Acute neurobehavioral effects in rats from exposure to HFC 134a or CFC 12.
1,1,1,2-Tetrafluoroethane (HFC 134a), a chlorine-free hydrofluoroalkane, is internationally replacing billions of pounds of dichlorodifluoromethane (CFC 12) for coolant, refrigerant and aerosol propellant applications. The ALC50 for HFC 134a in rats is 567,000 ppm for 4 h; its potential for cardiac epinephrine sensitization in beagle dogs is acceptable (75,000 ppm); and its capacity to induce carcinogenicity or developmental disorders in animals is minimal. HFC 134a, with a serum half life estimated at 4-11 min, has been accepted for use as a propellant in metered-dose inhalant products, implying a low human toxicity risk from periodic brief exposures. There has been little published human or animal research evaluating possible neurobehavioral toxicity from longer HFC 134a exposures, as may be expected to occur in operational scenarios. In this study, male Wistar rats were exposed to various concentrations of HFC 134a or CFC 12 for up to 30 min while performing in either a rotarod/motorized running wheel apparatus or in an operant chamber The relative neurobehavioral toxicity of CFC 12 and its ozone-depleting substance replacement HFC 134a was assessed by comparing both gross motor system incapacitation and more subtle changes in ability to perform an operant discrimination task. It was shown that exposure to HFC 134a or CFC 12 concentrations from 40,000 to 470,000 ppm, for up to 30 min, induced neurobehavioral deficits in every subject, ranging from reduced operant efficiency to apparent anesthesia. For neurobehavioral endpoints examined in these experiments, HFC 134a inhalation was shown to induce deficits more rapidly, and at lower concentrations when compared to CFC 12 exposure.
Ritchie
G D
GD
Geo-Centers, Inc., Wright-Patterson Air Force Base (WPAFB), OH 45433-7903, USA. glenn.ritchie@wpafb.af.mil
Kimmel
E C
EC
Bowen
L E
LE
Reboulet
J E
JE
Rossi
J
J
D000280:Administration, Inhalation; D000758:Anesthesia; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001522:Behavior, Animal / Q000187:drug effects*; D005617:Chlorofluorocarbons, Methane / Q000633:toxicity*; D003216:Conditioning, Operant / Q000187:drug effects; D006845:Hydrocarbons, Fluorinated / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000523:psychology*; D010100:Oxygen / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D004980:Ethane / Q000031:analogs & derivatives; D005466:Fluorocarbons
D005617:Chlorofluorocarbons, Methane; D006845:Hydrocarbons, Fluorinated; D010100:Oxygen; C063006:norflurane; D004980:Ethane; D005466:Fluorocarbons; C007782:dichlorodifluoromethane