2-Butene, 1,1,1,4,4,4-hexafluoro-, (2Z)-

Specific investigations: other studies

Additional information

A GLP cardiac sensitization study was conducted using a titrated epinephrine challenge study design. A group of 6 male beagle dogs were exposed muzzle-only to vapours of the substance at concentrations of 12500, 25000, or 50000 ppm. Each level was evaluated in the animals with a minimum of 48 hours between each exposure and each dog served as its own control. Three days prior to exposure, a determination was made for the maximum level of epinephrine that would not cause a cardiac arrhythmia for each animal (sub-arrhythmia dose). The dogs were then exposed to the test compound for a total of approximately 33 minutes. After the first five minutes of exposure, each dog received a bolus intravenous injection of predetermined increasing doses of epinephrine up to and including the pre-determined maximum sub-arrhythmia dose. Epinephrine challenge bolus injections were administered a minimum frequency of 3 minutes apart or until the electrocardiogram (ECG) of the animal returned to its normal baseline rhythm. The dogs were monitored for the development of a cardiac arrhythmia. Cardiac arrhythmias were observed in 5 animals following exposure to 50000 ppm of the test substance and in 4 animals following exposure to 25000 ppm of the test substance. There were no signs of cardiac arrhythmia noted in animals that were exposed to 12500 ppm of the test substance. Under the conditions of this study, the no-observed adverse effect concentration (NOAEC) and lowest-observed adverse effect concentration (LOAEC) for cardiac sensitization in epinephrine-challenged dogs were 12500 ppm (83870 mg/m³) and 25000 ppm (1677740 mg/m³), respectively.