PRINCIPLES OF TOXICOLOGY

438 RISK ASSESSMENT
18.1 RISK ASSESSMENT BASICS
A Basic Risk Assessment Paradigm
In 1983, the National Research Council described risk assessment as a four-step analytical process
consisting of hazard identification, dose-response assessment, exposure assessment, and risk characterization.
These fundamental steps have achieved a measure of universal acceptance and provide a
logical framework to assemble information on the situation of potential concern and provide risk
information to inform decision making (see Figure 18.1). The process is rigid enough to provide some
methodological consistency that promotes the reliability, utility, and credibility of risk assessment
outcomes, while at the same time allowing for flexibility and judgment by the risk assessor to address
an endless variety of risk scenarios. Each step in the four-step process known as risk assessment is
briefly discussed below.
Step 1: Hazard Identification. The process of determining whether exposure to a chemical agent,
under any exposure condition, can cause an increase in the incidence or severity of an adverse health
effect (cancer, birth defect, neurotoxicity, etc.). Although the matter of whether a chemical can, under
any exposure condition, cause cancer or other adverse health effect is theoretically a yes/no question,
there are few chemicals for which the human data are definitive. Therefore, not only epidemiological
studies but also laboratory animal studies, in vitro tests, and structural and mechanistic comparability
to other known chemical hazards are considered. This step is common to qualitative and quantitative
risk assessment.
Step 2: Dose–Response Assessment. The process of characterizing the relationship between the
dose of a chemical and the incidence or severity of an adverse health effect in the exposed population.
A dose–response assessment factors in not only the magnitude, duration, and frequency of exposure
but also other potential response-modifying variables such as age, sex, and certain lifestyle factors.
A dose–response assessment frequently requires extrapolation from high to low doses and from
animals to humans.
Figure 18.1 Elements of risk assessment and risk management. Risk assessment provides a means to organize
and interpret research data in order to inform decisions regarding human and environmental health. Through the
risk assessment process, important data gaps and research needs are often identified, assisting in the prioritization
of basic and applied toxicological research. [Adapted from NRC (1983).]