Submarine Exposure Guidance Levels for Selected Hydrofluorocarbons: HFC-236fa, HFC-23,and HFC-404a (2000)
Chapter: Cardiac Sensitization
sure, and a pharmacokinetic analysis was performed. No exposure-related effects of inhalation exposure to HFC-134a on ECG, pulse rate, blood pressure, and lung function were observed compared with air control and CFC-12 reference conditions. The blood concentrations appeared to approach a plateau between 15 and 30 min into the exposure, although some increases were frequently seen at 55 min. Elimination from the body was rapid.
Acute Toxicity and Irritation
In 1996, the NRC found HFC-134a to have low acute toxicity via the inhalation route. The approximate lethal concentration of HFC-134a for a 4-hr exposure in rats was 567,000 ppm (Silber and Kennedy 1979a), and lethality was observed in two of four rats exposed to 750,000 ppm for 30 min (Rissolo and Zapp 1967). In a study published more recently, the 4-hr LC50 value of HFC-134a in rats was reported to be greater than 500,000 ppm (Collins 1984, as cited in ECETOC 1995).
Additional acute inhalation toxicity studies have been published. Alexander and Libretto (1995) conducted acute 1-hr inhalation toxicity tests of HFC-134a in mice, rats, and beagle dogs. No deaths or clinical signs were observed in mice and rats exposed (nose only) to 810,000 ppm (with oxygen supplementation). Dogs exposed (face only) to 160,000 or 320,000 ppm exhibited salivation, head shaking, and struggling, but no mortality. Clinical signs were not observed in dogs exposed to concentrations of 80,000 ppm or lower.
Local irritation and sensitization tests were performed with HFC-134a as either a gas or a liquid. HFC-134a gas was slightly irritating to the eyes of rabbits (Mercier 1990a, as cited in ECETOC 1995), and liquefied HFC-134a was slightly irritating to rabbit skin (Mercier 1989, as cited in ECETOC 1995), although the effect on skin might have been due to local freezing. Liquefied HFC-134a did not cause contact sensitization in guinea pigs (Mercier 1990b, as cited in ECETOC 1995).
Cardiac Sensitization
In 1996, the NRC found HFC-134a to be a weak cardiac sensitizer when tested in two epinephrine challenge tests in dogs (Mullin and Hartgrove 1979; Hardy et al. 1991). On the basis of the Mullin and Hartgrove (1979) study, the NOAEL and LOAEL for HFC-134a were 50,000 ppm and 75,000
