toxicology 30 min best

8/3/2019 Toxicology 30 Min Best

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Introduction to Toxicology

Larry Johnson

Partnership for Environmental Educationand Rural health (PEER)

Texas A & M University


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Toxicology

What is toxicology? The study of the effects of poisons.

Poisonous substances are produced by plants, animals, orbacteria.

Phytotoxins

ZootoxinsBacteriotoxins

Toxicant - the specific poisonous chemical.

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

normally found in the body.


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Introduction

Toxicology is arguably the oldest scientific discipline, as theearliest humans had to recognize which plants were safeto eat.

Most exposure of humans to chemicals is via naturallyoccurring compounds consumed from food plants.

Humans are exposed to chemicals both inadvertently and

deliberately.


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92% of all poisonings happen at home.

The household products implicated inmost poisonings are: cleaningsolutions, fuels, medicines, and othermaterials such as glue and cosmetics.

Certain animals secrete a xenobioticpoison called venom, usually injectedwith a bite or a sting, and others

animals harbor infectious bacteria.

Some household plants are poisonous tohumans and animals.

You Know ?


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2700 B.C. - Chinese journals: plant andfish poisons

1900-1200 B.C. - Egyptian documentsthat had directions for collection,preparation, and administration of

more than 800 medicinal and poisonous recipes.

800 B.C. - India - Hindu medicine includesnotes on poisons and antidotes.

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

600 plant, animal, and mineral poisons.

History


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History50- 400 A.D. - Romans used poisons for

executions and assassinations.

The philosopher, Socrates, was executedusing 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


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Swiss physician Paracelsus (1493-1541) credited with being

the father of modern toxicology.

All substances are poisons: there isnone which is not a poison. Theright dose differentiates a poisonfrom a remedy.

History


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The Dose Makes the Poison

An apparently nontoxic chemicalcan be toxic at high doses. (Toomuch of a good thing can be

bad).

Highly toxic chemicals can be lifesaving when given in appropriatedoses. (Poisons are not harmfulat a sufficiently low dose).


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Lethal Doses

Source: Marczewski, A.E., and Kamrin, M. Toxicology for the citizen, Retrieved August 17, 2000from the World Wide Web: www.iet.msu.edu/toxconcepts/toxconcepts.htm.

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


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describing "asthma" in bakers, miners, farmers, gilders,tinsmiths, glass-workers, tanners, millers, grain-sifters,stonecutters, ragmen, runners, riders, porters, andprofessors. Ramazzini outlined health hazards of the dusts,

fumes, or gases that such workers inhaled. The bakers andhorse riders described by Ramazzini would today probablybe diagnosed as suffering from allergen-induced asthma.The lung diseases suffered by most of the other workerswould now be classified as "pneumoconiosis," a group of

dust-related chronic diseases.

History

Italian physicianRamazzini (1713) publishedDe Morbis Artificum(Diseases of Workers)


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Spanish physician Orfila (1815) established

toxicology asa distinct scientific discipline.

History


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20th Century

Paul Ehrlichdeveloped staining procedures to observecell and tissues and pioneered the understanding of howtoxicants influence living organisms.

History


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20th Century

Rachel Carson - alarmed publicabout dangers of pesticides

in the environment.

History


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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 moreserious than natural ones - Reality: both

are serious.

5,000,000 yearly deaths worldwide due

to bacterial toxicants (Salmonella, E. coli)

Occupational andEnvironmental Toxicology


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Many examples of diseases associated with specificoccupations were recorded in antiquity, but they werenot considered serious because the health of the

workers was not a societal concern.

- Paracelsus - Miners Disease (1533)

- Hill & Pott (1761 &1775)

- Radium dial painters, aniline dye workers (1900)

- Shoe salesmen (1950s)

- Industrial chemical workers (1940-present)



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- Paracelsus - Miners Disease (1533) came frominhaling 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.



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- Radium dial painters,

aniline dye workers (1900)

painters licked their brushesto pull it to a point.

- Shoe salesmen (1950s)

shoe-fitting fluoroscopes:

radiation of feet in shoesof children and repeated

exposure for salesmen.



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- 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 andlaboratory workers, refinery workers, rubber

workers, furniture makers, and pesticide workers.



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Modern Toxicology

1961 - Society of Toxicology

1970s - EPA, FDA, and NIOSH


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Toxicity - The adverse effects

that a chemicalmay produce.

Dose - The amount of a

chemical that gains

access to the body.

Toxicology Terms


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ExposureContact providing

opportunity of

obtaining a

poisonous dose.

Hazard The likelihood that the

toxicity will be

expressed.

Toxicology Terms


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Threshold Effects for Dose

Is there such a thingas a safe dose??

Agent A

Agent B

Dose

Response

NOEL

(No Observable Effect Level)

Dose-ResponseRelationships


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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 ofthe chemical and the extent of exposure.

The dose makes the poison (amount of chemical at thetarget site determines toxicity).


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Exposure Concepts

Different toxic responses may arise fromdifferent:

Routes of exposure.

Frequencies of exposure.

Duration of exposure (acute vs. chronic).


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Routes of Environmental

Exposure

Ingestion (water and food)

Absorption (through skin)

Injection (bite, puncture, or cut)

Inhalation (air)


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Chemicals, Chemicals Everywhere

Everything in the environment is made of chemicals. Bothnaturally occurring and synthetic substances are chemical innature.

People are exposed to chemicals by

eating or swallowing them,breathingthem, or absorbing them through theskin or mucosa.

People can protect themselves byblocking these routes of exposure.


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Duration & Frequency of Exposure

Duration and frequency are also importantcomponents of exposure and contribute to dose.

