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HYDROFLUOROCARBON-23 34 SUMMARY Toxicokinetic studies indicate that HFC-23 is readily absorbed by the lungs and that blood concentrations reach a plateau within minutes. HFC-23 is rapidly eliminated from the blood upon termination of exposure. Table 3-1 summarizes the studies on HFC-23 for cardiac sensitization and Table 3-2 summarizes all the noncancer toxicity studies on HFC-23. The animal toxicity information and human exposure data indicate that HFC-23 has low toxicity. The only significant observations were reduced response to sound in rats exposed at 186,000 ppm and lightheadedness, tingling and numbness of the extremities, and hyperacusis in humans after exposure at 300,000 ppm and above. Cardiac-sensitization studies conducted in three species indicate that HFC-23 has the potential to cause cardiac sensitization at high concentrations. Evidence of such sensitization was observed in baboons and cats exposed at 700,000 ppm, but no evidence was observed in dogs exposed at concentrations as high as 800,000 ppm. A developmental toxicity study in rats exposed to HFC-23 at a concentration of 50,000 ppm reported no evidence of maternal or fetal toxicity or teratogenicity. There is no evidence that HFC-23 is genotoxic. There are no available long-term toxicity studies or carcinogenicity bioassays of HFC-23. TABLE 3-1 Summary of Cardiac Sensitization Studies with HFC-23 Species Concentration, ppm Ventricular Reference Arrhythmia Mongrel dogs 800,000 0/5 Hopkins and Krantz 1968 Beagle dogs 100,000-500,000 0/6 Hardy and Kieran 1993 Baboons 600,000 0/8 Branch et al. 1994 Baboons 700,000 1/8 Branch et al. 1994 Cats 700,000 3/5 Ewing et al. 1990 Cats 700,000 3/7 Branch et al. 1990
HYDROFLUOROCARBON-23 35 TABLE 3-2 Summary of Noncancer Toxicity Information for HFC-23 Species Exposure End Point NOAEL, LOAEL, Reference Frequency ppm ppm and Duration Acute Toxicity Human 3 min, air Central 200,000 300,000 Fagan et 2 min, 8 nervous al. 1995 pulses system effects Rat 4 hr Central 18,900 186,000 Kennedy nervous and Nash system 1980 effects Guinea pig 2 hr No 200,000 ND Clayton significant et al. 1960 effect Guinea pig 6 hr No 30,000 ND Fleming significant 1945 effect Dog 5-10 min Cardiac 800,000 ND Hopkins sensitization and Krantz 1968 Dog 10 min Cardiac 500,000 ND Hardy sensitization and Kieran 1993 Baboon 3 min Cardiac 600,000 700,000 Branch et sensitization al. 1994 Cat 10 min Cardiac ND 700,000 Ewing et sensitization al. 1990 Cat 10 min Cardiac ND 700,000 Branch et sensitization al. 1990 Subchronic Toxicity Rat 6 hr/d, 90 No 10,000 ND Leuschner consecutive significant et al. 1983 d effect Dog 6 hr/d, 90 No 5,000 ND Leuschner consecutive significant et al. 1983 d effect Developmental Toxicity Rat 6 hr/d, Maternal 50,000 ND Munley gestation d toxicity 1997 7-21 Fetal 50,000 ND toxicity Abbreviation: ND, not determined.
