Introduction to Toxicology. Larry Johnson Partnership for Environmental Education and Rural health (PEER) Texas A & M University. Toxicology. What is toxicology ? The study of the effects of poisons. Poisonous substances are produced by plants, animals, or bacteria. Phytotoxins
Partnership for Environmental Educationand Rural health (PEER)
Texas A & M University
What is toxicology? The study of the effects of poisons.
Poisonous substances are produced by plants, animals, or bacteria.
Toxicant - the specific poisonous chemical.
Xenobiotic - man-made substance and/or produced by but not normally found in the body.
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.
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 xenobioticpoison 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.
2700 B.C. - Chinese journals: plant and
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.
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
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.”
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).
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) microscopicLethal Doses
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.
HistoryItalian physicianRamazzini (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.
Spanish physician Orfila (1815) established toxicology as
a distinct scientific discipline.
Paul Ehrlich –developed staining procedures to observe cell and tissues and pioneered the understanding of how toxicants influence living organisms.
Rachel Carson - alarmed public about dangers of pesticides in the environment.
Environmental toxicants (air
and water pollutants) are
substances harmful to the
environment and to humans.
Environmental toxicants are both natural and
Public perception that man-made ones are more serious than natural ones - Reality: both
5,000,000 yearly deaths worldwide due
to bacterial toxicants (Salmonella, E. coli)
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)
- 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
“aniline dye” workers (1900)
painters licked their brushes
to pull it to a point.
radiation of feet in shoes of children and repeated
exposure for salesmen.
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.
1961 - Society of Toxicology
1970s - EPA, FDA, and NIOSH
Toxicity - The adverse effects
that a chemical
Dose - The amount of a
chemical that gains
access to the body.
Hazard – The likelihood that the
toxicity will be
Is there such a thing as a ‘safe’ dose??
“NOEL”(No Observable Effect Level)
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).
Different toxic responses may arise from different:
Ingestion (water and food)
Absorption (through skin)
Injection (bite, puncture, or cut)
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 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:
Exposure to chemicals may come from many sources:
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.
*Recall: Foreign chemicals are synthesized within the body are termed xenobiotics (Gr.Xenos meaning “strange”)*
Poisons are xenobiotics, but not all xenobiotics are poisonous.
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)
Lipophilic Hydrophilic(parent compound) (metabolite)
Phase I Phase II(oxidative) (synthetic)
Some xenobiotics cause toxicity by disrupting normal cell functions:
“free radicals” which damage lipid, protein,
Death - arsenic, cyanide
Organ Damage - ozone, lead
Mutagenesis - UV light
Carcinogenesis - benzene, asbestos
Teratogenesis - thalidomide
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 –
How do chemicals cause their toxic effects?
Most toxicologists work to develop a mechanistic understanding of how chemicals affect living systems:
graduate students, and youth)
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
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.
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.
Use data from descriptive and mechanistic toxicology to perform risk assessments.
Concerned with meeting requirements of
Toxicologyis the science that studies the harmful effects of overexposure to drugs, environmental contaminants, and naturally occurring substances found in food, water, air, and soil.
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.
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 .
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.
“Virtually every medical achievement of the last century has depended directly or indirectly on research in animals.”
U.S. Public Health Service
Toxicology is a fascinating science that
makes biology and chemistry interesting
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.
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 -
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 your
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 the public.
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.
Texas Rural Systemic Initiative
The Center for Environmental and Rural Health
Partnership for Environmental Education and Rural Health
College of Education, Texas A&M University
College of Veterinary Medicine at Texas A&M University