Relating Blood Concentration Time Courses To Cardiac Sensitization ThresholdsDuring Inhalation of Halon Replacement Chemicals

摘要

Human exposure to Halon and Halon replacement chemicals is often regulated on thebasis of cardiac sensitization potential. The test results are evaluated in terms of a dose-response curve from which No Observed Adverse Effect Level (NOAEL) and Lowest Observed Adverse Effect Level (LOAEL) values are determined. 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 with allowed exposures to be assessed in terms of the chemical concentration in blood during the exposure. A Physiologically Based Pharmacokinetic (PBPK) model was used to simulate blood concentrations of Halon 1301, FC-3-1-10 (perfluorobutane, C4F10), HCFC-124 (chlorotetrafluoroethane, CHC1FCF3) HFC-125 (pentafluoroethane, CHF2CF3), HFC-227ea (heptafluoropropane, CF3CHFCF3), HFC-23 (trifluoromethane, CHF3), HCFC-22 (chlorodifluoromethane, CHClF2), HCFC-123 (dichlorotrifluoroethane, CHCL2CF3) and CF3I (trifluoroiodomethane) during an inhalation exposure. The inhalation exposure time required to achieve the chemical blood level achieved in the LOAEL cardiac sensitization exposure was calculated for the Halon replacement chemicals. This work demonstrates a quantitative approach for use as a tool in establishing appropriate egress times for people exposed to inhalation of Halon replacement chemicals.