ABSTRACT
This chapter addresses the increasing use of pharmacokinetic (PK) and physiologically based PK (PBPK) models in the derivation of reference values for the US Environmental Protection Agency’s (EPA) Integrated Risk Information System (IRIS) Program. It examines use of PK and PBPK models in IRIS assessments to derive reference values, the main quality criteria in the evaluation of a PBPK model intended for use in an assessment, and examples of PK or PBPK models that have been used in IRIS assessments or other US EPA programs. The IRIS database has subsequently become available to risk assessors worldwide, and is a major resource supporting efforts to protect the public health. The US EPA revision of the cancer assessment for dichloromethane was one of the first to incorporate PBPK modeling in the derivation of an inhalation unit risk value. Among biologically based models, PBPK models address the PK differences, and biologically based dose–response models address the pharmacodynamic differences.
