Acute neurobehavioral effects in rats from exposure to HFC 134a or CFC 12

1,1, 1,2-Tetrafluoroethane (HFC 134a), a chlorine-free hydrofluoroalkane, i s 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 card iac epinephrine sensitization in beagle dogs is acceptable (75,000 ppm); an d its capacity to induce carcinogenicity or developmental disorders In anim als is minimal. HF(: 134a, with a serum half-life estimated at 4-11 min, ha s been accepted for use as a propellant in metered-dose inhalant products, implying a low human toxicity risk from per-iodic brief exposures. There ha s been little published human ol animal research evaluating possible neurob ehavioral toxicity from longer HFC 134a exposures, as may be expected to oc cur in operational scenarios. In this study, male Wistar mts were exposed t o various concentrations of HFC: 134a or CFC 12 for up to 30 min while perf orming in either a rotarod/motorized running wheel apparatus or in art oper ant chamber The relative neurobehavioral toxicity of CFC 12 and its ozone-d epleting substance replacement HFC 134a was assessed by comparing both gros s motor system incapacitation and more subtle changes in ability to perform an operant discrimination task. Ii was shown that exposure to HFC 134a oi CFC 12 concentrations from 40,000 to 470,000 ppm, for Icp to 30 min, induce d neurobehavioral deficits in every subject, ranging from reduced operant e fficiency to apparent anesthesia. For neurobehavioral endpoints examined in these experiments, HFC 134a inhalation was shown to induce deficits more r apidly and at lower concentrations when compared to CFC 12 exposure. (C) 20 01 Elsevier Science Inc. All lights reserved.