"Adrenaline solutions were prepared immediately prior to each exposure session from a stock solution (Adrenaline 1: 1000, Batch 310002, Phoenix Pharmaceuticals, Gloucester, England) and sterile pyrogen-free water (Formulation Department, Huntingdon Research Centre, Huntingdon, Cambridgeshire, England). Injections were given at a rate of 0.1 mL/sec . Appropriate dilutions were used such that the volume of adrenaline solution used was consistently 0.1 mL/kg bodyweight. The standard lead II electrocardiogram was used throughout the study. Appropriate areas on the dog's limbs were shaved and a conduction medium applied. Standard ECG limb leads were then connected to the prepared areas on the dog with blunt clips. The electrocardiograph (Devices 3442 ECG amplifier with a two-channel chart recorder) was calibrated with 1 mV peaks. The electrocardiogram was then checked for clarity before dosing commenced. A schedule of time and events follow.

Time(min)/Event

0/Start ECG recording

2/First adrenaline challenge administered

7/Test gas supplied to dog

12/Second adrenaline challenge administered Test gas supply discontinued

17/Stop ECG recording"

"The study was carried out in 3 stages. In Stage 1, each of the 9 dogs on the study was tested with fresh air only supplied to the face mask. Various concentrations of adrenaline solution were used in order to establish the response of each individual dog to adrenaline alone. An appropriate initial adrenaline dose was selected for each dog following review of the results. The dogs were then assigned to treatments for use in Stages 2 and 3 of the study. In Stage 2, two dogs were selected for exposure to CFC 11. The purpose of these exposures was to show that the experimental model used gave a positive response with CFC 11, a known cardiac sensitizer. In the initial design of Stage 3, each of the 6 dogs selected for exposures was tested receiving air only for 17 minutes. At this point the adrenaline response of each dog was assessed and compared to previously reported responses. Then each of the 6 dogs selected was exposed to the test gas according to the following schedule. However, if an exposure session resulted in fatal ventricular fibrillation, the dogs remaining on study were not exposed at this concentration value."

"At least one calendar day was allowed between each exposure session to allow the dogs to recover. Previous studies with halogenated hydrocarbons indicate this is sufficient time to allow for recovery from test gas exposure. There was a gap of approximately 8 weeks between the end of exposures with CF3I and the start of exposures with C3F7I. Only the surviving 4 dogs from the CF3I exposures were used in the exposures with C3F7I. When a clear positive response was seen in any dog no further exposures were undertaken on that dog with that test gas. It is considered that a positive response would be seen for that dog at higher exposure levels, this was reported as assumed positive (AP). If a dog died as a result of exposure to the test gas, no further exposures at that concentration or higher concentrations were performed. The study was designed to provide information as to any dose level that gave rise to clear signs of test gas-related cardiac sensitization. The criterion for a positive effect was the appearance of a burst of multifocal ventricular ectopic activity (MVEA) or ventricular fibrillation (VF). Ventricular tachycardia alone was not necessarily considered definitive evidence of a positive response."

Male Beagle Dogs