Posts
Toxicology is the
science of poisons, which are sometimes referred to as toxins or toxicants. The
former
Term applies to all natural poisons produced by organisms,
such as the botulinum toxin produced by the bacteria Clostridium botulinum. The
latter more generic term includes both natural and anthropogenic (human-made)
toxicants like dichlorodiphenyl trichloroethane (DDT), which is perhaps the
most commonly recognized toxicant.
Even though the botulinum toxin is extremely toxic to
humans, and DDT is relatively toxic to insects, it is important to recognize
that virtually any element or compound will become toxic at some concentration.
For example, iron, which is an essential component of hemoglobin, can cause
vomiting, liver damage, and even death if it is ingested in excess. This
concept of toxicity was recognized five centuries ago by the Swiss alchemist
and physician Paracelsus (1493–1541), who stated that, "The right dose differentiates
a poison from a remedy." How much of the toxicant an organism receives
depends on both the exposure and dose. Exposure is a measure of the amount of a
toxicant that comes into contact with the organism through air, water, soil,
and/or food. Dose is a measure of the amount of toxicant that comes into
contact with the target organ or tissue, within the organism, where it exerts a
toxic effect. The dose is largely determined by how effectively the toxicant is
absorbed, distributed, metabolized, and eliminated by the body.
As a consequence, basic toxicological studies include
measurements of the effects of increasing doses of a toxicant on an organism or
some component of that organism (e.g., tissue, cell, subcellular structure, or
compound). The measurements are commonly plotted as dose–response curves. A
dose–response curve typically ranges from relatively low concentrations that do
not elicit a toxic effect to higher concentrations that are increasingly toxic.
One of the great challenges to the science of toxicology is
the prediction and discovery of chronic, sublethal responses. For example, in
the 1920s, excessive exposure of workers to tetraethyl lead (the lead in leaded
gasoline) in several United States gasoline production facilities caused approximately
fifteen deaths, and over three hundred cases of psychosis. Despite this
discovery of the apparent hazard of lead in gasoline, and the concerns of many
at the time, rigorous scientific studies were required to demonstrate the
subtle, sublethal dangers of chronic lead exposure, including adverse
neurological effects in children, which eventually led to the ban of lead
additives in gasoline in the United States.
Characterizing Toxicity
One measure of response is acute toxicity, which is the amount
of a toxicant that will cause an adverse effect within a relatively short
period of time (e.g., from instantaneous to within a few days). Another measure
of response is chronic toxicity, which is the long-term response to a toxicant.
Although the same types of dose–response curves are used to measure the chronic
toxicity
of toxicants, those measurements are more difficult to
quantify because the responses are often less absolute and more complex. For
example, chronic benzene toxicity causes lung cancer, but it may be years
before that benzene-induced cancer appears, and many other factors may retard
the development of that cancer ( antagonistic effect), contribute to its
development ( synergistic effect), or independently cause lung cancer (e.g.,
smoking cigarettes).
Forms of toxicity can also be characterized by the type of
adverse response they create. Carcinogens cause cancer, either by the
initiation or promotion of an uncontrolled growth of cells. Mutagens cause
mutations by altering the DNA sequences of chromosomes. Teratogens cause
mutations in the DNA structure of developing fetuses that can result in
developmental abnormalities. The latter form of toxicity includes the infamous
teratogen thalidomide, which was prescribed as a sedative for pregnant women
before it was found to cause severe birth defects in their children.
Differences in Sensitivities
Resolving the adverse effects of a toxicant are further
complicated by the variations in those effects in different species. Some
species are more sensitive to certain toxicants than others, and the effects of
toxicants on different tissues often vary between species. Because such
variations occur between humans and rodents, in spite of the similarity (95%) in
their DNA, extrapolations of laboratory studies on the effects of toxicants on
rats and mice to human health must always take this into account. Moreover, the
toxic effects of a pollutant on the gall bladder of humans cannot be determined
in studies involving rats because rats do not have gall bladders.
There are also relatively large differences in the
sensitivities and effects of toxicants between individuals of the same species.
Fetuses, neonates , and infants are more sensitive to the neurotoxic effects of
lead than older individuals, because lead interferes with the development of
the central nervous system, which is formed during the first few years of life.
Finally, healthy individuals are generally less sensitive to pollutants than
individuals with weakened immune systems who are less capable of responding to
additional threats to their health.
Genetics also plays a major role in the sensitivities of
individuals. Although some differences have been observed in humans, the most
commonly recognized genetic differences in toxic responses have been observed
in other species. These include the acquired genetic resistance of some
mosquitoes to DDT and some bacteria to antibiotics. However, the development of
molecular techniques to genotype humans has now made it possible to identify
individual sensitivities to different toxicants.
Risk Assessment
Another important aspect of toxicology is risk assessment,
which is a characterization of the potential adverse effects resulting from
exposure to a toxicant. Risk is the probability of an adverse outcome. The
basic steps involved in risk assessment are the identification of the magnitude
of the hazard, which is the potential for harm of a toxicant, and the resultant
characterization of risk, which is the probability of realizing that harm. The
results of risk assessments are routinely used by regulators to establish
acceptable concentrations of toxicants in the environment.
Environmental Toxicology
Environmental toxicology is a relatively recent field that
examines the occurrence of, exposure to, and form of toxicants in the
environment, and the comparative effects of these toxicants on different
organisms. DDT, for example, is a pesticide that has been used to control
mosquitoes responsible for spreading malaria. Although this pesticide is
effective in combating the spread of malaria, DDT and its chemical products
have also been found to affect reproduction in birds by causing egg shell
thinning, and in other organisms (e.g., alligators) by altering their estrogen
balance. Consequently, studies of toxicology now extend well beyond
dose–response assays of toxicants on specific target organisms to analyses of
their impact on entire ecosystems.
In addition to anthropogenic toxicants like pesticides,
environmental toxicologists also study naturally occurring toxicants, such as
metals and metalloids. Selenium, for example, is a naturally occurring element
that is essential at low concentrations in the diet of many animals. Excessive
intake of selenium, however, can be toxic to organisms. In the 1980s scientists
working at Kesterson Slough in the San Joaquin Valley, California, observed a
large number of deformed and dying waterfowl. The slough was part of a water
project designed to receive and evaporate excess irrigation water and remove
pesticides from the highly productive agriculture regions in the San Joaquin
Valley. The observed effects on the waterfowl were eventually linked to an
excess of selenium in the water. The selenium accumulated in the slough because
the soils and runoff from the valley were naturally rich in selenium, and
because evaporation in the slough further increased its concentration in the
water. In this example, it was discovered that a rare, but naturally occurring
and essential element was unwittingly concentrated to toxic levels in the
environment by human activity.
