Upgrade the wiring to a heavier gauge, and make sure all wire and track connections are tight. Other than that, there are no more safety considerations than using any other transformer. If getting a multi-throttle transformer, some suggest putting individual fast acting fuses or circuit breakers in line with each transformer output. Connecting Transient Voltage Suppressors across each output will protect the electronics in locomotives and rolling stock from voltage spikes, which fuses will not protect from.
The Lionel Power House 'bricks' cannot be used alone, and need the ZW controller to vary the voltage. The ZW controller package with (2) 135 watt power supplies is the same price as, and has the same power output of, the MRC unit, with the added versatility of giving you variable voltage outputs for accessories as opposed to the fixed voltage output of the MRC unit. More power supplies can be added as the need requires also.
Larry