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HYDROFLUOROCARBON-404A 61 ppm, respectively. The Hardy et al. (1991) study indicated a NOAEL of 40,000 ppm and a LOAEL of 80,000 ppm. The EC50 value for cardiac sensitization for HFC-134a was found to be 270,000 ppm (ICI Chemicals and Polymers 1991, as cited in AIHA 1991). Subchronic Toxicity Three subchronic inhalation toxicity studies (Silber and Kennedy 1979b; Riley et al. 1979; Hext 1989) were considered in the NRC's earlier evaluation of HFC-134a (NRC 1996). Male rats exposed to HFC-134a at a concentration of 100,000 ppm for 6 hr per day, 5 days per week for 2 weeks had increased respiratory rate and increased urine fluoride levels, but there were no alterations in body weight, organ weight, clinical pathology, or tissue histopathology (Silber and Kennedy 1979b). Riley et al. (1979) exposed rats (16 of each sex per group) to HFC-134a at 0, 1,000, 10,000, or 50,000 ppm for 6 hr per day, 5 days per week for 4 weeks. Minor changes were observed in liver, kidney, and testes weights at 50,000 ppm and 10,000 ppm (liver only), but there were no histopathological changes in these organs. A slight focal interstitial pneumonia was observed in the male rats of the 50,000-ppm group. Clinical observations, body weights, and clinical pathology were normal. The NRC also reviewed an unpublished inhalation study by Hext (1989), which was subsequently published by Collins et al. (1995). In this study, groups of rats (20 males and 20 females) were exposed to HFC-134a at 0, 2,000, 10,000, or 50,000 ppm for 6 hr per day, 5 days per week for 13 weeks. Biological end points evaluated were clinical observations, body weights, food consumption, organ weights, clinical pathology, and tissue histopathology. No exposure-related effects were observed. Additional subchronic inhalation studies were also evaluated by the subcommittee. In a 90-day study with mice exposed (nose only) to HFC-134a at concentrations up to 50,000 ppm for 1 hr per day, no clinical signs of toxicity and no alteration in body-weight gains were observed (Alexander and Libretto 1995). Similarly, no clinical signs or effects on weight gains were observed in rats exposed daily for 1 hr to HFC-134a at 2,500, 15,000, or 50,000 ppm for 50 weeks (Alexander and Libretto 1995). Alexander and Libretto (1995) also conducted two separate 1-year inhalation toxicity studies of HFC-134a in dogs using different delivery systems. In one study, dogs received 120,000 ppm for 1 hr per day via a face- mask inhalation delivery system. In the other study, pulse concentrations of up to 2.25 grams were administered twice a day with a metered-concentration