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 ALC 50 for HFC 134a in rats is 567,000 ppm for 4 h; its potential for cardiac...

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Published in:	Neurotoxicology (Park Forest South) Vol. 22; no. 2; pp. 233 - 248
Main Authors:	Ritchie, Glenn D, Kimmel, Edward C, Bowen, Larry E, Reboulet, James E, Rossi, John
Format:	Journal Article
Language:	English
Published:	Orlando, FL Elsevier B.V 01-04-2001 Elsevier
Subjects:	1,1,1,2-Tetrafluoroethane Administration, Inhalation Anesthesia Animals Atmosphere Exposure Chambers Behavior, Animal - drug effects Biological and medical sciences CFC 12 Chemical and industrial products toxicology. Toxic occupational diseases Chlorofluorocarbons, Methane - toxicity Conditioning, Operant - drug effects dichlorodifluoromethane General pharmacology HFC 134a Hydrocarbons, Fluorinated - toxicity Male Medical sciences Motor Activity - drug effects Neurobehavioral assessment Neurotoxicity Syndromes - psychology Operant conditioning Oxygen - pharmacology Ozone depleting substances Performance deficits Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Rats Rats, Wistar Refrigerants Toxicology Various organic compounds ALC 50: approximate lethal concentration Operant conditioning CFC 12 F+O 2: CFC 12 (Freon 12) with oxygen replacement group CFC 12: dichlorodifluoromethane MSDS: material data safety sheet Neurobehavioral assessment CFC: chlorofluorocarbon LC 50: lethal concentration HLD: hindlimb dysfunction HFC: hydrofluorocarbon HEPA: high efficiency particulate air NC: nitrogen control group FLD: forelimb dysfunction HFC 134a: 1,1,1,2-tetrafluoroethane EEG: electroencephalogram Rats MDI: metered dose inhaler EPA: environmental protection agency Performance deficits REC: recovery R: HFC 134a (R 134a) without oxygen replacement group LOR: loss of righting ODSR: ozone-depleting substance replacement BBB: blood-brain barrier ODS: ozone-depleting substance R+O 2: HFC 134a (R 134a) with oxygen replacement group CNS: central nervous system LOE: loss of equilibrium F: CFC 12 (Freon 12) without oxygen replacement group Ozone depleting substances HFC 134a Refrigerants Rat Motor system disorder Toxicity Learning Acquisition process Motricity Nervous system diseases Pharmaceutical technology Coolant Methane derivatives Acute Rodentia Instrumental conditioning Intrapulmonary administration Ethane derivatives Rotation Propellent Cerebral disorder Inhalation Motility disorder Locomotion Vertebrata Chronic Mammalia Animal Central nervous system disease Fluorine Organic compounds
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Summary:	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 ALC 50 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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0161-813X 1872-9711
DOI:	10.1016/S0161-813X(01)00011-0