Subchronic toxicity and teratogenicity of 2-chloro-1,1,1,2-tetrafluoroethane (HCFC-124).
Inhalation studies were conducted to determine the potential toxicity of HCFC-124. Groups of rats and mice were exposed to HCFC-124 6 hr/day, 5 days/week for 13 weeks at 0, 5000, 15,000, and 50,000 ppm. Subgroups of rats and mice were held for a 1-month recovery period. A functional observational battery (FOB) was conducted on rats at 0, 4, 13, and 16 weeks. Clinical pathology evaluations were conducted at 7, 13, and 17 weeks. Thirteen or 17 weeks after study initiation, rats and mice underwent gross and microscopic evaluation, and livers were evaluated for hepatic beta-oxidation activity. In addition, groups of female rats and rabbits were exposed to HCFC-124 by inhalation during gestation to 0, 5000, 15,000, or 50,000 ppm. Exposure of rats and mice to HCFC-124 caused minimal compound-related effects. Compound-related changes occurred in several clinical pathology parameters in rats and mice. Hepatic beta-oxidation activity was significantly higher in 5000, 15,000, and 50,000 ppm male mice; however, there were no compound-related effects on beta-oxidation activity in rats. During the daily exposures, rats, mice, and rabbits exposed to 50,000 ppm were less responsive to auditory stimuli or less active compared to controls. At the 13-week FOB, male rats exposed to 15,000 or 50,000 ppm had decreased arousal. There were no compound-related effects on mortality, clinical signs, ocular tissues, hematology parameters, organ weights, and tissue morphology at any concentration in rats or mice. Maternal toxicity in rats was evident by a significant decrease in weight gain and food consumption at 50,000 ppm. Similarly, 50,000 ppm pregnant rabbits had lower food consumption. However, for both rats and rabbits, there was no evidence of fetal toxicity at any concentration.
Malley
L A
LA
E. I. du Pont de Nemours and Company, Haskell Laboratory for Toxicology and Industrial Medicine, Newark, Delaware 19714, USA.
Carakostas
M
M
Elliott
G S
GS
Alvarez
L
L
Schroeder
R E
RE
Frame
S R
SR
Van Pelt
C
C
Trochimowicz
H J
HJ
Rusch
G M
GM
D000280:Administration, Inhalation; D000818:Animals; D064227:Chlorofluorocarbons, Ethane; D005617:Chlorofluorocarbons, Methane / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008830:Microbodies / Q000378:metabolism; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D013723:Teratogens / Q000633:toxicity*
D064227:Chlorofluorocarbons, Ethane; D005617:Chlorofluorocarbons, Methane; D013723:Teratogens; C072959:1,1,1,2-tetrafluoro-2-chloroethane