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In cardiac sensitization studies in dogs, the test substance was found to have no potential to cause cardiac sensitization in beagle dogs at concentrations up to 30% in air or 50% in air with auxiliary oxygen. There were no positive responses, no questionable positive responses, and no ventricular tachycardia ectopic bursts.

Neuro-behavioral and physiological effects of the test substance were examined in 6 male volunteers. Individuals were exposed to 10, 20, 40, or 60% of the test substance at escalating concentrations administered as 8 pulses of 3 minutes each, with 2-minute clearance periods between each pulse. The first subject exposed to the test substance completed the 8 pulses, but experienced an anesthetic effect and nausea at 60%. Although other physiologic parameters remained stable, the subject’s response was considered intolerable. The second subject to inhale 40% of the test substance experienced discomfort after 1 minute, and requested discontinuation of exposure. Both the 40 and 60% levels were then dropped from further evaluation. The remaining 4 subjects tolerated the 30% level of the test substance. Therefore, 30% was considered to be the MTC (maximum tolerated dose).  At 30% subjects reported anesthetic effects, but no effects were noted in blood pressure, heart rate or rhythm, oxygenation, respiratory rate, temperature, end tidal CO2, or serum chemistries. However, when one subject received the 30% concentration during an NMR imaging study, an anesthetic effect with intolerable hyperacusis was demonstrated.