Some Basic
Principles of Toxicology
Toxicology Enrichment Materials
This exercise is designed to
help you to understand some of the general principles that are
important to toxicologists in their quest to understand the biological
effects of chemicals. What follows is a description of several
terms that will help you to understand how to think about foreign
chemicals in natural systems. There are no reference materials
necessary for this exercise except the list of Toxicology terms
provided.
TOXICOLOGY
is a science that combines biology and chemistry
to study poisons and their effect on biological systems.
Name
several poisons:
Toxicologists talk about the TARGET of a toxicant. They are referring
to the particular macromolecule, cell, organ or biochemical process
that the toxicant disrupts. The way the toxicant is able to disrupt
that process is called the MECHANISM
OF ACTION of the toxicant. Not
all toxicants are lethal. They may also cause disease, tissue
damage, genetic alterations, cancer, etc.
For example, consider carbon
monoxide (CO). This poisonous gas is released from the combustion
of fossil fuels (car exhaust) and cigarette smoke. The CO molecule
competes with O2 for the same binding sites on hemoglobin. The
hemoglobin molecule cannot distinguish between the two molecules,
so CO gets transported in the blood instead of O2 causing oxygen
starvation of the tissues (in fact, carbon monoxide binds more
tightly than O2). At lower concentrations, this can cause changes
in heart rhythm, headache, weakness, nausea, dizziness and dim
vision. At greater concentrations, CO poisoning leads to unconsciousness,
coma, convulsions and possibly death. The effects of CO intoxication
can be reversible, except when severe oxygen deprivation causes
permanent neurologic damage. Thus, the target of carbon monoxide
poisoning is hemoglobin and its mechanism of action is competitive
binding to hemoglobin causing hypoxia (oxygen deprivation).
Describe, in general terms, the target and/or mechanism of
action for one of the poisons you named above:
Again consider the poisons you
named. What organism do they effect? Humans? Animals? One of the
primary ideas to appreciate in toxicology is that all living
things are potential victims of poisons. We most often think of
toxicant effects on humans and other animals, but all living things
can be affected adversely by chemicals that are not part of their
own metabolism.
Name
a drug or chemical product designed to kill.
Bacteria __________________________________
Fungi ___________________________________
Plants ___________________________________
Animals _________________________________
All living things are potential
targets of poisons. So, too, all chemicals are potential toxicants.
Paracelsus, a scientist from the Middle Ages, summed up this concept
by stating "all substances are poisons; there is none which is
not a poison. The right dose differentiates a poison from a remedy."
Restate
this famous quote in your own words:
The simplest and most common substances
can be toxic-even water.
How
do you suppose water could be toxic?
Name at least 3 substances which
you normally consider safe, and explain the circumstances by which
they could be harmful:
You should now be able to realize
the importance of those "circumstances" you described above. These
conditions are critical to the study of toxicology and are described
further below.
For an organism to have an
adverse effect from a chemical, it must first have been in contact
with it. This is called EXPOSURE.
Name
at least 5 xenobiotics to which you have been exposed in the last
24 hours:
Next you might think about how
you came into contact with those xenobiotics. The answer to this
question determines the ROUTE
of exposure. For example, you breathe in air pollutants, thus
the first contact points in your body would be your nasal passages,
airways, lungs, etc. (This would be the route of carbon monoxide
poisoning.)
Below are some other routes
of exposure for humans.
For each type of exposure,
list the organ(s) that will first have contact with potential
toxicants.
Touch ____________________________________
Ingestion __________________________________
Injection __________________________________
Toxicologists are also interested
in other characteristics of exposure.
Pretend
you are a detective at a "toxic" crime scene, and think of as
many questions as you can regarding the details of exposure:
One question you may have imagined
is something regarding the length of exposure, or duration. Toxicologists
define two types of exposure based on its duration. ACUTE
exposure is of brief duration. CHRONIC
exposure is a persistent exposure, over a long period of time.
Think about oil spills from
ocean tankers that transport the hazardous substance. You've probably
heard about the Exxon Valdez spill in Alaska because of its magnitude,
and the pristine area in which the spill occurred. This is an
example of acute exposure to oil by marine fish, mammals
and birds. Compare this to the chronic exposure that animals
that live along tanker routes or near oil terminals receive from
slow leaks and small spills that may not be nearly as great in
magnitude, but occur much more frequently.
Which
do you think is more significant? Why?
Duration is not the only significant
aspect of exposure. One of the most important questions that toxicologists
ask about exposure is - "how much?" This is called the DOSE.
This is important because for each chemical, a certain dose produces
certain biological effects in the individual organism. Any biological
effect caused by the exposure is called the RESPONSE.
Most of the time, the greater the dose, the greater the response
(as shown below), but this is not always true. Dose vs. response
curves can take many different shapes. The previous graph depicts
a linear relationship between dose and response.
Draw a dose vs. response
curve when a toxicant has no response at low doses, but requires
a high dose to observe a response. Draw another for a toxicant
which produces responses at low doses, but at some larger dose,
the magnitude of the response does not increase.
Earlier
in this exercise, you listed at least 5 xenobiotics to which you
were exposed in the last 24 hours. Did
you experience any adverse effects to any of these chemicals?
If so, describe these responses:
Regulatory toxicologists control
the toxicity testing that is done on foods and pharmaceutical
products. They must think about: What responses are considered
"adverse?" To what doses are the consumers most likely to be exposed?
Further, they must define the risk associated with each chemical,
and the level of risk that the public will accept.
For example, think about
an allergic reaction as an adverse effect of a xenobiotic. The
"toxicant" in this case might be a food or type of pollen. The
adverse reactions vary from individual to individual. They might
include skin rashes, asthma attacks, and even severe reactions
(anaphylaxis) that, if untreated, can lead to death. One food
that causes some allergies in people is peanuts.
Should
regulators ban peanuts and peanut-containing food from the public
market since it is a huge risk to some? Why
or why not?
That was an extreme example, but
regulators ask and answer these same types of questions when they
set standards for food contaminants and drugs. The analysis of
the nature and magnitude of risk is called RISK
ASSESSMENT.
You have now been introduced
to some of the basic principles of toxicology. Perhaps now the
next time you sit down to a meal, take medication or breathe in
some second-hand smoke, you will think of the toxicologist!
Describe
something you have learned or thought about in a new way as a
result of this exercise:
Teacher's Notes for Some
Basic Principles of Toxicology
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