Keywords: benchmark dose, extrapolation, NOAEL, reference dose, safety assessment, variability, health risk assessment, negligible risk, uncertainty management, hazardous substances, exposure, toxic substances
Managing uncertainty in health risk assessment
The process of risk (safety) assessment used to determine negligible-risk levels of human exposure to toxicants is subject to a number of sources of uncertainty. In addition to the common uncertainties related to high-to-low-dose extrapolation, interspecies extrapolation and intraspecies extrapolation, there can be uncertainty associated with extrapolation to alternative routes and durations of exposure. Sampling variation is an important source of uncertainty. It is essential that the various sources of uncertainty be taken into account in the risk and exposure extrapolations, but the total uncertainty should be managed in such a way as to avoid setting overly conservative safe exposures. This article discusses a unifying benchmark-dose approach to risk assessment for carcinogenic and noncarcinogenic health effects, and describes a formal quantitative procedure for managing uncertainty that is less conservative than the common practice of reducing a point of departure on a dose-response curve by a product of uncertainty factors to achieve a safe level of exposure.