PBPK MODELING OF SHORT-TERM (0 TO 5 MIN) HUMAN INHALATION EXPOSURES TO HALOGENATED HYDROCARBONS

Allowable human exposure to Halons and Halon replacement chemicals is often regulated on the basis of cardiac sensitization potential. Exposure guidelines are established using dose-response data obtained from animal testing. Results from animal tests are often summarized by no-observable-adverse-effect level and lowest-observable-adverseeffect level values. This threshold approach alone does not provide the information necessary to evaluate the cardiac sensitization potential for the chemical of interest under a variety of exposure concentrations and durations. In order to provide a tool for decision makers and regulators tasked with setting exposure guidelines for Halon replacement chem icals, a quantitative approach was established that allows exposures to be assessed in terms of the chemical concentrations in blood during the exposure. A physiologically based pharmacokinetic model was modified to include a respiratory-tract compartment containing a dead-space region and a pulmonary exchange area. The ...