Linda S. Mullin

Blood Levels of Fluorocarbon Related to Cardiac Sensitization

Unanesthetized beagle dogs were exposed to concentrations of fluorocarbon-11 and fluorocarbon-12 which had been reported to produce cardiac sensitization. During and after the exposure, arterial and venous blood samples were obtained for fluorocarbon analysis. The blood concentration rose rapidly during the first few minutes of the 10-minute exposure and more slowly thereafter. When the exposure was terminated, there was a rapid initial fall in the blood concentration followed by a more prolonged decline. A definite arterial-venous difference was found. Despite a tenfold difference in the inspired concentration of the two compounds, the blood concentrations associated with cardiac sensitization were similar for both agents. The average blood concentration (µg/ ml) associated with exposure to levels known to sensitize the beagle heart was: 28.6 arterial and 19.7 venous for fluorocarbon-11; and 35.3 arterial and 22.8 venous for flurocarbon-12.

Halogenated Hydrocarbon-Induced Cardiac Arrhythmias Associated with Release of Endogenous Epinephrine

Many unsubstituted and halogenated hydrocarbons have been shown to be capable of sensitizing the mammalian heart to intravenously injected epinephrine, resulting in serious and sometimes fatal cardiac arrhythmias. This experiment was performed to determine if cardiac sensitization could occur in animals in the absence of an exogenous source of epinephrine, as this phenomenon has been alleged to cause sudden deaths in humans in the absence of exogenous epinephrine. Beagle dogs were trained to run on a treadmill to increase their circulating level of epinephrine. While being exercised, they were exposed to fluorocarbon 11, fluorocarbon 12, or fluorocarbon 114, which had been tested previously at Haskell Laboratory and found to be capable of sensitizing the dogs heart to intravenousty injected epinephrine. The results of this study show that, while fluorocarbon 12 and fluorocarbon 114 did produce cardiac sensitization, a much higher concentration was needed to produce this effect than with the intravenous a...

Cardiac arrhythmias and blood levels associated with inhalation of Halon 1301

In this study we determined airborne concentrations of Halon 1301 (CBrF3) and the associated blood levels which produce cardiac arrhythmias in dogs. Beagle dogs were exposed by inhalation to Halon 1301 concentrations ranging from 5 to 20% and, after five minutes of exposure, were given epinephrine by intravenous injection (8--10 micrograms/kg). Electrocardiograms were recorded. Serious cardiac arrhythmias were produced with concentrations of 7.5% or greater. A second group of dogs with cannulas surgically implanted in the common carotid artery and external jugular vein were exposed to 5%, 7.5% and 10% Halon 1301 for 60 minutes. The blood concentration of Halon 1301 increased rapidly during the first five minutes of exposure, plateaued within twenty minutes, and declined rapidly after exposure. The mean blood concentrations at equilibrium were directly proportional to airborne concentrations: at a concentration of 5% in air -- arterial 19.2 micrograms/mL, venous 14.6 micrograms/mL; at 7.5% in air -- arterial 30.6 micrograms/mL, venous 28.4 micrograms/mL; and at 10% in air -- arterial 402 micrograms/mL, venous 32.1 microgram/mL. Since there was no rapid increase in blood fluorocarbon concentration after the first five minutes of exposure, it does not seem likely that risk of cardiac sensitization would increase with increased length of exposure to a given concentration.

Experimental Human Exposures to Fluorocardon 12 (Dichlorodifluoromethane)

The acute toxicity of fluorocarbon 12 was studied as it relates to establishing safe hygienic standards for single, brief exposures. Two human volunteers were exposed to concentrations of 1000 and 10,000 ppm of fluorocarbon 12 for 2.5 hours. They were exposed twice to both concentrations, and on six occasions they were exposed to air. Clinical observations, laboratory tests, subjective impressions, continuous electrocardiogram monitoring, and tests of psychomotor performance did not reveal any adverse effects resulting from exposure to 1000 ppm of fluorocarbon 12. Exposures to 10,000 ppm resulted only in a 7% reduction in the standardized psychomotor test score. These findings suggest that exposure to 10,000 ppm of fluorocarbon 12 for 2.5 hours will not pose a serious threat to an individuals health. Measurement of the subjects’ end-tidal air for fluorocarbon 12 made immediately postexposure and periodically thereafter showed that the compound is rapidly eliminated from the lungs.