Application of the risk assessment paradigm to the induction of allergic contact dermatitis.

The National Academy of Science (NAS) risk assessment paradigm has been widely accepted as a framework for estimating risk from exposure to environmental chemicals (NAS, 1983). Within this framework, quantitative risk assessments (QRAs) serve as the cornerstone of health-based exposure limits, and have been used routinely for both cancer and noncancer endpoints. These methods have focused primarily on the extrapolation of data from laboratory animals to establish acceptable levels of exposure for humans. For health effects associated with a threshold, uncertainty and variability inherent in the extrapolation process is generally dealt with by the application of "uncertainty factors (UFs)." The adaptation of QRA methods to address skin sensitization is a natural and desirable extension of current practices. Based on our chemical, cellular and molecular understanding of the induction of allergic contact dermatitis, one can conduct a QRA using established methods of identifying a NOAEL (No Observed Adverse Effect Level) or other point of departure, and applying appropriate UFs. This paper describes the application of the NAS paradigm to characterize risks from human exposure to skin sensitizers; consequently, this method can also be used to establish an exposure level for skin allergens that does not present an appreciable risk of sensitization.