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 regu lated on the basis of cardiac sensitization potential. The dose-respon se data obtained from animal testing are used to determine the no obse rvable adverse effect level (NOAEL) and lowest observable adverse effe ct level (LOAEL) values. This approach alone does not provide the info rmation necessary to evaluate the cardiac sensitization potential for the chemical of interest under a variety of exposure concentrations an d durations. In order to provide a tool for decision-makers and regula tors tasked with setting exposure guidelines for halon replacement che micals, a quantitative approach was established which allowed exposure s to be assessed in terms of the chemical concentrations in blood duri ng the exposure. A physiologically-based pharmacokinetic (PBPK) model was used to simulate blood concentrations of Halon 1301 (bromotrifluor omethane, CF3Br), HFC-125 (pentafluoroethane, CHF2CF3), HFC-227ea (hep tafluoropropane, CF3CHFCF3), HCFC-123 (dichlorotrifluoroethane, CHCl2C F3), 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 duri ng the exposure.