A. Vinegar et Gw. Jepson, CARDIAC SENSITIZATION THRESHOLDS OF HALON REPLACEMENT CHEMICALS PREDICTED IN HUMANS BY PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODELING, Risk analysis, 16(4), 1996, pp. 571-579
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.