Acute exposure - less than 24 hours; usually entails asingle 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


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Exposure Concepts

Exposure to chemicals may come from many sources:

Environmental

Occupational

Therapeutic Dietary

Accidental

Deliberate


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Children & Poisons


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Individual Responses Can BeDifferent

The variety of responses among organisms that get thesame dose of chemical is due to individual susceptibility.

Dose and individual susceptibility play roles in all situations

involving chemicals, including those making medicineand caffeine.


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*Recall: Foreign chemicals are

synthesized within the body aretermed xenobiotics (Gr.Xenosmeaning strange)*

Xenobiotics may be naturallyoccurring chemicals produced byplants, microorganisms, or animals(including humans).

Xenobiotics may also be synthetic chemicals produced byhumans.

Introduction to Xenobiotics

Poisons are xenobiotics, but not all xenobiotics are poisonous.


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How Does the Body Prevent the

Actions of Xenobiotics ?

1) Redistribution

2) Excretion (primarily water soluble compounds)

- kidney and liver

3) Metabolism the major mechanism for terminatingxenobiotic activity, and is frequently the single mostimportant 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)


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Xenobiotics at Work

Xenobiotic

Excretion

TOXICOKINETICS


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Metabolism 1) Decrease biological activity2) Increase excretability

General Scheme of Xenobiotic Metabolism

Lipophilic Hydrophilic(parent compound) (metabolite)

Phase I Phase II(oxidative) (synthetic)

Metabolites Metabolites

BioactivationDetoxification Detoxification

polarityfunctionality

sizeionization

water solubility

Increase excretability


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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


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Types of Toxic Effects

Death - arsenic, cyanide

Organ Damage - ozone, lead

Mutagenesis - UV light

Carcinogenesis - benzene, asbestos

Teratogenesis - thalidomide


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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, nickelReproductive System

dibromochloropropane


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Mechanistic Toxicology

How do chemicals cause their toxic effects?


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What Do Toxicologists Do?

Most toxicologists work to develop amechanistic understanding of howchemicals affect living systems:

Develop safer chemical

products

Develop safer drugs

Determine risks for chemicalexposures

Develop treatments for chemical

exposures

Teach ( e.g. other toxicologists,

graduate students, and youth)


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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 ofdrugs, foods, and other products. They often performexperiments in a pharmaceutical or academic setting.

Clinical toxicologists usually are physicians orveterinarians interested in the prevention, diagnosis,

and treatment of poisoning cases. They havespecialized training in emergency medicine andpoison management.


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What Do Toxicologists Do?

Forensic toxicologists study the

application of toxicology to the law. Theyuses chemical analysis to determine thecause and circumstances of death in apostmortem investigation.

Environmental toxicologists study theeffects of pollutants on organisms,populations, ecosystems, and thebiosphere.

Regulatory toxicologists use scientificdata to decide how to protect humans andanimals from excessive risk.Government bureaus such as the FDAand EPA employ this type of toxicologist.

?


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Regulatory Toxicology

Use data from descriptive and mechanistic toxicology toperform risk assessments.

Concerned with meeting requirements of

regulatory agencies.

Industry/government interactions.


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ReviewToxicology is the science that studies the harmful effects of

overexposure to drugs, environmental contaminants, andnaturally occurring substances found in food, water, air, andsoil.

Main objectives are to establish safe doses anddetermine mechanisms of biologic action of chemicalsubstances.

A career in toxicology involves evaluating the harmful effectsand mechanisms of action of chemicals in people, otheranimals, and all other living things in the environment.

This work may be carried out in government, privateindustry and consulting firms, or universities and otherresearch settings.

Toxicologists routinely use many sophisticated tools todetermine how chemicals are harmful.

(e.g.) computer simulations, computer chips, molecularbiology, cultured cells, and genetically-engineeredlaboratory animals .


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What Is the Risk?

People can make some choices about chemical exposure;however, some exposure is controlled at a level other thanan individual one. Collective groups of people, such ascommunitiesand governments, seek to control chemicalexposure on a community or global level.


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Animals in

ResearchVirtually every medicalachievement of the last

century has dependeddirectly or indirectly onresearch in animals.

U.S. Public Health

Service


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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 ofpreventing or treating chemically-related diseases. Animaluse in research is essential for medical progress.

Many diseases are the result of an interaction between our

genetics (individual variability) and chemicals in ourenvironment.

Toxicology provides an interesting and exciting way to applyscience to important problems of social, environmental,

and public health significance.


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is a hook

to interestyour students

in science and

nonsciencecurricula.

Toxicology or Environmental

Health Science


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The science of toxicology provides a fantastic pedagogicalopportunity to do true interdisciplinary teaching, to makerelevant many of the exciting biological discoveries thatoccur everyday.

Whether it is exploring the wondersof the biology of DNA and heredity,or the more mundane aspects ofacid-base chemistry, or the ethical,

legal, and social implications ofgenetic testing for commondiseases such as cancer orAlzheimer's -

Hook


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or the global ecological implications of species extinction;or social risks and benefits of genetically modified foods -

or diagnosing the cause of the Mad Hatters strange behavior inLewis Carols 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

students.

Hook


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Your Role

NIEHS, SOT, and PEER feels the responsibility to help educatethe next generation of citizens to better understand the world

around them, and especially to understand how chemicalsman-made or natural present both risks and benefits tosociety.

Of course, everything we eat, drink, breathe, touch, or use ismade of chemicals, so the task is LARGE!

We hope to make the science of toxicology less obscure to the

public.


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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.

Your Role

The power of EDUCATION


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The power of EDUCATION


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National Institute of

Environmental Health

Sciences

Partnership forEnvironmental

Education and Rural

Health

College of Education,

Texas A&M

University

Texas Rural Systemic

Initiative

The Center for

Environmental and

Rural Health

College of Veterinary

Medicine at Texas

A&M University

toxicology 30 min best

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