The acute, genetic, developmental, and inhalation toxicology of 1,1,1,3,3-pentafluoropropane (HFC 245fa)

1,1,1,3,3-Pentafluoropropane (HFC 245fa) is a volatile, low boiling liquid. It was inactive in a reverse mutation (Ames) assay using five strains of S almonella typhimurium and one strain of Escherichia coil. It was also inact ive in an in vivo mouse micronucleus assay with exposures of 101,000 ppm. I n a chromosome aberration study with human lymphocytes, some activity was s een when cell cultures were exposed to atmospheres of 30% v/v or higher for 24 h without metabolic activation. No activity was seen in assays using le ss than 30% v/v or exposure times of less than 24 h. No activity was seen i n the presence of metabolic activation even with exposures of 70%. It was n ot toxic by the dermal route. There was no mortality or significant signs o f toxicity when rats and mice were given 4-h exposures to levels of 203,000 ppm or 101,000 ppm of HFC 245fa, respectively. In a cardiac sensitization study with dogs involving intravenous administration of epinephrine, the no observed effect level (NOEL) was 34,000 ppm and the threshold for a respon se was 44,000 ppm. In a rat inhalation, developmental toxicity study, a sli ght reduction in pup weight was seen at 50,000 ppm, but not at 10,000 ppm. There were no developmental effects at any level. A series of three inhalat ion toxicity studies were conducted. All involved daily 6-h exposures up to 50,000 ppm. The first study involved 14 consecutive snout-only exposures. There were no treatment-related effects on body weight, survival, or histol ogic parameters. BUN, GPT, and GOT levels frequently were elevated compared to controls,whereas cholesterol levels: tended to be lower. The second stu dy involved 28 consecutive whole-body exposures. Again, there were no treat ment related effects on body weight, survival, or histological parameters. Urine volume was increased. Increases were also seen in several red blood c ell parameters. These may be related to partial dehydration. Increases were seen in BUN levels and alkaline phosphatase (AP), GPT, GOT and CPK activit ies, primarily in rats exposed at 10,000 and 50,000 ppm. Urinary fluoride l evels were also elevated in an exposure-related pattern. In the third study , whole-body exposures were conducted 5 days per week for 13 weeks, There w ere no treatment-related effects on survival, clinical observations, body w eight gain, or food consumption. Urine volumes were increased, urinary fluo ride levels were elevated, and increases were seen in red blood cell counts , and related parameters and increases were seen in AP, GOT, GPT and CPK ac tivities. These effects were seen in the 10,000 and 50,000 ppm exposure lev el groups. Histopathologic examination did not show any effects on the kidn ey, liver, or lungs. There was an increased incidence of myocarditis in all animals exposed at 50,000 ppm and the majority exposed at 10,000 ppm. It w as described as mild. Based on these findings, 2000 ppm appears to be a no observed adverse effect level.