Generally, with a linear driver and a single 4.2v lion yes, it is safe. When you will notice dimming definitely depends on the driver, the drive current, the led, and to a lesser extent the battery. Some Cree LED’s have forward voltages as high as ~3.7 volts at high drive currents and there is also some voltage drop through the driver. When the cell gets below the voltage required to keep the output “in regulation” you’ll probably start noticing a reduction in output. Panasonic cells (like the NCR18650B) can safely be drained to a minimum level of 2.5 volts, other manufacturers recommend termination at 2.8v or so with their cells. There are LED’s like the Nichia 219C that have a very low forward voltage, like ~3.3 volts at 3 amps. You’d still notice a reduction in output on HIGH when the battery was sub 3v though I’m sure, although if the driver only ever drove the LED at 350mA… or you generally only operated it in a low mode, well then you might not notice dimming until the battery was very low.
That said, I have a FourSevens mini MLR2 (XP-G2) that I EDC with an RCR CR2 (15266) in it, which isn’t recommended by 47’s but works fine and is super bright compared to primaries. It will however drain the battery to sub 2v, which I’ve done a few times without noticing all too much until the light refuses to change from medium to high mode. It probably has a “buck-boost” driver in it. I “revived” the battery with a 100mA charge which is as low as my RC charger goes. Still using the cell. :-x
Years ago the RC and flashlight community used to be very cautious and recommend discharge levels only down to 3.4v and such, but now adays no one is too concerned with draining down to 2.8v or even 2.5v depending on the cell. I tend to keep my EDC cells pretty topped off though just for maximum output and capacity.