Hi,
It's certainly easier to have a single rail.

I've actually never used I2C so my practical knowledege is very limitied but the manual says:
The timing of the I2C instructions is set so that standard speed devices(100kHz) will be accessible at clock speeds up to 8MHz. Fast mode devices (400kHz) may be used up to 20MHz. If it is desired to access a standard speed device at above 8MHz, the following DEFINE should be added to the program:
DEFINE I2C_SLOW 1
It's a bit unclear what happens with the I2C clock at speeds over 20MHz, will it still be 100/400kHz?
Since it's a synchronous protocol I would think it's not overly sensitive to the clock jitter caused by executing the command while the interrupt is active in the background but I don't know. On the other hand, 12bytes at 100kHz is about a 1ms. I guess you could squeeze that in between two DMX packets without too much impact on overall throughput.

/Henrik.