The two main factors to be worried about are the overall pressure that is generated by your charge, and the speed in which it reaches that pressure. Either one, if of a sufficient overmatch is more than enough to kill or maim you or other shooters. The third variable is the strength of the barrel and cylinder (assuming a revolver). With proper lab testing or a known pedigree to the metal, it would be possible to find all kinds of propellants that would work, and do so safely. Absent that there are a very limited number of choices that can be safely used without exhaustive precautions to avoid a potential catastrophic failure.
In short the prohibition to avoid smokeless in black powder arms, is to address the 99.999% of uses that people will ever use their firearms for. And in 99.999% of all uses of smokeless powder in a black powder firearm, the shooter is operating with a far smaller safety margin than would be prudent.