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HYDROFLUOROCARBON-404A 65 HFC-134a. HFC-134a was tested in four Ames assays for bacterial mutagenesis in Salmonella strains TA98, TA100, TA1535, TA1537, and TA1538 and E. coli strain WP2uvrA (Brusick 1976, as cited in ECETOC 1995; Longstaff et al. 1984; Callander and Priestley 1990, as cited in ECETOC 1995; Araki 1991, as cited in ECETOC 1995; Collins et al. 1995). HFC-134a was also tested for yeast mutagenesis in Saccharomyces cerevisiae (Brusick 1976, as cited in ECETOC 1995); it was nongenotoxic in all studies even when concentrations were as high as 1,000,000 ppm in some assays. At test atmospheres of more than 90%, inhibition of growth was observed (Collins et al. 1995). No abnormalities were observed in chromosomal-aberration studies using either human lymphocytes (Mackay 1990 cited in ECETOC 1995) or Chinese hamster lung cells (Asakura 1991, as cited in ECETOC 1995) at concentrations up to 1,000,000 ppm. Toxicity was observed in cultured human lymphocytes at atmospheres of more than 75% at the 96-hr sampling time (Collins et al. 1995). HFC-134a was inactive in a cell-transformation assay using BHK21 cultures (Longstaff et al. 1984). HFC-134a was not clastogenic in an in vivo mouse micronucleus assay, where male and female mice were exposed for 6 hr at concentrations up to 500,000 ppm (Müller and Hofmann 1989, as cited in ECETOC 1995). HFC-134a did not induce unscheduled DNA synthesis in male rats following exposure for 6 hr at concentrations as high as 100,000 ppm (Trueman 1990, as cited in ECETOC 1995). When male rats were exposed at concentrations up to 50,000 ppm for 6 hr in a single exposure or for 5 consecutive days for bone- marrow cytogenetic evaluation (Anderson and Richardson 1979, as cited in ECETOC 1995), there was no statistically significant increase in total chromosomal aberrations. In a dominant lethal assay, male mice were exposed 6 hr per day for 5 consecutive days at concentrations as high as 50,000 ppm (Hodge et al. 1979b). Males were mated with unexposed virgin females at weekly intervals for several weeks. HFC-134a did not affect fertility or cause mutagenic effects. Carcinogenicity Several chronic studies have been conducted with HFC-134a. In 1996, the NRC reviewed one oral study (Longstaff et al. 1984) and one inhalation study (Hext and Parr-Dobrzanski 1993). In the study by Longstaff et al. (1984), rats were orally administered HFC-134a in corn oil at a dose of 300 mg/kg of body weight per day for 5 days per week for 52 weeks. There was no significant increase in incidence of neoplasms in any organ in the HFC-
