Toxicokinetics and Risk Assessment

Lipscomb, John C.; Ohanian, Edward V.

Overview of the Approach to Noncancer Risk Assessment o Guidance for the Development of Chemical Specific Adjustment Factors: Integration with Mode of Action Frameworks o Derivation and Modeling of Mechanistic Data for Use in Risk Assessment o Empirically Observed Distributions of Pharmacokinetic and Pharmacodynamic Variability in Humans-Implications for the Derivation of Single Point Component Uncertainty Factors Providing Equivalent Protection as Existing RFDs o Use of Classical Pharmacokinetic Evaluations in Drug Development and Safety Assessment o Considerations for Applying Physiologically Based Pharmacokinetic Models in Risk Assessment o Considerations of Design and Data when Developing Physiologically Based Pharmacokinetic Models o In Silico Predictions of Partition Coefficients for Physiologically Based Pharmacokinetic Models o In Vitro to In Vivo Extrapolation of Metabolic Rate Constants for Physiologically Based Pharmacokinetic Models o Use of Physiologically Based Pharmacokinetic Modeling to Evaluate Implications of Human Variability o Developmental Aspects of Children's Pharmacokinetics o Sensitive Populations and Risk Assessment o Statistical Issues in Physiologically Based Pharmacokinetic Modeling o Drug Development and the Use of Pharmacokinetics/Toxicokinetics in Selecting the First Dose of Systemically Administered Drugs in Humans-A Nonclinical Perspective o Pharmacokinetic/PBPK Models in IRIS Assessments