ABSTRACT
This chapter deals with new estimates of the uncertainty in pharmacokinetic (PK) versus pharmacodynamic (PD) variability. Perfect information is modeled by reducing to zero the uncertainty in one or both of these variability estimates for the sample reference doses chemicals within the straw man risk simulation system. In the International Programme on Chemical Safety (IPCS) framework, chemical-specific adjustment factors are intended to be used in place of the traditional 10-fold factors when there is a judgment that enough suitable quantitative toxicokinetic and/or toxicodynamic data are available. The various PK and PD components of interindividual variability in susceptibility act multiplicatively to determine individual susceptibility. An important innovation in the IPCS framework is a split of each of the traditional interspecies and interindividual variability uncertainty factors between PK and PD components. The “value” of a particular piece of new information depends on the “baseline” or “prior” uncertainty in the measured parameter in the absence of the added information.
