DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Environmental Toxicology:
Carcinogens and Heavy Metals
Michael C. Byrns
and Trevor M. Penning
Humans are exposed to chemicals from their environment
daily. Fortunately, mammals have evolved mechanisms
to protect themselves from toxic effects of many
exogenous chemicals, including the xenobiotic transport
and metabolic mechanisms described in Chapters 4-7.
While the human body is relatively well adapted to deal
with xenobiotics, there are situations in which such
environmental agents may cause significant toxicity.
The industrial revolution and the development of chemical
industries have increased human exposures to chemicals
that were previously infrequent or absent.
Occupational exposures to xenobiotics are of particular
concern because workers often will be exposed to specific
chemicals at concentrations that are orders of magnitude
higher than those to which the general population
is exposed. Increasing concern about environmental toxicants
has stimulated interest and research in environmental
toxicology, the study of how chemicals in our
environment adversely affect human health, and in occupational
toxicology, the study of how chemicals in the
workplace affect human health. Myriad authoritative
textbooks are available in these areas. This chapter does
not attempt a thorough coverage; rather, it sets forth a
few basic principles, briefly discusses carcinogens and
chemoprevention, and then focuses on the pharmacotherapy
of heavy metal intoxication.
ENVIRONMENTAL RISK ASSESSMENT
AND RISK MANAGEMENT
When assessing the risks of environmental exposures to
xenobiotics, many of the same principles discussed in
Chapter 4 for drug toxicity apply; there are, however,
significant differences. With environmental exposures,
one has to consider population exposures to low-dose
toxicants over long periods of time. Thus, one must give
more attention to the low end of the dose-response
curve, using experiments based on chronic exposures.
Particular attention is given to the potential for individuals
with higher susceptibility. Unlike drugs, which are
given to treat a specific disease and will have benefits
that outweigh the risks, environmental toxicants usually
are only harmful. In addition, exposures to environmental
toxicants usually are involuntary, there is uncertainty
about the severity of their effects, and people are much
less willing to accept their associated risks.
Two complimentary approaches are used to predict
the toxic effects of environmental exposures: epidemiology
and toxicology. Epidemiologists monitor
health effects in humans and use statistics to associate
those effects with exposure to an environmental stress,
such as a toxicant. Toxicologists perform laboratory
studies to try to understand the potential toxic mechanisms
of a chemical to predict whether it is likely to be
toxic to humans. Each of these approaches has strengths
and weaknesses, and information from both is integrated
into environmental risk assessment. Risk assessment
is used to develop management approaches, such
as laws and regulations, to limit exposures to environmental
toxicants to a level that is considered safe.
Epidemiological Approaches to Risk Assessment
Epidemiologists use multiple approaches to assess the risks of human
environmental exposures (Gordis, 2008). The disadvantage of these
approaches is the variability between people in their exposures and
genetics, which results in confounding effects. Epidemiologists cannot
control the environment or the genetics of the populations being
studied. For example, generally individuals are simultaneously
exposed to more than one environmental toxicant.
Because of the difficulties in assessing human exposures and
the long times required to clinically observe effects on health, epidemiologists
rely on biomarkers in risk assessment. There are three
different types of biomarkers: biomarkers of exposure, biomarkers of
toxicity, and biomarkers of susceptibility. Biomarkers of exposure
usually are measurements of toxicants or their metabolites in blood,
urine, or hair. Blood and urine concentrations measure recent exposures,
while hair levels measure exposure over a period of months.