Introduction to Toxicology Larry Johnson Partnership for Environmental Education and Rural health (PEER) Texas A & M University Stolen by Mr. Chapman!

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.

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. Did You Know ?

2700 B.C. - Chinese journals: plant and fish poisons 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 A.D. - Greek physicians classified over 600 plant, animal, and mineral poisons. History

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 ) Islamic authority on poisons and antidotes A.D. - Spanish rabbi Maimonides writes first-aid book for poisonings, Poisons and Their Antidotes

Swiss physician Paracelsus ( ) 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.” History

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 Source: Marczewski, A.E., and Kamrin, M. Toxicology for the citizen, Retrieved August 17, 2000 from the World Wide Web: Approximate Lethal Doses of Common Chemicals (Calculated for a 160 lb. human from data on rats) ChemicalLethal 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 Nicotineone half teaspoon Food poison (botulism)microscopic

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

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. Toxicology Terms

Threshold Effects for Dose Is there such a thing as a ‘safe’ dose?? Agent A Agent B Dose Response “NOEL” (No Observable Effect Level) Dose-Response Relationships

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 days –Chronic -repeated for over 90 days

Exposure Concepts Exposure to chemicals may come from many sources: –Environmental –Occupational –Therapeutic –Dietary –Accidental –Deliberate

Children & Poisons

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.

Types of Toxic Effects Death - arsenic, cyanide Organ Damage - ozone, lead Mutagenesis - UV light Carcinogenesis - benzene, asbestos Teratogenesis - thalidomide

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? 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. ?

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.

is a “hook” to interest your students in science and nonscience curricula. Toxicology or Environmental Health Science