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HYDROFLUOROCARBON-404A 49 (whole body) to HFC-125 at 800,000 ppm for 4 hr (Nakayama et al. 1992a, as cited in Kawano et al. 1995). Oxygen was maintained at 200,000 ppm. No deaths occurred during exposure or during the 14-day post-exposure observation period. Clinical signs observed during exposure included ataxia, decreased locomotor activity, dyspnea, and decreased auditory response. These signs disappeared within 1 hr after exposure. Thus, the 4-hr LC50 value for HFC-125 is considered to be greater than 800,000 ppm. Cardiac Sensitization Male beagle dogs were exposed to HFC-125 at concentrations of 0, 75,000, 100,000, 150,000, 200,000, 250,000, or 300,000 ppm for 10 min. An intravenous injection of epinephrine was administered before and during exposure to HFC-125 (Hardy 1992, as cited in Kawano et al. 1995). If a life- threatening arrhythmia occurred after the challenge injection, the material was considered a cardiac sensitizer at that inhaled concentration. A known cardiac sensitizer (CFC-11) was used as a positive control to validate the system, and Halon 1301 (CF3 Br), also a known cardiac sensitizer, was used to provide comparative data. Positive evidence of cardiac sensitization was seen at 100,000 ppm and greater but not at 75,000 ppm. Therefore, the no-observed-adverse- effect level (NOAEL) for cardiac sensitization was determined to be 75,000 ppm and the lowest-observed-adverse-effect level (LOAEL) was 100,000 ppm. HFC-125 was less potent than CFC-11 but more potent than Halon 1301. Vinegar and Jepson (1995) proposed a quantitative approach for relating blood-concentration time courses to cardiac-sensitization thresholds during inhalation of HFC-125. A physiologically based pharmacokinetic model was used to simulate blood concentrations of HFC-125 in humans during inhalation exposure. The target concentration of HFC-125 in blood was established by simulating a 5-min inhalation exposure at the LOAEL for cardiac sensitization (100,000 ppm). Although the chemical concentration in venous blood does not achieve a steady-state value after 5 min, that exposure period is used in most cardiac-sensitization protocols prior to epinephrine challenge. The blood concentration achieved after 5 min was used as the concentration at which cardiac sensitization was likely to occur. The exposure time required to produce that target level at various concentrations was estimated for resting- and moderate-activity conditions. Results of this study showed that some exposures will not produce the target chemical concentrations in blood no matter how long the exposure occurs, that expo
