish physician Orfila (1815) established

toxicology as
a distinct scientific discipline.
 History
20th Century

Paul Ehrlich –developed staining procedures to observe cell and

tissues and pioneered the understanding of how toxicants
influence living organisms.
 History
20th Century

Rachel Carson - alarmed public

about dangers of pesticides
in the environment.
Occupational and
Environmental Toxicology
Environmental toxicants (air
and water pollutants) are
substances harmful to the
environment and to humans.
Environmental toxicants are both natural and
man made.

Public perception that man-made ones are more serious than natural
ones - Reality: both
are serious.
5,000,000 yearly deaths worldwide due
to bacterial toxicants (Salmonella, E. coli)
Occupational and
Environmental Toxicology
Many examples of diseases associated with specific occupations were
recorded in antiquity, but they were not considered serious
because the health of the workers was not a societal concern.

- Paracelsus - Miner’s Disease (1533)

- Hill & Pott (1761 &1775)
- Radium dial painters, “aniline dye” workers (1900)
- Shoe salesmen (1950s)
- Industrial chemical workers (1940-present)
Occupational and
Environmental Toxicology
- Paracelsus - Miner’s Disease (1533) came from inhaling
metal vapors, foundation for the field of chemotherapy.

- Hill (1761) linked tobacco (snuff)

to cancer.

- Pott (1775) linked scrotal cancer

and soot (benzo(a)pyrene) in
chimney sweeps.
 Occupational and
Environmental Toxicology
- Radium dial painters,
“aniline dye” workers (1900)
painters licked their brushes
to pull it to a point.

- Shoe salesmen (1950s)

shoe-fitting fluoroscopes:
radiation of feet in shoes
of children and repeated
exposure for salesmen.
 Occupational and
Environmental Toxicology

- Industrial chemical workers

(1940-present)

Workers typically are exposed to

a greater number of carcinogens
for longer periods of time.
Occupations with high risk of cancer :
Health care workers, pharmaceutical and
laboratory workers, refinery workers, rubber
workers, furniture makers, and pesticide workers.
Modern Toxicology

1961 - Society of Toxicology

1970s - EPA, FDA, and NIOSH

 Toxicology Terms

Toxicity - The adverse effects

that a chemical
may produce.

Dose - The amount of a

chemical that gains
access to the body.
 Toxicology Terms

Exposure – Contact providing

opportunity of
obtaining a
poisonous dose.

Hazard – The likelihood that the

toxicity will be
expressed.
Terms…….
 Toxicology - the study of poisons.
 “Toxicology is the study of the adverse physicochemical effects of
chemical, physical or biological agents on living organisms and the
ecosystem, including the prevention and amelioration of such
adverse effects.” - American Society of
Toxicologists
 Toxicologist - one who studies poisons
 Hazard - likelihood an event will occur based on how the product is
packaged, formulated, or its accessibility
 Risk - the probability that an event will occur based on patient
vulnerability
 Toxic substance - poisons
 Poison - any chemical substance which can cause harm
 Drug overdose - taking a harmful amount of a drug
Terms……
 Antidotes: from the Greek anti - against and didonai - to give
 the remedy for counteracting a poison
 3 types:
 chemical - reacts chemically with the poison to form a harmless compound, ie.
chelators and heavy metals
 mechanical - prevents absorption, ie. activated charcoal
 physiologic - counteracts the effects of the poison by producing opposite
physiologic effects, ie. atropine and organophosphate poisoning
 Universal antidote - 2 parts activated charcoal, 1 part magnesium oxide and 1
part tannic acid
Fundamental Rules of
Toxicology

Exposure must first occur for the chemical to present a risk.

The magnitude of risk is proportional to both the potency of the chemical

and the extent of exposure.

“The dose makes the poison” (amount of chemical at the target site
determines toxicity).
Exposure Concepts

Different toxic responses may arise from

different:

 Routes of exposure.

 Frequencies of exposure.

 Duration of exposure (acute vs.

chronic).
Routes of Environmental
Exposure

Ingestion (water and food)

Absorption (through skin)
Injection (bite, puncture, or cut)
Inhalation (air)
 Chemicals, Chemicals Everywhere

Everything in the environment is made of chemicals. Both naturally

occurring and synthetic substances are chemical in nature.

People are exposed to chemicals by eating or swallowing them, breathing

them, or absorbing them through the skin or mucosa.
People can protect themselves by blocking these routes of
exposure.
Duration & Frequency of Exposure

Duration and frequency are also important components of

exposure and contribute to dose.

Acute exposure - less than 24 hours; usually entails a single

exposure

Repeated exposures are classified as:

Subacute - repeated for up to 30 days
Subchronic - repeated for 30-90 days
Chronic -repeated for over 90 days
Exposure Concepts
Exposure to chemicals may come from many sources:

– Environmental
– Occupational
– Therapeutic
– Dietary
– Accidental
– Deliberate
 Individual Responses Can Be Different

The variety of responses among organisms that get the same dose of
chemical is due to individual susceptibility.
Dose and individual susceptibility play roles in all situations involving
chemicals, including those making medicine and caffeine.
 Introduction to Xenobiotics
*Recall: Foreign chemicals are
synthesized within the body are termed
xenobiotics (Gr.Xenos meaning “strange”)*

 Xenobiotics may be naturally

occurring chemicals produced by
plants, microorganisms, or animals
(including humans).

 Xenobiotics may also be synthetic chemicals produced by humans.

Poisons are xenobiotics, but not all xenobiotics are poisonous.

