Toxicological Sciences, Vol 52, 289-301, Copyright © 1999 by Society of Toxicology
GM Rusch, D Coombs and C Hardy
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.
ARTICLES
The acute, genetic, developmental, and inhalation toxicology of 1,1,1,3,3-pentafluoropropane (HFC 245fa)
AlliedSignal Inc, Morristown, New Jersey 07962-1139, USA. george.rusch@alliedsignal.com
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