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Suggested Citation:"Acute Toxicity." National Research Council. 2000. Submarine Exposure Guidance Levels for Selected Hydrofluorocarbons: HFC-236fa, HFC-23,and HFC-404a. Washington, DC: The National Academies Press. doi: 10.17226/9815.
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HYDROFLUOROCARBON-404A 48 Octanol and water partition coefficient: log Pow = 1.48 Conversion factors: 1 ppm = 4.90 mg/m3; 1 mg/m3 = 0.20 ppm Toxicokinetics In a study of male rats exposed to HFC-125 at 10,000 ppm for 6 hr, Harris et al. (1992) demonstrated that HFC-125 is slowly metabolized to trifluoroacetic acid. The rate of metabolism of HFC-125 was shown to be much slower than that of hydrochlorofluorocarbon (HCFC)-124 (2-chloro-1,1,1,2- tetrafluoroethane) or HCFC-123 (2,2-dichloro-1,1,1-trifluoroethane). That finding is consistent with preliminary data (PAFT 1989), as reported by ECETOC (1994), showing that HFC-125 undergoes little uptake and metabolism at exposure concentrations ranging from 1,000 to 50,000 ppm. Another study (Nakayama et al. 1993, as cited in Kawano et al. 1995) reported no detectable increases in plasma or urine fluoride concentrations in rats exposed to HFC-125 at concentrations up to 50,000 ppm for 4 or 13 weeks, which also suggests that metabolism of HFC-125 is low. Wang et al. (1993) reported that HFC-125 stimulates oxygen consumption and the defluorination of 2-chloro-1,1-difluoroethane in hepatic microsomes from phenobarbital treated rabbits. As in the other studies, no metabolism of HFC-125 was detected under the incubation conditions used. Toxicity Information Summaries of the toxicology of HFC-125 have been published by the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC 1994) and Kawano et al. (1995). Acute Toxicity Groups of five male rats were exposed for 4 hr to HFC-125 at concentrations of 504,000 or 710,000 ppm (Panepinto 1990, as cited in ECETOC 1994). There was no mortality or clinical signs, but transient body- weight loss was observed. In another study, rats (five of each sex) were exposed

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 Submarine Exposure Guidance Levels for Selected Hydrofluorocarbons: HFC-236fa, HFC-23,and HFC-404a
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As part of the effort to phase out the use of stratospheric ozone-depleting substances, such as chlorofluorocarbons (CFCs), the U.S. Navy is considering hydrofluorocarbons (HFCs) as replacements for the CFC refrigerants used aboard its submarines. Before using the HFCs, the Navy plans to set emergency exposure guidance levels (EEGLs) and continuous exposure guidance levels (CEGLs) to protect submariners from health effects that could occur as a result of accidental releases or slow leaks.

In this report, the Subcommittee on Exposure Guidance Levels for Selected Hydrofluorocarbons of the National Research Council's (NRC 's) Committee on Toxicology independently reviews the scientific validity of the Navy's proposed 1-hr and 24-hr EEGLs and 90-day CEGLs for two of the candidate refrigerants-HFC-236fa and HFC-404a. In addition, the subcommittee reviews the the EEGLs and CEGL for HFC-23, one of the combustion products of HFC-236fa. This NRC report is intended to aid the Navy in using HFCs safely.

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