 How Xenobiotics Cause Toxicity

Some xenobiotics cause toxicity by disrupting normal cell functions:

 Bind and damage proteins (structural, enzymes)

 Bind and damage DNA (mutations)

 Bind and damage lipids

 React in the cell with oxygen to form

“free radicals” which damage lipid, protein,
and DNA
Types of Toxic Effects

Death - arsenic, cyanide

Organ Damage - ozone, lead

Mutagenesis - UV light

Carcinogenesis - benzene, asbestos

Teratogenesis - thalidomide
Target Organ Toxicity

Central Nervous System – lead

Immune System - isocyanates
Liver - ethanol, acetaminophen
Respiratory Tract - tobacco smoke,
asbestos, ozone
Eye - UV light (sunlight)
Kidney - metals
Skin - UV light, gold, nickel
Reproductive System –
dibromochloropropane
Mechanistic Toxicology

How do chemicals cause their toxic effects?

What Do Toxicologists Do?
Most toxicologists work to develop a
mechanistic understanding of how chemicals
affect living systems:

 Develop safer chemical

products
 Develop safer drugs
 Determine risks for chemical
exposures
 Develop treatments for chemical

exposures
 Teach ( e.g. other toxicologists,

graduate students, and youth)

 What Do Toxicologists Do?
Mechanistic toxicologists study how a chemical
causes toxic effects by investigating its absorption,
distribution, and excretion. They often work in
academic settings or private industries and develop
antidotes.

Descriptive toxicologists evaluate the toxicity of

drugs, foods, and other products. They often perform
experiments in a pharmaceutical or academic setting.

Clinical toxicologists usually are physicians or

veterinarians interested in the prevention, diagnosis,
and treatment of poisoning cases. They have
specialized training in emergency medicine and
poison management.
What Do Toxicologists Do?
Forensic toxicologists study the
application of toxicology to the law. They

?
uses chemical analysis to determine the
cause and circumstances of death in a
postmortem investigation.

Environmental toxicologists study the

effects of pollutants on organisms,
populations, ecosystems, and the
biosphere.

Regulatory toxicologists use scientific

data to decide how to protect humans
and animals from excessive risk.
Government bureaus such as the FDA
and EPA employ this type of toxicologist.
Regulatory Toxicology

Use data from descriptive and mechanistic toxicology to

perform risk assessments.

Concerned with meeting requirements of regulatory

agencies.

Industry/government interactions.
Review
Toxicology is the science that studies the harmful effects of
overexposure to drugs, environmental contaminants, and
naturally occurring substances found in food, water, air, and
soil.
 Main objectives are to establish safe doses and determine
mechanisms of biologic action of chemical substances.

A career in toxicology involves evaluating the harmful effects

and mechanisms of action of chemicals in people, other
animals, and all other living things in the environment.
 This work may be carried out in government, private
industry and consulting firms, or universities and other
research settings.

Toxicologists routinely use many sophisticated tools to

determine how chemicals are harmful.
(e.g.) computer simulations, computer chips, molecular
biology, cultured cells, and genetically-engineered
laboratory animals .
What Is the Risk?
People can make some choices about chemical exposure;
however, some exposure is controlled at a level other than
an individual one. Collective groups of people, such as
communities and governments, seek to control chemical
exposure on a community or global level.
Animals in
Research
“Virtually every medical
achievement of the last
century has depended
directly or indirectly on
research in animals.”
U.S. Public Health
Service
Summary
Toxicology is a fascinating science that
makes biology and chemistry interesting
and relevant.

Understanding HOW (i.e. mechanism)

something produces a toxic effect can lead to new ways of
preventing or treating chemically-related diseases. Animal
use in research is essential for medical progress.

Many diseases are the result of an interaction between our

genetics (individual variability) and chemicals in our
environment.

Toxicology provides an interesting and exciting way to apply

science to important problems of social, environmental,
and public health significance.
 Toxicology or Environmental
Health Science
is a “hook” to interest you in science and
non-science curricula.
 Hook
The science of toxicology provides a fantastic pedagogical opportunity to do
true ‘interdisciplinary’ teaching, to make relevant many of the exciting
biological discoveries that occur everyday.

Whether it is exploring the wonders

of the biology of DNA and heredity,
or the more mundane aspects of
acid-base chemistry, or the ethical,
legal, and social implications of
genetic testing for common
diseases such as cancer or
Alzheimer's -
 Hook
or the global ecological implications of species extinction;
or social risks and benefits of genetically modified foods -
or diagnosing the cause of the Mad Hatter’s strange behavior in Lewis
Carol’s ‘Alice in Wonderland’ (mercury poisoning)-
or the fall of the Roman Empire (lead poisoning),

toxicology and environmental health

science provide an interesting
“hook” to make the subject matter
– what ever it may be –

interesting and relevant to you.

Your Role

NIEHS, SOT, and PEER feels the responsibility to help educate the next
generation of citizens to better understand the world around them, and
especially to understand how chemicals – man-made or natural – present
both risks and benefits to society.

Of course, everything we eat, drink, breathe, touch, or use is made of

chemicals, so the task is LARGE!

We hope to make the science of toxicology ‘less obscure’ to you and the
public.
Your Role

Risk is a part of everyday life, and one’s decisions as to the

‘acceptability’ of a particular risk is influenced by
knowledge and experience.

While we can’t do much about the ‘experience part’, we

can try to increase the public’s knowledge about the
risks and benefits of all things chemical.

You play a critical role in this effort, and we can’t do it

without YOU.
The power of EDUCATION