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 Salmonella typhimurium and one strain of Escherichia coli. It was also inactive in an in vivo mouse micronucleus assay with exposures of 101,000 ppm. In a chromosome aberration study with human lymphocytes, some activity was seen 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 less than 30% v/v or exposure times of less than 24 h. No activity was seen in the presence of metabolic activation even with exposures of 70%. It was not toxic by the dermal route. There was no mortality or significant signs of 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 response was 44,000 ppm. In a rat inhalation, developmental toxicity study, a slight 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 inhalation 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 histologic parameters. BUN, GPT, and GOT levels frequently were elevated compared to controls , whereas cholesterol levels tended to be lower. The second study involved 28 consecutive whole-body exposures. Again, there were no treatment related effects on body weight, survival, or histological parameters. Urine volume was increased. Increases were also seen in several red blood cell parameters. These may be related to partial dehydration. Increases were seen in BUN levels and alkaline phosphatase (AP), GPT, GOT and CPK activities, primarily in rats exposed at 10,000 and 50,000 ppm. Urinary fluoride levels 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 were no treatment-related effects on survival, clinical observations, body weight gain, or food consumption. Urine volumes were increased, urinary fluoride 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 activities. These effects were seen in the 10,000 and 50,000 ppm exposure level groups. Histopathologic examination did not show any effects on the kidney, 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 was described as mild. Based on these findings, 2000 ppm appears to be a no observed adverse effect level.
Rusch
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AlliedSignal Inc, Morristown, New Jersey 07962-1139, USA. george.rusch@alliedsignal.com
Coombs
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Hardy
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D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000280:Administration, Inhalation; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000648:ultrastructure; D002849:Chromatography, Gas; D002869:Chromosome Aberrations / Q000139:chemically induced; D025063:Chromosome Disorders; D004285:Dogs; D004435:Eating / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005459:Fluorides / Q000652:urine; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012871:Skin Diseases / Q000139:chemically induced; D013723:Teratogens / Q000633:toxicity*; D013997:Time Factors; D005466:Fluorocarbons
D004837:Epinephrine; D005459:Fluorides; D006845:Hydrocarbons, Fluorinated; D009153:Mutagens; D013723:Teratogens; C403631:1,1,1,3,3-pentafluoropropane; D005466:Fluorocarbons