Toxicological evaluation of 1,1,1,2,2-pentafluoroethane (HFC-125).
Acute, subacute, and subchronic inhalation toxicity studies, developmental toxicity studies, a cardiac sensitization evaluation, and mutagenicity assays were conducted with pentafluoroethane (HFC-125). In the acute study, rats were exposed to a single concentration of 800,000 ppm for 4 hr. Ataxic gait and abnormal respiration were observed during exposure but not after exposure. There was no mortality or other signs of toxicity. Repeated exposures of rats to 50,000 ppm, 6 hr/day, 5 days/week for either 4 or 13 weeks elicited no effects on body weight, food consumption, clinical signs, hematology, biochemistry, urinalysis, organ weight, or tissue morphology. Positive evidence of cardiac sensitization in response to an intravenous epinephrine challenge in dogs was seen at 100,000 ppm and above, but not at 75,000 ppm. HFC-125 was not mutagenic in Salmonella typhimurium and Escherichia coli strains at concentrations of 20 to 100% (v/v) with and without activation. No evidence of clastogenic activity was observed in cultured Chinese hamster ovary (CHO) cells or human lymphocytes at < or = 70% HFC-125 when treatments were conducted for 3-4 hr with activation or for 24 and 48 hr (human lymphocytes only) without activation. However, a statistically significant increase in chromosomally aberrant cells was observed in CHO cells at 60% HFC-125 when treatment without activation was extended to 48 hr. The biological significance of this effect is questionable since signs of severe toxicity were also present. In vivo, no micronuclei were induced in mouse bone marrow at concentrations as high as 600,000 ppm HFC-125 for a 6-hr exposure. In addition, HFC-125 did not induce embryotoxic or teratogenic effects in either the rat or the rabbit at exposure concentrations as high as 50,000 ppm.
Kawano
T
T
Daikin Industries, Ltd., Osaka, Japan.
Trochimowicz
H J
HJ
Malinverno
G
G
Rusch
G M
GM
D000014:Abnormalities, Drug-Induced; D000280:Administration, Inhalation; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow; D016466:CHO Cells / Q000187:drug effects; D006224:Cricetinae; D004285:Dogs; D005314:Embryonic and Fetal Development / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D005466:Fluorocarbons / Q000008:administration & dosage / Q000633:toxicity*; D006321:Heart / Q000187:drug effects; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects; D018675:Toxicity Tests
D005466:Fluorocarbons; C078256:pentafluoroethane