sphere is shorter and its ozone depleting potential is insignificant. HFC-134a is used in refrigeration and air conditioning systems, as a blowing agent for polyurethane foams, and as a propellant for medical aerosols. Yearly production is estimated at 175,000 tons. HFC-134a is a colorless gas with a faint ethereal odor that may go unnoticed by most individuals.
HFC-134a has a very low acute inhalation toxicity. Both uptake and elimination are rapid, but uptake is low, and most of the compound is exhaled unchanged. Consequences of acute HFC-134a inhalation have been studied with human subjects and several animal species, including the monkey, dog, rat, and mouse. Considerable inhalation data from controlled studies with healthy human subjects as well as patients with respiratory diseases are available. Studies addressing repeated and chronic exposures, genotoxicity, carcinogenicity, neurotoxicity, and cardiac sensitization were also available. At high concentrations, halogenated hydrocarbons may produce cardiac arrhythmias; this end point was considered in development of AEGL values.
Adequate data were available for development of the three AEGL classifications. Inadequate data were available for determination of the relationship between concentration and time for a fixed effect. Based on the observations that (1) blood concentrations in humans rapidly approach equilibrium with negligible metabolism and tissue uptake and (2) the end point of cardiac sensitization is a blood-concentration related threshold phenomenon, the same concentration was used across all AEGL time periods for the respective AEGL classifications.
The AEGL-1 concentration was based on a 1-hour (h) no-effect concentration of 8,000 parts per million (ppm) in healthy human subjects (Emmen et al. 2000). This concentration was without effects on pulmonary function, respiratory parameters, the eyes (irritation), or the cardiovascular system. Because this concentration is considerably below that causing any adverse effect in animal studies, an intraspecies uncertainty factor (UF) of 1 was applied. The intraspecies UF of 1 is supported by the absence of adverse effects in therapy tests with patients with severe chronic obstructive pulmonary disease and adult and pediatric asthmatics who were tested with metered-dose inhalers containing HFC-134a as the propellant. Because blood concentrations in this study approached equilibrium following 55 minutes (min) of exposure and effects are determined by blood concentrations, the value of 8,000 ppm was made equivalent across all time periods. The AEGL-1 of 8,000 ppm is supported by the absence of adverse effects in experimental animals that inhaled considerably higher concentrations. No adverse effects were observed in rats exposed at 81,000 ppm for 4 h (Silber and Kennedy 1979) or in rats exposed