Submarine Exposure Guidance Levels for Selected Hydrofluorocarbons: HFC-236fa, HFC-23,and HFC-404a (2000)
Chapter: Exposure Guidance Levels for HFC-125
Exposure Guidance Levels for HFC-125
A summary of the noncancer toxicity studies on HFC-125 is presented in Table 4-2. On the basis of those data, the subcommittee calculated 1-hr and 24-hr EEGLs and a 90-day CEGL for HFC-125. Because the submariner population is all male, young, and healthier than the general population, the subcommittee did not use an uncertainty factor to account for intraspecies variability in its calculations.
To calculate a 1-hr EEGL, the subcommittee used a cardiac sensitization study in dogs, in which the NOAEL was 75,000 ppm (Hardy 1992, as cited in Kawano et al. 1995). Because absorption of hydrofluorocarbons via the inhalation route is rapid, reaching maximal concentrations in the blood within 5 min of exposure and equilibrium within the next 15 min (Azar et al. 1973; Trochimowicz et al. 1974; Mullin et al. 1979), the NOAEL for the 10-min exposure can be used without time extrapolation. The NOAEL was divided by an uncertainty factor of 10 to account for interspecies differences, as no human data are available on HFC-125, to yield a 1-hr EEGL of 7,500 ppm.
For the 24-hr EEGL, the subcommittee used a 4-week toxicity study in rats, in which the highest tested concentration of 50,000 ppm was the NOAEL (Nakayama et al. 1992b, as cited in Kawano et al. 1995). The NOAEL was divided by an uncertainty factor of 10 to extrapolate from animals to humans to yield a 24-hr EEGL of 5,000 ppm.
In a 90-day toxicity study in rats, the highest tested concentration of 50,000 ppm was the NOAEL for the study (Nakayama et al. 1993, as cited in Kawano et al. 1995). That value was divided by an uncertainty factor of 10 to account for interspecies variability, and that value was then multiplied by 1/4 (to account for exposure for 6 hr per day) and by 5/7 (to account for exposure five times per week), which yielded a 90-day CEGL of about 900 ppm.
To calculate the 24-hr EEGL and the 90-day CEGL for HFC-125, the subcommittee used a NOAEL of 50,000 ppm. However, one developmental toxicity study (Master et al. 1992, as cited in Kawano et al. 1995) reported that pregnant rats exhibited an unsteady gait at a concentration of 50,000 ppm. The subcommittee did not use this sign of toxicity for determining the NOAEL, because the exposure guidance levels being developed for the Navy are specifically for use on submarines—vessels with no female crew members. If HFC-125 (or HFC-404a) is used aboard other vessels, the exposure guidance levels should be re-evaluated on the basis of maternal toxicity.
A summary of the toxicology of HFC-134a was published by ECETOC (1995). In addition, the National Research Council published an evaluation
of the toxicity of HFC-134a in a report titled Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 (NRC 1996). Below is a brief description of the toxicity data presented in that evaluation and in new studies on HFC-134a.
TABLE 4-2 Summary of Noncancer Toxicity Information for HFC-125
