Cardiac Sensitization Thresholds of Halon Replacement Chemicals Predicted in Humans by Physiologically-Based Pharmacokinetic Modeling

Human exposure to halons and halon replacement chemicals is often regulated on the basis of cardiac sensitization potential. The dose-response data obtained from animal testing are used to determine the no observable adverse effect level (NOAEL) and lowest observable adverse effect level (LOAEL) values. This 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 chemicals, a quantitative approach was established which allowed exposures to be assessed in terms of the chemical concentrations in blood during the exposure. A physiologically-based pharmacokinetic (PBPK) model was used to simulate blood concentrations of Halon 1301 (bromotrifluoromethane, CF₃Br), HFC-125 (pentafluoroethane, CHF₂CF₃), HFC-227ea (heptafluoropropane, CF₃CHFCF₃), HCFC-123 (dichlorotrifluoroethane, CHCl₂CF₃), and CF₃I (trifluoroiodomethane) during inhalation exposures. This work demonstrates a quantitative approach for use in linking chemical inhalation exposures to the levels of chemical in blood achieved during the exposure.