TOXICOLOGICAL PROFILE FOR CHROMIUM - Davidborowski.com

CHROMIUM 1552. HEALTH EFFECTSmany biological processes. A simplified scheme reduces the magnitude of cumulative uncertainty. Theadequacy of the model is, therefore, of great importance, and model validation is essential to the use ofPBPK models in risk assessment.PBPK models improve the pharmacokinetic extrapolations used in risk assessments that identify themaximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 1994).PBPK models provide a scientifically sound means to predict the target tissue dose of chemicals inhumans who are exposed to environmental levels (for example, levels that might occur at hazardous wastesites) based on the results of studies where doses were higher or were administered in different species.Figure 2-3 shows a conceptualized representation of a PBPK model.If PBPK models for chromium exist, the overall results and individual models are discussed in thissection in terms of their use in risk assessment, tissue dosimetry, and dose, route, and speciesextrapolations.PBPK models for chromium are discussed below.2.3.5.1 Summary of PBPK Models.One PBPK model for chromium has been published. The O’Flaherty model (O’Flaherty 1993a, 1996)simulates the absorption, distribution, metabolism, elimination, and excretion of chromium(III) andchromium(VI) compounds in the rat. Two kinetic models describing the distribution and clearance ofchromium(III) compounds in humans are described at the end of this section.2.3.5.2 Chromium PBPK Model Comparison.The O’Flaherty model is the only PBPK model available for chromium.