The fuel will only be needed for a lighter craft in deep space. Getting it up with a high reliability rocket (like Falcon 9) significantly decreases risk.
In principle yes — even just on the grounds that enriched fuel is expensive — but it's a hard thing to prove in advance, hence all the times humans died in a space mission one way or another.
https://en.m.wikipedia.org/wiki/List_of_spaceflight-related_....
Today's rockets are far more reliable, and anything holding nuclear fuel should be the best of the best.
Er, Challenger?