PRINCIPLES OF TOXICOLOGY

514 EPIDEMIOLOGIC ISSUES IN OCCUPATIONAL AND ENVIRONMENTAL HEALTH
Observational studies can be divided into those that are predominantly descriptive (e.g., a description
of a possible disease–exposure association) and those that are analytical (e.g., an analysis of not
only the possible disease–exposure association, but of other relationships). Descriptive studies range
from a report of a series of unusual cases in the medical literature to surveillance of diseases in a
particular industrial population to reports of the health statistics of an entire country. With the exception
of ecologic studies (in which using grouped exposure data groups in one area are compared with groups
in another area, such as Japanese Hawaiians compared to native Japanese), descriptive studies only
include implicit comparisons. Descriptive studies are important for formulating possible hypotheses
concerning disease–exposure associations; they are not in themselves epidemiologic proof of such
connections.
Analytical observational studies involve the collection of often detailed data in order to make
comparisons of exposure and disease in populations. The simplest type is a cross-sectional study. A
cross-sectional or prevalence study is performed at a single point in time to compare the risk for disease
in unexposed and exposed populations or the risk for exposure in diseased and well populations. Again,
cross-sectional studies can only suggest an association since these studies are done at a single point in
time, the temporal relationship is not known, specifically, whether the exposure came before and thus
caused the disease, or came after and is not truly associated. As such, cross-sectional studies are
considered to be hypothesis-generating rather than able to prove an etiologic hypothesis.
A more complicated study, which can suggest an association more strongly, is the case control
study in which persons with the disease (the cases) and without the disease (controls) are investigated
for their different risk of reported exposures. If the exposure is associated with the disease, then the
cases will be more likely to report this exposure in the past than the controls. Cohort studies are
considered the sine qua non of analytical observational studies. In cohort studies, a group of people
(the cohort) is followed in time, distinguished by their exposure (usually exposed and nonexposed),
and examined for the diseases which develop over time. The population can be followed into the future
in a prospective cohort study or evaluated in the past based on existing records in a retrospective cohort
study. If a particular exposure is associated with a particular disease, then the exposed group would
be expected to have many more cases of the particular disease than the nonexposed group.
The experimental equivalent of a toxicologic study (i.e., controlled laboratory studies in animals)
in epidemiology is the experimental or intervention study. In a clinical trial, a group of people who are
randomly assigned to receive either a particular exposure (usually medication) or not (the placebo),
are followed to observe the effect of the exposure or the lack of the exposure. This type of epidemiologic
study is rarely performed in the study of toxic exposures in humans for obvious ethical reasons.
However, intervention studies which remove or mitigate a toxic exposure, then follow the population
for disease reduction, can be performed.
21.4 EXPOSURE ISSUES
In order to evaluate an exposure–disease association in epidemiology, the exposure of interest must
be defined. In the workplace, this has traditionally taken place by indirect means such as using a job
title as a surrogate for exposure (e.g., a “pipefitter” means asbestos exposure) and more recently, by
using actual workplace air measurements (both room and personal monitoring). However, these
exposure measures are inadequate estimations of the dose received by a particular individual. More
recently, biomonitoring (such as blood lead levels) is being used to give more accurate measures of
individual exposure. These biomarkers of exposure are not without problems since the correlation of
disease with many biomarkers has not been established.
The routes of exposure can determine both the presence and/or the type of human health effect.
Toxic exposures in the occupational setting are generally through inhalation and/or through the skin,
whereas community exposures are predominantly through contaminated water (such as at Woburn,
Massachusetts) and/or the food chain (such as fish consumption at Minamata Bay, Japan). In