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Suggested Citation:"Cardiac Sensitization." 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-23 30 Clayton et al. (1960) reported an ALC of greater than 200,000 ppm in guinea pigs after a 2-hr exposure to HFC-23. Twelve male albino guinea pigs were exposed at that concentration for 2 hr, and no clinical signs or pathological changes were attributable to HFC-23. Fleming (1945) exposed two male albino guinea pigs to HFC-23 at a concentration of approximately 30,000 ppm for 6 hr. No effects on respiration or weight gain were observed, and no gross or microscopic pathological effects were found when the animals were sacrificed 1 week after exposure. Cardiac Sensitization On the basis of studies in three species that are discussed in this section, HFC-23 has an extremely low cardiac-sensitization potential. These studies were done using a standard epinephrine challenge test similar to that reported by Reinhardt et al. (1971). In all the cardiac-sensitization studies discussed below, supplemental oxygen was given at HFC-23 concentrations of 500,000 ppm and above. Hopkins and Krantz (1968) exposed female mongrel dogs to HFC-23 at 800,000 ppm and found no effect on cardiac automaticity after an intravenous injection of epinephrine. A control injection of epinephrine at 10 µg/kg body weight was given before exposure to HFC-23, and a challenge injection (same dose) was given after a 5- to 10-min exposure period. An electrocardiogram (ECG) was recorded at the beginning of the injection and for at least 60 sec after each epinephrine injection. A formula for measuring the intensity of a myocardial-sensitization response in terms of relative incidence of multifocal ventricular ectopic contractions (RIMVEC) was used to quantitate the electrocardiographic response. The average RIMVEC response following the challenge injection of epinephrine after exposure to HFC-23 was essentially the same as that following the control injection of epinephrine in the five dogs tested. Hardy and Kieran (1993) exposed male beagle dogs to HFC-23 at concentrations ranging from 100,000 to 500,000 ppm and found no evidence of cardiac sensitization after an intravenous injection of epinephrine. A control injection of epinephrine was given before exposure, and a challenge injection (same dose) was given after 5 min of exposure; the exposure continued for an additional 5 min. The dose of epinephrine was calibrated for each dog to produce an acceptable number (about 10) of ectopic ventricular beats. A dose of 12 µg/kg was the maximum dose used. One dog was test

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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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