LIMITING THE UNCERTAINTY IN RISK ASSESSMENT BY THE DEVELOPMENT OF PHYSIOLOGICALLY-BASED PHARMACOKINETIC AND PHARMACODYNAMIC MODELS

Analysis of the default cancer risk assessment methodology suggests that the confidence interval usually associated with the prediction of an upper bound on risk underestimates the uncertainty in the risk estimate. This underestimate of uncertainty is based on the use of a large number of policy decisions or professional judgements that are incorporated into the methodology as exact values with no estimate of error. An alternative approach is to develop a comprehensive biologically based risk assessment that provides scientific data to substitute for many of the policy decisions of the default methodology.