I.

Introduction to Toxicology
Larry Johnson
Partnership for Environmental Education
and Rural health (PEER)
Texas A & M University

Definition of Terms
Toxicology is 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.

Introduction
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.

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 (14931541) 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, 2000
from the World Wide Web: www.iet.msu.edu/toxconcepts/toxconcepts.htm.

History
Italian physician
Ramazzini (1713) published
De Morbis Artificum
(Diseases of Workers)
described "asthma" in bakers, miners, farmers, gilders, tinsmiths, glassworkers, tanners, millers, grain-sifters, stonecutters, ragmen, runners,
riders, porters, and professors.
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 are 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.

Occupational and
Environmental Toxicology
- Paracelsus - Miners 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

Definition: 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.

Threshold Effects for Dose

Response

Dose-Response
Relationships

Is there such a thing

as a safe dose??

Agent A
Agent B

NOEL
(No Observable Effect Level)

Dose

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:
1.Ingestion (water and food)
2.Absorption (through skin)
3. Injection (bite, puncture, or cut)
4. Inhalation (air)

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 the Body Prevent the

Actions of Xenobiotics:
1) Redistribution
2) Excretion (primarily water soluble compounds)
- kidney and liver

3) Metabolism the major mechanism for terminating

xenobiotic activity, and is frequently the single most
important determinant of the duration and intensity of
toxic responses to a xenobiotic.
- LIVER, kidney, lung, GI, and others
Note: 1) and 2) are highly dependent upon 3)

Xenobiotics at Work
TOXICOKINETICS

Xenobiotic

Excretion

General Scheme of Xenobiotic Metabolism

Lipophilic
(parent compound)

Metabolism
Phase I
(oxidative)
Bioactivation
Detoxification

Hydrophilic
(metabolite)
1) Decrease biological activity
2) Increase excretability

Metabolites
polarity
functionality

Phase II
(synthetic)

Detoxification

Metabolites
size
ionization
water solubility
Increase excretability

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?

Role of Toxicologists
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)

Role of Toxicologists
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.

Role of Toxicologists
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.

Your Role
Risk is a part of everyday life, and ones decisions as to the
acceptability of a particular risk is influenced by
knowledge and experience.
While we cant do much about the experience part, we
can try to increase the publics knowledge about the
risks and benefits of all things chemical.
You play a critical role in this effort, and we cant do it
without YOU.

The power of EDUCATION