Education and Information Division, Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Robert A. Taft Laboratories, 4676 Columbia Parkway, MSC-15, Cincinnati, Ohio 45226, USA
Epidemiologic data is increasingly being used for dose-response
analysis in risk assessment. The Environmental Protection Agency
(EPA) and other U.S. agencies have expressed a preference for
using epidemiologic data rather than toxicologic data when possible.
However, there are a number of important sources of uncertainty
in using epidemiologic data for this purpose that need to be
clearly recognized and, when possible, quantified. This paper
presents a critical review of the major sources of uncertainty
in the use of epidemiologic data for cancer risk assessment.
These may include: (1) study design issues such as potential
confounding and other biases, inadequate sample size, and followup,
(2) the choice of the data set, (3) specification of the dose-response
model, (4) estimation of exposure and dose, and (5) unrecognized
variability in susceptibility. Examples from risk assessments
for cadmium, asbestos, and diesel exhaust are used to illustrate
the potential magnitude of some of these sources of uncertainty.
It is shown that the overall uncertainty from these various
sources combined may often result in highly uncertain risk estimates
from dose-response modeling of epidemiologic data. For this
reason, we believe it is best to present a range of possible
risk estimates, which, to the extent possible, reflects the
variability and uncertainty inherent in the dose-response evaluation
of epidemiologic data.
